The Blood

3.4a The physiology of the blood

When hemoglobin attracts and holds on to oxygen molecules, it turns bright red, giving the blood its characteristic color. When it releases oxygen, the color of the hemoglobin, 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.

Hemoglobin 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 anemia and acute blood loss (see Sections 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 hemoglobin and recycled for further use in the body. The by-product of this process is bilirubin, which is a digested form of hemoglobin, and this is taken up by the liver and excreted into the bile (see Section 3.1a).

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

The ABO system categorizes blood type according to the presence or absence of two genetically determined polysaccharides (antigens) known simply as A and B that are present 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, categorizes 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 Section 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 Chapters 2.1 and 2.2.

The role of the blood

The blood is 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, warm temperature, and the perfect balance of acidity and salts, and is also 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.

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.

Full blood count

The full blood count (FBC) is one of the most commonly performed blood tests. The FBC can give information about all three types of blood cell (red blood cells, white blood cells or leukocytes and platelets).

To perform an FBC, about 5 milliliters of venous blood is taken by syringe, usually from a vein at the elbow (in the approximate area of acupoint Chi Ze, LU-5). This blood is mixed in a tube with an anticoagulant to prevent clotting, and sent to a laboratory where it is examined by means of a cell counter machine. This is able to recognize the various blood cells in the sample by their size, and gives a figure for the numbers of the different sorts of blood cell within the sample. The relative numbers of the different sorts of leukocytes, the concentration of hemoglobin in the sample and the sizes of the red blood cells can also be measured.

These figures are then compared to the normal range of values found in an average population. The FBC can show if there are too many or too few of any one type of blood cell, if the hemoglobin is too low, and if the red cells are abnormal in shape or size.

Blood film

In this examination of the blood, a drop of the blood sample taken for the FBC is placed on a microscope slide and examined by a hematologist. This examination can give more precise information about abnormalities in the shape and structure of the various blood cells.

Erythrocyte sedimentation rate (ESR)

The erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP) are both measures of an active inflammatory response taking place in the body. The ESR is simply a measure of how rapidly the red blood cells settle out of a shaken sample of blood, like particles of mud might settle out of a sample of river water. The rate at which the cells settle is dependent on the proteins such as antibodies in the plasma. The ESR is raised if the body is dealing with an ongoing infection, inflammation, cancer or trauma. The ESR is not very specific, but if raised, is a sign that there is an ongoing state of physical imbalance in the body.

C-reactive protein (CRP)

CRP is one of the plasma proteins, the levels of which rise during inflammation. If the CRP level is raised, the body is dealing with acute inflammation or trauma. This test is therefore a bit more specific than the ESR, but is more expensive to perform.

Serum samples

Serum can be obtained from the blood by allowing venous blood to clot in a test tube. The fluid that separates from the clot is plasma without the clotting factor fibrinogen. This fluid is called serum. A wide range of assays can be performed on the serum sample to investigate diseases that affect the body systems. For example, substances as diverse as vitamin C, insulin, calcium and cannabis are all detected from serum samples, although a separate blood sample is required for each assay.

Contrary to what many patients might expect, a single blood test cannot reveal information about all these diseases and substances. A single sample of about 7 milliliters of blood can only be used for one or two assays. Alcohol, for example, will only be detected if the alcohol assay has been requested. Even if present, alcohol will not be detected if the doctor has requested that the blood is tested only for thyroid hormone.

In the investigation of the diseases of the blood, some of the most commonly performed serum tests are for iron, vitamin B12 and folic acid (also called folate in some texts), all of which are important in the investigation of anemia.

Examination of the bone marrow

In all severe conditions of the blood, including anemia, 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 anesthetic. Despite the anesthetic 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 visualize the lymph nodes

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

3.4c Anemia

Anemia is a term derived from the Greek 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 anemia, the concentration of hemoglobin in the blood is less than that in healthy people.

In Section 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 anemia. In acute blood loss, the red cells and concentration of hemoglobin are normal, but the volume of the circulating blood is reduced.

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

Despite the variety of causes of the condition, there are some features that all patients with anemia have in common.

The clinical features of anemia

Symptoms of tiredness, breathlessness and feeling faint, together with the sign of pallor, are characteristic of anemia. In addition, palpitations, chest pain and edema may also be experienced by the patient with severe anemia. There is also a range of other symptoms that are specific to particular types of anemia.

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 anemia.

The sign of pallor is due to the reduction in levels of the bright red colored hemoglobin in the blood.

The causes of anemia

The causes of anemia are conventionally categorized into two groups:

•anemia due to impaired production of red blood cells

•anemia due to increased destruction of red blood cells.

Impaired production of red blood cells

Impaired production of red blood cells most commonly results from a deficiency of the three essential factors required for the healthy development of red blood cells: iron, vitamin B12 and folic acid. This leads to an anemia in which the red blood cells produced in the bone marrow are unable to carry the amount of oxygen that could be carried by normal red blood cells.

Another important cause of reduced production of red blood cells is bone marrow failure. The most common cause of bone marrow failure is cancer. Secondary cancer and blood cancers can form in the marrow spaces in the bones and prevent the healthy growth of bone marrow.

Red blood cells are also under-produced in severe chronic disease such as kidney failure (chronic renal failure) or rheumatoid arthritis. In kidney failure the anemia results from insufficient production of erythropoietin, which is normally made by the healthy kidneys. In other chronic diseases, the cause for the anemia is less clearly understood. Anemia of chronic disease (AOCD) may be a mild anemia, but can still be sufficiently severe to lead to symptoms.

Increased destruction of red blood cells

Red blood cells can become prematurely destroyed either because they have become damaged in some way, or because there is excessive enlargement of the spleen, the main organ responsible for the natural breakdown of the red cells. Again, in these types of anemia the number of red blood cells in the blood is reduced.

The inherited conditions of sickle cell anemia and thalassemia are both conditions in which the red cells are abnormal in shape and are more prone to destruction. Both these conditions are examples of anemia due to the premature destruction of red cells.

Anemias resulting from impaired production of red blood cells

Iron-deficiency anemia

Iron-deficiency anemia is the most common cause of anemia 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 anemia 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 anemia that can result from malaria and other parasitic infections.

Iron-deficiency anemia 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 a sole source of iron in children over the age of one. 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 older 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 Section 3.1e).

In health, the body holds a lot of iron in reserve. The bulk of this is held within the hemoglobin 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 is 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 store will eventually run out, as iron is gradually lost through sweat and urine as well as through bleeding.

Pregnancy and the months following childbirth are recognized 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 recognized 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 anemia. 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 recognized 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 hemoglobin. 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 anemia will experience all the general symptoms of anemia, their severity depending on how much the level of hemoglobin has been reduced. Additional symptoms that are recognized to occur in iron-deficiency anemia 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). 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 anemia, 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 gynecologist may be made for the treatment of heavy menstrual bleeding (see Section 5.2c).

Dietary causes of anemia can be rapidly addressed by giving the patient iron supplements in tablet form. Ferrous sulfate 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) that are claimed to have fewer of these side effects.

Iron supplements are given in pregnancy very often in mild cases of anemia, to counter 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. This is considered important as anemia at the time of labor is associated with poorer outcomes and excess maternal bleeding.

It is only in very extreme cases of anemia, 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 anemia due to malabsorption or blood loss, the cause of the anemia should be treated in addition to supplementing the iron stores of the body with iron preparations.

A healthy stomach is required for the uptake of vitamin B12, because the parietal cells of the stomach lining are the source of a chemical called intrinsic factor, which is necessary for the absorption of the vitamin. People who have had their stomach removed by surgery are prone to vitamin B12 deficiency for this reason. However, the most common condition to affect the stomach and prevent healthy absorption of vitamin B12 is pernicious anemia. In pernicious anemia the parietal cells of the stomach lining are gradually damaged by an autoimmune process. This condition is most common in middle-aged and older women. It tends to run in families, and this suggests an inherited susceptibility to autoimmune disease.

Lack of vitamin B12 leads to impaired development of the red blood cells. The affected cells are larger than normal, but do not contain sufficient hemoglobin for adequate oxygen transport. The general symptoms and signs of anemia are present, although the pallor may have a slight yellowy tinge. Lack of vitamin B12 affects other tissues, and this leads to additional symptoms. As in iron-deficiency anemia, a sore mouth and tongue can develop. However, the most serious symptoms relate to the nervous system.

In advanced pernicious anemia the patient develops numbness and weakness of the limbs, impaired vision, and eventually dementia, as the nerves are deprived of this essential vitamin. Before injectable vitamin B12 supplements were available, the damage to the nervous system led to permanent disability and sometimes death. This explains why this form of anemia was described as pernicious.

The FBC shows the enlarged blood cells suggestive of vitamin B12 deficiency, but the diagnosis is usually confirmed by means of serum tests for vitamin B12. In over 90 percent of patients with pernicious anemia antibodies are found to parietal cells and intrinsic factor, and this is usually sufficient to confirm diagnosis without performing more invasive tests.

If the cause is dietary, vitamin B12 supplements in tablet form can be given. However, in pernicious anemia these cannot be absorbed by the bowel because of the lack of intrinsic factor. Nevertheless, the symptoms of pernicious anemia can be totally reversed by regular injections of vitamin B12. These injections are usually given at three-month intervals for the rest of the patient’s life.

Although in pernicious anemia the patient does not usually suffer from any gastric symptoms, the autoimmune process affecting the lining cells of the stomach is a form of inflammation. Because of this, in some patients, it can eventually lead to cancer.