Introduction

In this last section of Stage 3 the physiology and pathology of the blood and its associated diseases are explored. Some of the different aspects of the function of the blood have already been described when discussing inflammation, clotting, the immune system and the cardiovascular system.

The composition of the blood

In Chapter 2.1c it was explained that the blood is composed of a fluid called plasma and three types of blood cells: the red blood cells (erythrocytes), the white blood cells (leukocytes) and the platelets (thrombocytes).

The blood cells

All three types of blood cell originate from the bone marrow. The bone marrow contains a number of immature cells called ‘stem cells’, and it is these that are the starting material for all the different subtypes of blood cells, including all the leukocytes, such as macrophages and mast cells, which leave the blood to perform immune functions in the tissues. Figure 3.4a-I gives a diagrammatic representation of how the stem cell is the ‘great grandparent’ of the red blood cell (the erythrocyte), the platelet and the six different categories of white blood cell (the granulocytes and agranulocytes). It is important to appreciate this process before approaching the study of the condition of leukaemia.

Figure 3.4a-I • The stages in the development of the blood cells.

Red blood cells (erythrocytes)

The primary function of red blood cells is to carry oxygen from the lungs to the tissues. To do this, red blood cells contain an iron-containing protein called ‘haemoglobin’, which has a strong affinity for oxygen molecules. Because of its haemoglobin, a red blood cell can carry much more oxygen than could be dissolved in an equivalent volume of plasma, and this is essential to enable the blood to carry sufficient oxygen for the body’s requirements.

When haemoglobin attracts and holds on to oxygen molecules, it turns bright red, giving the blood its characteristic colour. When it releases oxygen, the colour of the haemoglobin, and therefore the blood, becomes a more purple shade of red. This is why arterial blood in the body circulation is bright red and venous blood is darker.

The haemoglobin is manufactured within the maturing red blood cell in the bone marrow. Iron, obtained from the diet, is an essential ingredient in this process. The vitamins folic acid and vitamin B₁₂, also obtained from the diet, are important factors that enable the production of healthy red blood cells.

The production of red blood cells is stimulated by the hormone erythropoietin, which is released by the kidneys. The hormone is released when the blood fails to perform its role of oxygenation of tissues in the conditions of anaemia and acute blood loss (see Chapters 3.4c and 3.4d).

Before the maturing red blood cell leaves the bone marrow to enter the blood, the nucleus breaks down. The red blood cell then takes on a disc-like shape, which enables it to be flexible enough to move in large numbers through the finest capillaries. Once in the circulation, the life of the red blood cell is about 120 days, after which it is broken down in the spleen, the liver, and parts of the bone marrow by phagocytic white blood cells. In this process, the iron is removed from the haemoglobin and recycled for further use in the body. The by-product of this process is bilirubin, which is a digested form of haemoglobin, and this is taken up by the liver and excreted into the bile (see Chapter 3.1a) (see Q3.4a-3).

The surface of the red blood cells expresses characteristic forms of polysaccharide molecules, and these are the basis for categorising a person into one of the four blood groups, A, B, AB or O, and also as whether they are rhesus (Rh) positive or rhesus negative. This terminology reflects the two important ways in which blood groups are classified: the ABO system and the rhesus system.

The ABO system categorises blood according to the presence or absence of two genetically determined polysaccharides (antigens), known simply as A and B, on the surface of the red blood cell. Group A means that substance A is carried on all the red cells, whereas the red cells of group B carry substance B. The red cells of blood group AB carry both A and B, whereas those of blood group O carry neither.

The rhesus system, at its most simple, categorises blood into whether or not it carries a particular substance called rhesus D. Rhesus-positive people carry rhesus D on their red cells. The rhesus system is independent of the ABO system.

If blood of different blood groups is mixed there is a tendency for the red blood cells to clump together and break down. This is called ‘incompatibility’, and results from antibodies to ‘foreign’ blood groups present in the serum of the blood samples. Some combinations of blood groups are much more likely to have this reaction than others. For this reason, before being used in a blood transfusion, donated blood is ‘typed’ to ensure that the ABO and rhesus D factors are exactly the same as those of the intended recipient.

Platelets (thrombocytes)

The platelets, like the red blood cells, are cells without nuclei that originate from the bone marrow. Their function is to work together with the clotting-factor proteins in the plasma to enable an efficient and controlled clotting reaction (see Chapter 2.1c).

White blood cells (leukocytes)

The diverse functions of the white blood cells were introduced in the description of wound healing, inflammation and the immune system in Sections 2.1 and 2.2.

There are two broad groups of white blood cell, which are categorised according to whether or not the cytoplasm contains granules. These are the granulocytes and agranulocytes (see Figure 3.4a-I).

Granulocytes contain granules, which consist of chemicals (enzymes) that are important for the destruction of unwanted foreign matter and in the generation of inflammation. Some of the granulocytes are able to phagocytose (see Chapter 1.1c) small particles such as damaged bacteria. All the granulocytes can move, like an amoeba, out of the blood vessels and into the tissues when their presence is required.

The agranulocytes, which include the lymphocytes and monocytes, do not contain granules. Lymphocytes are the cells that provide the foundation of the immune response. They secrete antibodies in response to antigens and carry specific antibodies on their surface. Monocytes are cells that are able to phagocytose foreign material and debris from damaged and ageing cells. Macrophages are a type of monocyte that are plentiful in connective tissue for this purpose.

The role of the blood

The blood is a part of the body that is in constant movement, and which by means of the blood vessels reaches all body parts. Its primary role is to transport essential substances from one part of the body to another and to remove waste products.

It is because of the healthy flow of blood that all the cells of the body can have a constant environment. This environment provides water, nutrients, oxygen, protection, the perfect balance of acidity and salts, and warm temperature, and is always cleansed of wastes. In short, blood is a cornerstone of the state of balance called ‘homeostasis’, and the fact that it is crucial for maintaining balance is of course likely to be of interest to those who hold to a holistic approach to medicine (see Q3.4a-4-Q3.4a-5).

Introduction

Mild forms of the most common non-cancerous diseases of the blood, the anaemias, may be investigated and managed solely by a family physician (GP), who is able to examine the patient and take blood samples to be sent to a laboratory for interpretation.

The investigation of more severe diseases of the blood is carried out by a hospital specialist called a ‘haematologist’. A doctor who specialises in haematology has been trained not only in the clinical skills required to examine and treat patients with blood diseases, but also in the examination of samples of blood and bone marrow under the microscope.

The investigation of the diseases of the blood involves:

Physical examination

The physical examination of a patient with a suspected disease of the blood involves the stages listed in Table 3.4b-I.

Table 3.4b-I The stages of physical examination of the blood

Blood tests

A great deal of information can be obtained about the blood from tests that involve the patient in relatively little discomfort. All the tests described below are used in the investigation of a wide range of diseases affecting all the body systems. Because these tests are performed so frequently, they are described in some detail.

Examination of the bone marrow

In all severe conditions of the blood, including anaemia, examination of the bone marrow can reveal whether there are abnormalities in the development of the blood. The blood-forming marrow is a dense blood-like fluid that can be drawn up into a syringe. The removal of the sample of bone marrow involves the insertion of a large needle into the bone of the iliac crest after the area has been numbed with a local anaesthetic. Despite the anaesthetic this is a much more painful procedure than the simple blood test.

The sample obtained is examined in the same way as the blood film. The bone marrow sample will reveal the shape and structure of the stem cells and the immature forms of the three different types of blood cell.

Biopsy and other tests to visualise the lymph nodes

The two most common forms of cancer that affect the cells of the blood are leukaemia and lymphoma. These diseases are the focus of Chapter 3.4e. In both these conditions the lymph nodes may become engorged with increased numbers of cancerous white blood cells.

In lymphoma, the lymph node is the primary site of the tumour. Surgical removal and examination (biopsy) of an affected superficial node can give valuable information about the tumour. Computed tomography (CT) scans can give more information about the state of lymph nodes deeper in the body. Both these tests can be important for the accurate staging of lymphomas.

Introduction

‘Anaemia’ is a term derived from the Greek words meaning ‘no blood’, and is used to describe the range of conditions that lead to an impairment in the ability of the red blood cells to transport oxygen to the tissues. In a person with anaemia, the concentration of haemoglobin in the blood is less than that in healthy people.

In Chapter 3.4d the ways in which a sudden loss of a large quantity of blood might affect the body are explored. Although this condition also reduces the ability of the blood to transport oxygen to the tissues, this is not the same as anaemia. In acute blood loss, the red cells and the concentration of haemoglobin are normal, but the volume of the circulating blood is reduced.

It is important at this stage to clarify that the term ‘anaemia’ does not say anything about the underlying disease process. It simply describes the end result. If doctors are to treat anaemia effectively, the underlying cause of the problem must first be diagnosed.

However, despite the variety of causes of the condition, there are some features that all patients with anaemia have in common.

The clinical features of anaemia

Symptoms of tiredness, breathlessness and feeling faint, together with the sign of pallor are characteristic of anaemia. In addition, palpitations, chest pain and oedema may also be experienced by the patient with severe anaemia. There are also a range of other symptoms that are specific to particular types of anaemia (see Q3.4c-1).

The symptoms of tiredness, breathlessness and depression are a consequence of the cells of the body not receiving the nourishment, in the form of oxygen, that they require. Oxygen is an essential ingredient in the process of cell respiration, and thus it is understandable how an insufficient supply of oxygen to the tissues of the body can lead to these general symptoms of anaemia (see Q3.4c-2).

The sign of pallor is due to the reduction in levels of the bright red coloured haemoglobin in the blood.

Palpitations and chest pain occur in severe anaemia because the heart responds to the reduced level of oxygen in the blood by pumping faster. This has the initially beneficial effect of increasing the amount of oxygen that reaches the tissues at any one time, but can place strain on the heart muscle itself. The symptoms of angina may result in someone who has a degree of atherosclerosis, and occasionally oedema may develop as a result of heart failure.

The causes of anaemia

The causes of anaemia are conventionally categorised into two groups:

The anaemias resulting from impaired production of red blood cells

Iron-deficiency anaemia

Iron-deficiency anaemia is the most common cause of anaemia in western countries. Moreover, it is one of the most important causes of ill-health worldwide. In developing countries, deficiency of iron in the diet contributes to poor growth and development, and impairs the ability to fight infections. Iron-deficiency anaemia is the underlying cause of millions of premature deaths, especially of women in childbirth, babies and children. Iron deficiency can be compounded in people in tropical countries by the anaemia that can result from malaria and other parasitic infections.

Iron-deficiency anaemia can result either from inadequate amounts of iron-containing foods in the diet, or from excessive loss of the iron contained in the blood. A combination of the two is commonly present.

Iron is initially obtained in infancy from breast milk, although the amount of iron in breast milk is considered to be insufficient as the only source of iron in children over the age of 1 year. For this reason, many milk formulas produced for bottle feeding are supplemented with iron. After weaning, iron is obtained from foods such as meat and fish, eggs, whole grains and dark leafy vegetables. In the west many processed cereal products are fortified with iron.

In the west, despite an abundance of food, many people are at risk of iron deficiency because of an inadequate diet. People who are particularly at risk are small children, people on long-term slimming diets, vegetarians and vegans, and elderly people.

Another group of people who are at risk of iron deficiency are those who cannot absorb iron from the diet because of malabsorption (see Chapter 3.1e).

In health, the body holds a lot of iron in reserve. The bulk of this is held within the haemoglobin of the red cells, and is ‘recycled’ for further use when the old red cells are broken down by the spleen. The remainder of the body’s iron stores are found in the liver and the muscles. The body can withstand a period of weeks of a relatively low intake of dietary iron. However, unless the diet can provide sufficient iron, the stores will eventually run out, as iron is gradually lost through the sweat and urine as well as through bleeding.

Iron stores run out much more quickly if excessive blood is lost on a recurrent basis. As many blood donors might wish to testify, the body can withstand a significant loss of blood as long as sufficient time is allowed for the iron stores to recover before the next episode of blood loss. However, in some situations a steady loss of iron from long-term bleeding may be too great to be recovered from the diet alone. This most commonly results from heavy menstrual bleeding, or in people who are unknowingly losing just a few millilitres of blood a day into their bowel from gastrointestinal conditions such as a stomach ulcer. In these cases, the iron stores gradually run down until the manufacture of red cells is affected, and then anaemia develops.

Pregnancy and the months following childbirth are recognised as times during which the iron stores can become depleted. The pregnant woman loses iron as it passes through the placenta to the developing fetus, and then a large amount of blood can be lost at delivery. The iron stores will be depleted further as the mother breastfeeds.

It is recognised that it is very common for iron stores to be depleted, although not by enough to affect the production of red blood cells and to cause anaemia. This is called ‘latent iron deficiency’, and is obviously a state in which the body is not in a good state of balance. Latent iron deficiency is not conventionally recognised to be associated with specific symptoms.

When the iron stores are very low, the red cells produced in the bone marrow are small and pale because of the reduced amount of haemoglobin. They are also reduced in number. This pattern is characteristic of iron deficiency, and so a simple FBC can often be all that is needed to confirm the diagnosis. Serum samples will show reduced levels of iron in the blood.

A patient with iron-deficiency anaemia will experience all the general symptoms of anaemia, their severity depending on how much the level of haemoglobin has been reduced. Additional symptoms that are recognised to occur in iron-deficiency anaemia are believed to be a result of deficiency of iron in certain other tissues of the body such as the skin, the mucous membranes and the nails. In severe iron deficiency a patient might have dry skin and a tendency to bruising, concave (spoon-shaped) nails and a sore tongue and cracked lips. The tongue loses its coat and can appear bright red (likened to a beefsteak). It is known that, in very severe cases, the retina at the back of the eye can show areas of swelling and bleeding, and this carries a risk of blindness.

In all cases of iron-deficiency anaemia, the diagnosis alone is not a sufficient basis on which to start treatment. In all cases, the possibility of malabsorption or excessive blood loss should also be excluded, and this may involve the patient in a referral to a gastroenterologist to exclude chronic bowel disease or bleeding from the bowel. A referral to a gynaecologist may be made for the treatment of heavy menstrual bleeding (see Chapter 5.2c).

Dietary causes of anaemia can be rapidly addressed by giving the patient iron supplements in tablet form. Ferrous sulphate and ferrous fumarate are two common preparations. Many iron supplements cause gastrointestinal side-effects such as nausea, acid indigestion and constipation, although more naturally derived preparations are available (not on prescription) which are claimed to have fewer of these side-effects.

Iron supplements are given in pregnancy often in mild cases of anaemia, because of the anticipated further iron losses that might occur during childbirth and breastfeeding. Unfortunately, the side-effects of nausea, indigestion and constipation can be particularly problematic in pregnancy.

It is only in very extreme cases of anaemia, or in cases in which the bowel cannot absorb iron, that iron is given by other means. In these cases iron may be given by intravenous injection, although this carries risks of more severe side-effects.

In anaemia due to malabsorption or blood loss, the cause of the anaemia should be treated in addition to supplementing the iron stores of the body with iron preparations.

Information Box 3.4c-II Iron-deficiency anaemia: comments from a Chinese medicine perspective

In Chinese medicine, the symptoms of iron-deficiency anaemia closely correspond to the syndromes of Heart and Liver Blood (and Yin) Deficiency with Qi Deficiency.

Iron-containing foods include meat and fish, eggs, whole grains and dark leafy vegetables. All these foods would be considered in Chinese medicine to be ‘Blood Forming’.

Latent iron deficiency is not conventionally recognised to lead to any symptoms. However, it is possible that those non-anaemic people who experience the symptoms of Blood Deficiency might have latent iron deficiency. This might explain why it is recognised in Chinese medicine that a diet rich in ‘Blood Forming’ foods can be of benefit to all people with Blood Deficiency, even if they are not anaemic. The ‘Blood Forming’ diet will build up the iron stores of people with latent iron deficiency, and so will help these people regain a more balanced energetic state.

Medicinal iron preparations nourish the Blood but are also Heating in nature and can deplete Stomach Yin. They may also Stagnate Liver Qi.

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