Ross & Wilson Anatomy and Physiology in Health and Illness (32 page)

explain why polycythaemia occurs.

Anaemias

In anaemia there is not enough haemoglobin available to carry sufficient oxygen from the lungs to supply the needs of the tissues. It occurs when the rate of production of mature cells entering the blood from the red bone marrow does not keep pace with the rate of haemolysis. The classification of anaemia is based on the cause:

•
impaired erythrocyte production

    
–
iron deficiency

    
–
megaloblastic anaemias

    
–
hypoplastic anaemia

•
increased erythrocyte loss

    
–
haemolytic anaemias

    
–
normocytic anaemia.

Anaemia can cause abnormal changes in red cell size or colour, detectable microscopically. Characteristic changes are listed in
Table 4.4
. Signs and symptoms of anaemia relate to the inability of the blood to supply body cells with enough oxygen, and may represent adaptive measures. Examples include:

•
tachycardia; the heart rate increases to improve blood supply and speed up circulation

•
palpitations (an awareness of the heartbeat), or angina pectoris (
p. 119
); these are caused by the increased effort of the overworked heart muscle

•
breathlessness on exertion; when oxygen requirements increase, respiratory rate and effort rise in an effort to meet the greater demand.

Table 4.4 
Terms used to describe red blood cell characteristics

Iron deficiency anaemia

This is the most common form of anaemia in many parts of the world. The normal daily requirement of iron intake in men is about 1 to 2 mg, mainly from eating meat and highly coloured vegetables. The normal daily requirement in women is 3 mg because of blood loss during menstruation and to meet the needs of the growing fetus during pregnancy. Children, during their period of rapid growth, require more than adults.

The amount of haemoglobin in each cell is regarded as below normal when the MCH is less than 27 pg/cell (
Table 4.1
). The anaemia is regarded as severe when the haemoglobin level is below 9 g/dl blood. It is caused by deficiency of iron in the bone marrow and may be due to dietary deficiency, excessively high requirements or malabsorption.

In this type of anaemia erythrocytes are microcytic and hypochromic because their haemoglobin content is low.

Iron deficiency anaemia can result from deficient intake, unusually high iron requirements, or poor absorption from the alimentary tract.

Deficient intake

Because of the relative inefficiency of iron absorption, deficiency occurs frequently, even in individuals whose requirements are normal. The risk of deficiency increases if the daily diet is restricted in some way, as in poorly planned vegetarian diets, or in weight-reducing diets where the range of foods eaten is small. Babies dependent on milk may also suffer mild iron deficiency anaemia if weaning on to a mixed diet is delayed much past the first year, since the liver carries only a few months’ store and milk is a poor source of iron.

High requirements

In pregnancy iron requirements are increased both for fetal growth and to support the additional load on the mother’s cardiovascular system. Iron requirements also rise when there is chronic blood loss, the causes of which include peptic ulcers (
p. 315
), heavy menstrual bleeding (menorrhagia), haemorrhoids or carcinoma of the GI tract (
pp. 316
,
320
).

Malabsorption

Iron absorption is usually increased following haemorrhage, but may be reduced in abnormalities of the stomach, duodenum or jejunum. Because iron absorption is dependent on an acid environment in the stomach, an increase in gastric pH may reduce it; this may follow removal of part of the stomach, or in pernicious anaemia (see below), where the acid-releasing (parietal) cells of the stomach are destroyed. Loss of surface area for absorption in the intestine, e.g. after surgical removal, can also cause deficiency.

Megaloblastic anaemias

Deficiency of vitamin B
₁₂
and/or folic acid impairs erythrocyte maturation (
Fig. 4.4
) and abnormally large erythrocytes (
megaloblasts
) are found in the blood. During normal erythropoiesis (
Fig. 4.2
) several cell divisions occur and the daughter cells at each stage are smaller than the parent cell because there is not much time for cell enlargement between divisions. When deficiency of vitamin B
₁₂
and/or folic acid occurs, the rate of DNA and RNA synthesis is reduced, delaying cell division. The cells can therefore grow larger than normal between divisions. Circulating cells are immature, larger than normal and some are nucleated (MCV > 94 fl). The haemoglobin content of each cell is normal or raised. The cells are fragile and their life span is reduced to between 40 and 50 days. Depressed production and early lysis cause anaemia.

Vitamin B
₁₂
deficiency anaemia

Pernicious anaemia

This is the most common form of vitamin B
₁₂
deficiency anaemia. It is commonest in females usually between 45 and 65 years of age. It is an autoimmune disease in which autoantibodies destroy intrinsic factor (IF) and parietal cells in the stomach (
p. 292
).

Dietary deficiency of vitamin B
₁₂

This is rare, except in true vegans, i.e. when no animal products are included in the diet. The store of vitamin B
₁₂
is such that deficiency takes several years to appear.

Other causes of vitamin B
₁₂
deficiency

These include the following.

•
Gastrectomy
(removal of all or part or the stomach) – this leaves fewer cells available to produce IF.

•
Chronic gastritis, malignant disease and ionising radiation
– these damage the gastric mucosa including the parietal cells that produce IF.

•
Malabsorption
– if the terminal ileum is removed or inflamed, e.g. in Crohn’s disease, the vitamin cannot be absorbed.

Complications of vitamin B
₁₂
deficiency anaemia

These may appear before the signs of anaemia. Because vitamin B
₁₂
is used in myelin production, deficiency leads to irreversible neurological damage, commonly in the spinal cord (
p. 180
). Mucosal abnormalities, such as glossitis (inflammation of the tongue) are also common, although they are reversible.

Folic acid deficiency anaemia

Deficiency of folic acid causes a form of megaloblastic anaemia identical to that seen in vitamin B
₁₂
deficiency, but not associated with neurological damage. It may be due to:

•
dietary deficiency, e.g. in infants if there is delay in establishing a mixed diet, in alcoholism, in anorexia and in pregnancy

•
malabsorption from the jejunum caused by, e.g., coeliac disease, tropical sprue or anticonvulsant drugs

•
interference with folate metabolism by, e.g., cytotoxic and anticonvulsant drugs.

Aplastic anaemia

Aplastic (hypoplastic) anaemia results from bone marrow failure. Erythrocyte numbers are reduced. Since the bone marrow also produces leukocytes and platelets,
leukopenia
(low white cell count) and
thrombocytopenia
(low platelet count) are likely to accompany diminished red cell numbers. When all three cell types are low, the condition is called
pancytopenia
, and is accompanied by anaemia, diminished immunity and a tendency to bleed. The condition is often idiopathic, but the known causes include:

•
drugs, e.g. cytotoxic drugs, some anti-inflammatory and anticonvulsant drugs, some sulphonamides and antibiotics

•
ionising radiation

•
some chemicals, e.g. benzene and its derivatives

•
viral disease, including hepatitis.

Haemolytic anaemias

These occur when circulating red cells are destroyed or are removed prematurely from the blood because the cells are abnormal or the spleen is overactive.

Congenital haemolytic anaemias

In these diseases, genetic abnormality leads to the synthesis of abnormal haemoglobin and increased red cell membrane fragility, reducing their oxygen-carrying capacity and life span. The most common forms are sickle cell anaemia and thalassaemia.

Sickle cell anaemia

The abnormal haemoglobin molecules become misshapen when deoxygenated, making the erythrocytes sickle shaped. If the cells contain a high proportion of abnormal Hb, sickling is permanent. The life span of cells is reduced by early haemolysis, which causes anaemia. Sickle cells do not move smoothly through the small blood vessels. This tends to increase the viscosity of the blood, reducing the rate of blood flow and leading to intravascular clotting, ischaemia and infarction.

Blacks are more affected than other races. Some affected individuals have a degree of immunity to malaria because the life span of the sickled cells is less than the time needed for the malaria parasite to mature inside the cells.

Complications

Pregnancy, infection and dehydration predispose to the development of ‘sickle crises’ due to intravascular clotting and ischaemia, causing severe pain in long bones, chest or the abdomen. Excessive haemolysis results in high levels of circulating bilirubin. This in turn frequently leads to gallstones (
cholelithiasis
) and inflammation of the gall bladder (
cholecystitis
) (
p. 326
).

Thalassaemia

There is reduced globin synthesis with resultant reduced haemoglobin production and increased fragility of the cell membrane, leading to early haemolysis. Severe cases may cause death in infants or young children. This inherited condition is most common in Mediterranean countries.

Haemolytic disease of the newborn

In this disorder, the mother’s immune system makes antibodies to the baby’s red blood cells, causing destruction of fetal erythrocytes. The antigen system involved is usually (but not always) the Rhesus (Rh) antigen.

A Rh
⁻
mother carries no Rh antigen on her red blood cells, but she has the capacity to produce anti-Rh antibodies. If she conceives a child fathered by a Rh
⁺
man, and the baby inherits the Rh antigen from him, the baby may also be Rh
⁺
, i.e. different from the mother. During pregnancy, the placenta protects the baby from the mother’s immune system, but at delivery a few fetal red blood cells may enter the maternal circulation. Because they carry an antigen (the Rh antigen) foreign to the mother, her immune system will be stimulated to produce neutralising antibodies to it. The red cells of second and subsequent Rh
⁺
babies are attacked by these maternal antibodies, which can cross the placenta and enter the fetal circulation (
Fig. 4.14
). In the most severe cases, the baby dies in the womb from profound anaemia. In less serious circumstances, the baby is born with some degree of anaemia, which is corrected with blood transfusions.