Ross & Wilson Anatomy and Physiology in Health and Illness (34 page)

Chemicals

Some chemicals encountered in the general or work environment alter the DNA of the white cell precursors in the bone marrow. These include benzene and its derivatives, asbestos, cytotoxic drugs, chloramphenicol.

Genetic factors

Identical twins of leukaemia sufferers have a much higher risk than normal of developing the disease, suggesting involvement of genetic factors.

Types of leukaemia

Leukaemias are usually classified according to the type of cell involved, the maturity of the cells and the rate at which the disease develops (see
Fig. 4.2, p. 58
).

Acute leukaemias

These types usually have a sudden onset and affect the poorly differentiated and immature ‘blast’ cells (
Fig. 4.2
). They are aggressive tumours that reach a climax within a few weeks or months. The rapid progress of bone marrow invasion impairs its function and culminates in anaemia, haemorrhage and susceptibility to infection. The mucous membranes of the mouth and upper gastrointestinal tract are most commonly affected.

Leukocytosis is usually present in acute leukaemia. The bone marrow is packed with large numbers of immature and abnormal cells.

Acute myeloblastic leukaemia (AML)

involves proliferation of myeloblasts (
Fig. 4.2
), and is most common in adults between the ages of 25 and 60, risk gradually increasing with age. The disease can often be cured, or long-term remission achieved.

Acute lymphoblastic leukaemia (ALL)

is seen mainly in children, who have a better prognosis than adults, with up to 70% achieving cure. The cell responsible here is a primitive B-lymphocyte.

Chronic leukaemias

These conditions are less aggressive than the acute forms and the leukocytes are more differentiated, i.e. at the ‘cyte’ stage (
Fig. 4.2
).

Leukocytosis is a feature of chronic leukaemia, with crowding of the bone marrow with immature and abnormal leukocytes, although this varies depending upon the form of the disease.

Chronic myeloid leukaemia (CML)

occurs at all ages and, although its onset is gradual, in most patients it eventually transforms into a rapidly progressive stage similar to AML (sometimes ALL) and proves fatal. Death usually occurs within 5 years.

Chronic lymphocytic leukaemia (CLL)

involves proliferation of B-lymphocytes, and is usually less aggressive than CML. It is most often seen in the elderly; disease progression is usually slow, and survival times can be as long as 25 years.

Haemorrhagic diseases

Learning outcomes

After studying this section, you should be able to:

indicate the main causes and effects of thrombocytopenia

outline how vitamin K deficiency relates to clotting disorders

explain the term disseminated intravascular coagulation, including its principal causes

describe the physiological deficiencies present in the haemophilias.

Thrombocytopenia

This is defined as a blood platelet count below 150 × 10
⁹
/l (150 000/mm
³
) but spontaneous capillary bleeding does not usually occur unless the count falls below 30 × 10
⁹
/l (30 000/mm
³
). It may be due to a reduced rate of platelet production or increased rate of destruction.

Reduced platelet production

This is usually due to bone marrow deficiencies, and therefore production of erythrocytes and leukocytes is also reduced, giving rise to pancytopenia. It is often due to:

•
platelets being crowded out of the bone marrow in bone marrow diseases, e.g. leukaemias, pernicious anaemia, malignant tumours

•
ionising radiation, e.g. X-rays or radioactive isotopes, which damage the rapidly dividing precursor cells in the bone marrow

•
drugs that can damage bone marrow, e.g. cytotoxic drugs, chloramphenicol, chlorpromazine, sulphonamides.

Increased platelet destruction

A reduced platelet count occurs when production of new platelets does not keep pace with destruction of damaged and worn out ones. This occurs in disseminated intravascular coagulation (see below) and autoimmune thrombocytopenic purpura.

Autoimmune thrombocytopenic purpura

This condition, which usually affects children and young adults, may be triggered by a viral infection such as measles. Antiplatelet antibodies are formed that coat platelets, leading to platelet destruction and their removal from the circulation. A significant feature of this disease is the presence of purpura, which are haemorrhages into the skin ranging in size from pinpoints to large blotches. The severity of the disease varies from mild bleeding into the skin to severe haemorrhage. When the platelet count is very low there may be severe bruising, haematuria, gastrointestinal or intracranial haemorrhages.

Vitamin K deficiency

Vitamin K is required by the liver for the synthesis of many clotting factors and therefore deficiency predisposes to abnormal clotting (
p. 64
).

Haemorrhagic disease of the newborn

Spontaneous haemorrhage from the umbilical cord and intestinal mucosa occurs in babies when the stored vitamin K obtained from the mother before birth has been used up and the intestinal bacteria needed for its synthesis in the infant’s bowel are not yet established. This is most likely to occur when the baby is premature.

Deficiency in adults

Vitamin K is fat soluble and bile salts are required in the colon for its absorption. Deficiency may occur when there is liver disease, prolonged obstruction to the biliary tract or in any other disease where fat absorption is impaired, e.g. coeliac disease. Dietary deficiency is rare because a sufficient supply of vitamin K is usually synthesised in the intestine by bacterial action. However, it may occur during treatment with drugs that sterilise the bowel.

Disseminated intravascular coagulation (DIC)

In DIC, the coagulation system is activated within blood vessels, leading to formation of intravascular clots and deposition of fibrin in the tissues. Because of this consumption of clotting factors and platelets, there is a consequent tendency to haemorrhage. DIC is a common complication of a number of other disorders, including:

•
severe shock, especially when due to microbial infection

•
septicaemia, when endotoxins are released by Gram-negative bacteria

•
severe trauma

•
premature separation of placenta when amniotic fluid enters maternal blood

•
acute pancreatitis when digestive enzymes are released into the blood

•
malignant tumours with widely dispersed metastases.

Congenital disorders

The haemophilias

The haemophilias are a group of inherited clotting disorders, carried by genes present on the X-chromosome (i.e. inheritance is sex linked,
p. 434
). The faulty genes code for abnormal clotting factors (Factor VIII and Christmas factor), and if inherited by a male child always leads to expression of the disease. Women inheriting one copy are carriers, but, provided their second X chromosome bears a copy of the normal gene, their blood clotting is normal. It is possible, but unusual, for a woman to inherit two copies of the abnormal gene and have haemophilia.

Those who have haemophilia experience repeated episodes of severe and prolonged bleeding at any site, with little evidence of trauma. Recurrent bleeding into joints is common, causing severe pain and, in the long term, cartilage is damaged. The disease ranges in severity from mild forms, where the defective factor has partial activity, to extreme forms where bleeding can take days or weeks to control.