Haematology Nursing E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
Haematology Nursing is a comprehensive handbook, with a nursing focus, on the care and management of patients with haematological disorders. Divided into four sections, the first provides an introduction to haematology, looking at haemopoiesis, immunology and genetics. Section Two covers non-malignant haematology, including anaemia, haemoglobinopathies and haemochromatosis. Section Three explores the pathophysiology, care and management of myeloproliferative and lymphoproliferative disorders, including leukaemia, myeloma, and lymphoma. The final section provides information on various nursing care interventions, including blood transfusion, venous access devices, and palliative care.
Aimed principally at nurses working in a variety of settings including haematology/oncology wards, medical/haematology wards, specialist bone marrow transplant centres, and community settings, Haematology Nursing is an essential and much-needed reference guide.
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Seitenzahl: 615
Veröffentlichungsjahr: 2012
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Contents
Contributors
Foreword
Section 1 Introduction to haematology
Chapter 1 Understanding haemopoiesis
Introduction
Myeloid lineage bone marrow cells
Lymphoid lineage marrow cells
T-lymphocytes
B-lymphocytes
Monocytes
Conclusion
Chapter 2 Immunology
What does the immune system do?
Friendly bacteria
Innate immunity
Inflammation
Acquired (specific) immunity
The immune response
Conclusion
Chapter 3 Genes and haematology
Overview of chromosomes, genes and DNA
From DNA to protein
Gene mutations
Point mutations
Haemoglobin and the haemoglobinopathies
Hereditary (primary) haemochromatosis
Chromosomal abnormalities
Inheritance patterns
Clinical application
Conclusion
Websites of interest
Chapter 4 The cell*
What is a cell?
How does the cell develop and replicate?
How is the cell cycle controlled?
Apoptosis
Different types of cells
What happens when the cell undergoes malignant changes?
Haematological malignancies
Section 2 Non-malignant haematology
Chapter 5 Aplastic anaemia: pathophysiology, care and management
Introduction
The bone marrow
Bone marrow failure
Incidence and pathophysiology
Presentation
Diagnosis
Management
Treatment
Supportive care
Chapter 6 Nutritional anaemia: pathophysiology, care and management
Introduction
Aetiology and epidemiology
Classifying anaemia
Signs and symptoms of anaemia
Investigations
Nutritional anaemia
Iron deficiency anaemia
Vitamin B12 (cobalamin) deficiency
Symptoms of pernicious anaemia
Folic acid deficiency
Nursing and management for patients with pernicious anaemia and folate deficiency
Conclusion
Chapter 7 Acquired haemolytic anaemia: pathophysiology, care and management
Introduction
Immune haemolytic anaemia
Autoimmune haemolytic anaemia
Warm autoimmune haemolytic anaemia
Cold autoimmune haemolytic anaemia
Paroxysmal cold haemoglobinuria
Drug induced haemolysis
Drug induced immune haemolytic anaemia
Paroxysmal nocturnal haemoglobinuria
Key principles of nursing for a patient with acquired haemolytic anaemia
Conclusion
Chapter 8 Inherited haemolytic anaemia: pathophysiology, care and management
Introduction
Hereditary spherocytosis
Glucose-6-phosphate dehydrogenase deficiency
Conclusion
Chapter 9 Sickle cell disease and thalassaemia: pathophysiology, care and management
Introduction
Sickle cell trait and thalassaemia trait
Sickle cell disease
Alpha thalassaemia
Haemoglobin H disease
Alpha thalassaemia major
Beta thalassaemia
Nursing care of patients with sickle cell disease and thalassaemia
Conclusion
Chapter 10 Haemochromatosis: pathophysiology, care and management
Introduction
Genetic information
Who does it affect?
Clinical symptoms
Diagnostic testing
Treatment for haemochromatosis
Blood donation for people with haemochromatosis
Nursing care for venesection
Screening and counselling
Training for practitioners and educational requirements
Accountability
Conclusion
Section 3 Myeloproliferative and lymphoproliferative disorders
Chapter 11 Polycythaemia: pathophysiology, care and management
Introduction
Absolute polycythaemia
Secondary polycythaemia
Apparent polycythaemia
Investigations and diagnosis
Signs and symptoms
Nursing care and management
Conclusion
Chapter 12 The myelodysplastic syndromes: pathophysiology, care and management
Introduction
Myelodysplastic syndromes: the diseases
Diagnosis
Classification of myelodysplastic syndrome
Treatment and management of myelodysplastic syndromes
Specific nursing issues
Specific education and information needs
Psychological impact
Social implications
Conclusion
Chapter 13 Acute leukaemia: pathophysiology, care and management
Introduction
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Nursing intervention and care of patients with acute leukaemia
Specific nursing intervention
Conclusion
Chapter 14 Chronic leukaemia: pathophysiology, care and management
Chronic myeloid leukaemia
Diagnosis
Presentation
Treatment
Chronic lymphocytic leukaemia
Conclusion
Chapter 15 Multiple myeloma: pathophysiology, care and management
Introduction
Pathology of multiple myeloma
Epidemiology, aetiology, genetics and incidence
Signs and symptoms
Investigations
Diagnosis
Staging of multiple myeloma
Treatment and nursing care in multiple myeloma
Treatment
Nursing care
Conclusion
Chapter 16 Lymphoma: pathophysiology, care and management
Role of the lymphocyte
Diagnostic investigations
Revised European American Lymphoma Classification adopted by the World Health Organisation
Hodgkin’s lymphoma
Histological subtypes of Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma
Conclusion
Section 4 Nursing care interventions
Chapter 17 Blood transfusion
Introduction
Blood groups
Blood components and products
Red cells
Platelets
Fresh frozen plasma
Granulocytes
Irradiated blood components
Cytomegalovirus negative blood components
Human leucocyte antigens matched platelets
Blood products and plasma derivatives
Nursing care of the patient undergoing blood transfusion therapy
Transfusion reactions
Governance, regulation and legislation
Conclusion
Chapter 18 Venous access devices
Introduction
Classification of vascular access devices
Gauge sizes
Valved and non-valved devices
Construction material
Clinical indications
Care and management
Phlebitis
Thrombosis
Pinch-off syndrome
Patient assessment
Device removal
Conclusion
Chapter 19 Chemotherapy and monoclonal antibodies
What is cytotoxic chemotherapy?
How does chemotherapy work?
Chemotherapy drug classification
Combination chemotherapy
Chemotherapy cycles
Drug dosage
Routes of administration
Health and safety
Side effects
Communication and information giving
Monoclonal antibodies
Conclusion
Chapter 20 Haemopoietic stem cell transplant
Haemopoietic stem cells
Conditioning
Types of haemopoietic stem cell transplant
Complications of haemopoietic stem cell transplant
Conclusion
Chapter 21 Palliative care in haematology
Introduction
An overview of the clinical context
Defining and delivering palliative care
Implications for practice and conclusions
Glossary of terms
Index
This edition first published 2012© 2012 by Blackwell Publishing Ltd.
Chapter 4 is adapted from Chapter 4 of The Biology of Cancer, First Edition. Janice Gabriel. © 2007 John Wiley & Sons, Ltd. Used with permission.
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Library of Congress Cataloging-in-Publication Data
Haematology nursing / [edited by] Marvelle Brown, Tracey J. Cutler.p. ; cm.Includes bibliographical references and index.
ISBN 978-1-4051-6996-7 (pbk. : alk. paper)I. Brown, Marvelle. II. Cutler, Tracey J.[DNLM: 1. Hematologic Diseases–nursing. WY 152.5]616.1′50231–dc23
2011048152
A catalogue record for this book is available from the British Library.
This book is published in the following electronic formats: ePDF 9781118276112; ePub 9781118276129; Mobi 9781118276105
Contributors
Editors
Marvelle Brown has been in the NHS and nurse education for over 30 years. In 1991, she developed the first professionally and academically recognised haematology course in England. She went on to further develop this into both a diploma and degree. She was a member of one of the working groups, which led to the development of the NICE Guidance in Haemato-oncology.
She was Chair of the RCN Haematology/BMT Forum and is currently Chair of the Acute Nurses Forum for Sickle Cell and Thalassemia.
Marvelle was a non-executive director for a north-west London hospital trust and is currently a non-executive director for Milton Keynes PCT. She became a work based fellow in 2009. Marvelle is a senior lecturer in haematology and her role expanded to lead on international nursing education.
Marvelle has written a number of articles and chapters on haematology.
She is an invited speaker nationally and internationally on a wide number of issues in haematology nursing and is completing her PhD.
Tracey Cutler began nursing in haematology in 1987, first in Bristol with children undergoing bone marrow transplant and receiving chemotherapy for haematological and oncological conditions. She then moved to Birmingham into the adult setting.
The majority of her nursing experience is in haemopoietic stem cell transplant and she progressed to a clinical nurse specialist as the transplant coordinator.
Tracey was on the working committee for the NICE (2003) Improving Outcomes in Haemato- oncology and has presented nationally and internationally.
Tracey now works as a senior lecturer in education and ran the specialist degrees in haematology, cancer care and chemotherapy for ten years. Her role has now developed to assist practitioners in their ongoing professional and academic development.
Contributors
Janice Gabriel has worked in cancer nursing for over 30 years and has had an interest in vascular access devices since the early 1980s. In 1993 she received a Nightingale Scholarship to visit the USA to independently assess the use of PICCs for patients undergoing chemotherapy. In 1994 she placed her first PICC here in the UK. Janice is currently Nurse Director for the Central South Coast Cancer Network, based in Portsmouth.
Jackie Green qualified as an RGN in 1989 and very quickly realised her passion was in cancer nursing. In 1990 she trained as an oncology nurse and went on to set up a haematology day care unit and developed the clinical haematology service. In 2001 she moved to Kings College Hospital as a lead cancer nurse and senior nurse in haematology and cancer.
In 2002 she returned to Mayday University Hospital in the role of a nurse consultant for haematology and cancer, as well as a lead cancer nurse.
Jan Green completed her nurse training in 1988 and went on to specialise in adult haematology nursing, becoming a Macmillan Haematology CNS in 1997. During her career she has set up a satellite chemotherapy unit, a venesection service for patients diagnosed with Haemochromatosis and a day case blood transfusion service for patients with Myelodysplastic Syndrome. In 2003 she became a Transfusion Liaison Nurse, supporting hospitals across the London region in the education of safe and appropriate use of blood.
Louise Knight has worked in the Translational Oncology Research Centre, Portsmouth for 10 years and gained her PhD in Modulating sensitivity and response to DNA damaging cytotoxic drugs in 2004. Her current post is Cellular Pathology Quality, Risk and Governance Manager.
Gwyneth Morgan in 1997 Gwyneth became an education and research coordinator at the West Midlands regional genetics unit and has been involved with the development of genetic programmes of study for HCPs She has since worked in higher education for a number of years, and is currently working as a senior lecturer at Birmingham City University.
Jane Richardson is a Senior Lecturer in Allied Health Sciences, she work at Worcester University in the Institute of Health and Society.
Her interests are in Genetics and Nutrition and she is a member of the British Association for Applied Nutrition and Nutrition Therapy (BANT) and the Nutrition Society.
Alison Simons has worked in oncology since qualifying almost 20 years ago. She worked within an in-patient setting looking after patients with a wide variety of cancers, undergoing chemotherapy, radiotherapy, brachytherapy, symptom management, emergency care and end of life care. She then took up the post of professional development sister responsible for oncological and haematological education and training. For the last two years she has worked at Birmingham City University as a senior lecturer in cancer care, leading the cancer care and chemotherapy programmes.
Dion Smyth has worked in cancer nursing care and education for 25 years, during which time he developed his interest and clinical service provision around the palliative, supportive and end of life care needs of patients with blood disorders. He is currently a lecturer-practitioner at Birmingham City University, UK.
Samantha Toland has worked in the field of Haematology and oncology for the last 11 years, initially working in the acute setting of a Haematology and bone marrow transplant unit, then as a specialist nurse and trainer in chemotherapy. She is currently working as a Leukaemia Nurse specialist, and also as a Senior Lecturer practitioner in Haematology at Birmingham City University.
Audrey Yandle is a Lecturer at Kings College University; she is a registered nurse with a clinical background in haematological-oncology nursing practice and has a particular interest in the nursing contribution to patient outcomes in the haematological-oncology and stem cell transplantation settings.
Foreword
Haematology is a fascinating field of clinical practice, and the developments in our understanding of haematological conditions have made this specialty a highly dynamic and exciting field in which to work. As such, it has been an area that has generated a great interest for nurses and there are now career progression opportunities to become a specialist nurse in both malignant and non-malignant haematology.
Haematology Nursing plugs a significant gap, being the first book published in the United Kingdom that addresses both these disciplines, thereby making it a valuable reference tool for all nurses managing patients with a haematological condition.
This groundbreaking textbook provides an understanding of pathology and then relates this to nursing practice. The layout of the book makes it easy for readers to navigate.
It is a comprehensive and key resource for nurses practising in haematology.
Professor Dame Sally C DaviesChief Medical Officer and Chief Scientific Adviser,Department of Health
Section 1
Introduction to haematology
Chapter 1
Understanding haemopoiesis
Marvelle Brown
This chapter aims to provide an overview of the haemopoiesis process and by the end of reading this chapter you should:
Have a detailed knowledge of all marrow cell development and functionBe aware of the different sites of haemopoiesisBe aware of the role of stem cells and how they functionUnderstand growth factors and how they functionIntroduction
Blood is not immediately thought of as an organ, but it is one of the largest in the body. The volume of blood in adults is approximately 4.5–5 litres and marrow cells form about 40% of this volume.
Haemopoiesis is the production of marrow cells and it is a fascinating process involving a diverse range of cytokinetic interactions, which produce cells responsible for gaseous exchange, fighting infections and haemostasis. Haemopoiesis is a complex process of proliferation, differentiation and maturation, with an intricate balance between demand and supply of marrow cells. Through ongoing research of haemopoiesis and the behaviour of stem cells, their relationship with growth factors, the microenvironment of the bone marrow and regulatory mechanisms are increasing knowledge of our haematological pathologies and informing therapeutic interventions.
Haemopoiesis is the name given to the production of marrow cells and this is further subdivided into erythropoiesis (production of red blood cells), leucopoiesis (production of white blood cells) and thrombopoiesis (production of platelets). In humans there are various haemopoietic sites, starting with the blood islands in the yolk sac, which forms the basis of marrow cell production for up to two months of gestation. Red blood cells are the first to be produced, with leucopoiesis and thrombopoiesis occurring from six weeks (Pallister 1997).
During this early period the main haemoglobin being produced is Gower 1 (ζ2ε2). The liver and spleen become the main sites for marrow cell production from about two months through to seven months’ gestation and here the haemoglobin is now foetal haemoglobin, Hb F (α2γ2). From six months’ gestation the skeletal system becomes the prime source of marrow cell production and with this change in site is also a gradual change in the haemoglobin from haemoglobin F (HbF) to haemoglobin A (HbA) (α2β2). The liver and spleen continue to produce marrow cells for at least two weeks after birth, but in much reduced quantities (Hoffbrand et al. 2004). The significance of the liver and spleen being sites of early marrow cell production is significant as they can revert (back) to producing marrow cells (known as ‘extramedullary’ haemopoiesis) when the bone marrow is unable to do so or is inefficient in production due to disease, such as haemato-oncological malignancies, sickle cell disease and thalassaemia syndromes (haemoglobinopathies).
During infancy and up to three years of age the entire skeletal system produces marrow cells. Progressively, there is replacement of marrow with yellow fatty tissue in the long bones and by the early twenties the distinct skeletal sites of the vertebrae, ribs, sternum, skull, proximal end of the humerus and femur, sacrum and pelvis become the only sites for haemopoiesis. In addition, similarly to the liver and spleen, the fatty tissue in the bone marrow can also reconvert to active haemopoiesis in times of increased demand.
The bone marrow has three types of stem cells, haemopoietic stem cells responsible for the production of marrow cells, endothelial tissues, which form the sinusoids, and, finally, mesenchymal stem cells. Mesenchymal stem cells differentiate into osteoblasts (bone tissue), chondrocytes (cartilage tissue) and myocytes (muscle tissue) (Litchtman et al. 2005). The existence of stems cells other than haemopoietic stem cells found in the bone marrow has generated great interest in researchers and scientists in their potential use in treating neurological and muscular diseases in the future.
All marrow cells start their development from haemopoietic stem cells, known as multipotent or pluripotent stem cells. The terms multipotent and pluripotent refer to the fact that these cells have the ability to become any type of marrow cell. These primitive progenitor cells are unrecognisable by their cell morphology but have been identified through immunological testing as being CD34+ cells. The identification of these progenitor cells as CD34+ involves the use of a monoclonal antibody (Guo et al. 2003; Yasui et al. 2003). The term CD means cluster of differentiation and relates to what are known as surface markers on a cell which are unique to that cell.
Stems cells constitute approximately 4% of the haemopoietic cells in the bone marrow and one stem cell can produce 106 cells after 20 divisions (Hoffbrand et al. 2004). The committed progenitor cells form approximately 3% and the maturing/mature cells approximately 95% of the haemopoietic stem cells (HSC) (Traynor 2006). Stem cells also have the capacity to self-renew, which is important as this means there is always a constant supply of stem cells to respond quickly to demand such as infection, haemorrhage and anaemia. Under normal circumstances, mature marrow cells are lost through normal activities and aging.
Once the HSC has been triggered all marrow cells are produced along two lines: myeloid and lymphoid. Erythrocytes, granulocytes, myelocytes and megakaryocytes are produced along the myeloid line, and lymphocytes and natural killer cells (NK) are produced along the lymphoid line. To start the differentiation process, the pluripotent stem cells can differentiate into either the precursor, colony-forming unit – granulocyte, erythrocytes, myelocytes, megakaryocytes (CFU-GEMM), or lymphoid stem cell. Differentiation of these lines produces committed cell lines. The exception is the progenitor cell, CFU-GM, which gives rise to monocytes and neutrophils. As a cell goes through its stages of development, it progressively loses its capacity to self-renew and once matured is unable to do so at all (terminal differentiation) (see Figure 1.1).
Figure 1.1 Relationships between the various types of cell involved in haemopoiesis (from Hughes-Jones et al. 2009).Reprinted with permission of John Wiley & Sons, Inc.
Growth factors are naturally occurring glycoproteins and determine the behaviour of the stem cell. They are produced from a number of sources: macrophages, fibroblasts, endothelial cells, monocytes, T-cells, the kidneys and the liver (Pallister 2005). Growth factors can work solely on a committed line such as erythropoietin. Others are synergistic, whilst others can influence both early progenitor cells and later committed cells. Granulocyte colony stimulating factor (G-CSF) and thrombopoietin (TPO) enhance the activities of stem cell factor (SCF), interleukin-3 (IL-3), granulocyte monocyte-colony stimulating factor (GM-CSF). In addition, G-CSF and GM-CSF enhance the function of mature cells (Hoffbrand et al. 2004; Metcalf and Nicola 1995). Our understanding of the activities of growth factors has aided in the pharmacological production of erythropoietin used in renal disease and recombinant granulocyte stimulating factor, (rHG-CSF), used in stem cell transplantation to reduce the period of neutropenia. Table 1.1 provides an overview of growth factors, their sources and functions.
Table 1.1 Overview of growth factors, source and activities (adapted from Pallister 2005 and Hoffbrand et al . 2004 ).
The microenvironment of the bone marrow is known as bone marrow stroma and is a unique environment which forms the structural base, allowing stem cells to grow and develop. The stroma is made up of a structural base of cells which are macrophages, reticular connective tissue, osteoclasts, osteoblasts, adipocytes, fibroblasts and endothelial cells which form the sinusoids. The structure also enables the generation of the mesenchymal tissue providing vessels and bones to support stem cell development. The HSC form the parenchyma cells (functioning cells) of the stroma and their close proximity with the stromal layer is essential for proliferation (Kronenwett et al. 2000). Stromal cells produce growth factors, SCF, (kit ligand, steel factor) to ensure self-renewal of those cells. In addition, the stromal cells produce adhesive proteins such as fibronectin, forming an extra-cellular matrix. These adhesive proteins allow growth factors to become attached to receptor sites on the stem cell and once attached, set off intracellular chemical reactions to prepare the stem cell to respond to the growth factor instruction, which could be to become quiescent, proliferate, become committed, differentiate or mature. The adhesive interactions between stem cells and stromal layers are key to migration, circulation and proliferation.
It has been identified that HSCs have their own ‘space’ within the bone marrow (Traynor 2006). Erythrocyte precursors lie adjacent to venous sinus in erythroblast islands and each has its own macrophage. Megakaryocytes are found next to the venous sinus and their cytoplasmic projections extend directly into the lumen. Cytoplasmic granules, which are to become platelets, congregate at the edges of the projection, making holes in the megakaryocytes (known as platelet budding) and flow into the circulation. The precursors for monocytes and granulocytes are found deep within the cavity and when they mature are very motile and migrate to the venous sinus to enter into circulation (Pallister 1997).
Stem cells’ primary home is the bone marrow, but a small percentage enter circulation. The recognition of this has led to the development of being able to collect peripheral stem cells via apheresis for ‘harvesting’ and transplantation. Circulating progenitor cells form part of the self-renewal process and are able to re-populate stem cells in the bone marrow. Peripheral stem cells are known to be more mature than those in the bone marrow; when used for haemopoietic stem cell transplantation, they generally engraft earlier, leading to less time for the patient being neutropenic and hence reducing the potential for infections. See Chapter 2 and Chapter 20 for more details.
We do not as yet have the entire picture of the regulatory mechanism of HSC to understand how homeostasis is maintained within the bone marrow. Growth factors clearly up-regulate bone marrow activity but down-regulation is less well understood. The known regulatory factors are listed in Table 1.2. Ultimately, the actions of the regulators are to maintain haemopoiesis in a steady state, inhibiting mitosis or preventing apoptosis.
Table 1.2 Down-regulators of haemopoiesis.
Transforming growth factor β (TNF-β)
Prostaglandin E
Macrophage inflammatory protein 1a (MIP-1a)
α and γ interferon
Leukaemia inhibitory factor
Tumour necrosis factor -α (TNF-α)
Lactoferrin
Inhibin
Apoptosis is a key factor in maintaining homeostasis of haemopoiesis. Apoptosis is programmed cell death (PCD), equated to ‘cellular suicide’. It is regulated by a number of physiological processes leading to biochemical activities of intracellular proteins known as capases, taking place within the cell, resulting in a change in cell morphology. The morphological changes primarily are: changes to the cell membrane which cause loss of attachment, cell shrinkage, loss of membrane symmetry and blebbing. In addition, nuclear changes also occur, which include chromatin condensation, nuclear fragmentation and chromosomal DNA fragmentation (Charras et al. 2008). All these activities will ultimately lead to the death of the cell (see Figure 1.2).
Figure 1.2 Haemopoiesis, physiology and pathology (from Mehta and Hoffbrand 2009).
Reprinted with permission of John Wiley & Sons, Inc.
Myeloid lineage bone marrow cells
Erythropoiesis
Erythropoiesis is the name for red blood cell production. Red blood cells are the most numerous of all marrow cells, as indicated in Table 1.3. Their production is triggered by hypoxia. When the blood enters the kidneys, hypoxia triggers erythropoietin (EPO) release. It is a glycoprotein synthesised by the peritubular interstitial cells of the kidneys, and chromosome 7 carries the gene for its coding (Pallister 1997).
Table 1.3 Normal values and functions of cells.
Marrow cell
Normal count
Overview of function
Red blood cells
Women 4–5 x 10¹²/LMen 5–5.5 x 10¹²/L
Gaseous exchange
White cell count (WCC)
4–11/10
9
/L
Fight infections
Platelets
150–400
9
/L
Instigates haemostasis
Erythrocytes develop and mature in the bone marrow and Figure 1.3 is a schematic representation of the stages of their development. Receptor sites for EPO are found on BFU-E, CFU-E and pronormoblasts. Erythropoietin shortens the pronormoblast phase, enabling faster production of red blood cells.
Figure 1.3 Development of erythrocytes.
Development starts from the CFU-GEMM to BFU-E, progressing to CFU-E, which develops into the first recognisable erythroid precursor, the pronormoblast. Under Ramonsky staining the pronormoblast appears blue due to RNA ribosomes (Turgeon 2005). It has a very large nucleus to cytoplasm ratio. As it continues through stages of development, it becomes increasingly smaller in size, the haemoglobin concentration increases, giving the cell a pink colour. The nucleus is eventually ejected at the late normoblastic phase when it then becomes known as the marrow reticulocyte. The reticulocyte stage continues for a further 1–2 days in the marrow, losing its RNA, further increasing the concentration of the haemoglobin. Reticulocytes circulate in the blood for a further 1–2 days to mature into erythrocytes. The process of maturation from pronormoblast to erythrocyte can take approximately five days and the lifespan for a normal red blood cell is 120 days (Lewis et al. 2001). Reticulocytosis tends to be an indication of either excessive haemolysis (as seen, for example, in sickle cell disease and thalassaemia) or excessive haemorrhage.
Erythrocytes are anucleated, biconcave in shape, which provides a greater surface area for their function of gaseous exchange: taking oxygen (O2) from the lungs to the tissues and carbon dioxide (CO2) from the tissues to the lungs. The ability of the erythrocyte to carry out its function is made possible by the haemoprotein, haemoglobin, and each erythrocyte has approximately 600 million haemoglobin molecules. The lack of nuclei and organelles also contributes to increased haemoglobin content and gas-carrying capacity. Approximately one half of the CO2 is directly bound to haemoglobin. The rest is converted by the enzyme carbonic anhydrase, which is found in erythrocytes, into bicarbonate ions that diffuse back out into the plasma and hydrogen ions (H+) that bind to the protein portion of the haemoglobin, thereby keeping the pH of the erythrocyte, relatively neutral.
Erythrocytes are able to make energy from breaking down glucose, known as glycolysis. This process involves enzymatic activity, which occurs along two chemical pathways known as the Embden-Meyerhof pathway (EMP) (95% of glycolysis takes place along this pathway) and pentose phosphate pathway (PPP).
Erythrocytes have structural and contractile proteins which make up the cytoskeleton. These proteins are α and β spectrin, ankyrin, actin protein 4.1 and enable erythrocytes to be deformable and flexible (Lewis et al. 2001). Erythrocytes have a diameter of 6–7 µm approximately and they have to pass through microvessels, which can have a diameter of 3 µm. Therefore deformability is crucial to their ability to travel to tissues. Defects of any of these proteins compromise the erythrocyte’s function. The most abundant of the proteins is spectrin and a lack of it leads to a condition known as hereditary spherocytosis. The surface of erythrocytes also has antigens, some of which denote the blood group an individual has inherited (see Chapter 17).
In addition to erythropoietin, erythrocytes also require nutrients and some hormones which help to influence their development. Protein is required for the cell membrane as well as being a component of haemoglobin. Iron is an essential component of haemoglobin and vitamin B12 is required for nucleic synthesis. Vitamin C increases the absorption of iron and copper acts as a catalyst for iron to be taken up by haemoglobin. Vitamin B6 is required for haemoglobin synthesis and folic acid aids in maturation. Lack of the hormone thyroxin compromises EPO production and the ‘sex’ hormones have opposing influences on erythrocyte’s development. Testosterone stimulates erythrocyte production; conversely oestrogen decreases red blood cell production. This explains why the red blood cell count is higher in men than women and why androgenic drugs are used in conditions like Fanconi’s anaemia.
The reticulo-endothelial system (RES), comprising the liver, spleen, lymph nodes and bone marrow is responsible for the destruction of senescent red blood cells. Aging red blood cells are recognised by macrophages in the RES due to a number of changes which take place. The changes are caused by a reduction in the glycolytic activity, leading to reduced activities of its essential enzymes. This has the effect of making the chemical pumps (sodium pump and magnesium pump) inside the red blood cell inefficient, allowing an increased intake of water, making it unable to deform easily. The abnormal spherical shape is detected by the macrophages, particularly in the spleen, and the red blood cell is then phagocytosed.
During this process the haemoglobin molecule is removed and the globin component is broken down into amino acids to be reused for new erythrocytes. The iron is separated from the haem and is transported by apopferritin for storage as ferritin for future use in production of erythrocytes. When iron is required for erythrocyte production, the plasma protein transferrin transports the ferritin to the bone marrow where developing erythroblasts have receptor sites for transferrin. The haem forms biliverdin, which converts to bilirubin and is stored as bile in the gall bladder.
Leukocytosis
The entire process of leukocyte production is not fully understood, although it is known that there are specific growth factors involved in their development (see Table 1.1 on growth factors) and the production is increased during periods of infection and inflammation.
A leukocyte’s prime function is to defend the body against and react to infective organisms and toxins. They are less numerous than erythrocytes and are nucleated. Leukocytes are divided into granulocytes (also known as polymorphonuclear cells because they are multi-nucleated and agranulocytes as indicated in Table 1.5). Granulocytes populate three environments, marrow, blood and tissues (Bainton 2001). Their movement is unidirectional, meaning they do not return to a previous environment, for example once they have left the marrow and entered circulation, they do not return to the marrow; similarly once in tissues, they do not return to circulation.
Table 1.5 Granulocytes and Agranulocytes.
Granulocytes and monocytes provide innate immunity, meaning it is present from birth, is non-specific, for example attacks many pathogens and does not require sensitisation. Lymphocytes provide acquired immunity, meaning they need to be sensitised by a specific antigen, either from an infection or vaccination and produce memory cells.
The total white cell count (WCC) can be seen in Table 1.3, but to establish the numbers of each type of white cell a differential count is required. Table 1.4 indicates the normal differential counts.
Table 1.4 Normal values of Granulocytes and granulocytes.
Adapted from (Hoffbrand et al. 2004).There may be some variations on the above results depending on the population the hospital laboratory serves.
Neutrophils *
2.5–7.5 x 10
9
/L
Basophils
0.01–0.1 x 10
9
/L
Eosinophils
0.04–0.4 x 10
9
/L
Monocytes
0.2–0.8 x 10
9
/L
Lymphocytes
1.5–3.5 x 10
9
/L
*It is well known the WCC count is lower in blacks than Caucasians, but it is not clearly understood why that occurs.
Granulocytes
Neutrophils are the most numerous of white cells and they are produced on the myeloid line in the bone marrow, from the CFU-GM committed progenitor cell, as illustrated in Figure 1.4. Both neutrophils and monocytes share the CFU-GM which is developed from the CFU-GEMM. When the CFU-GM differentiates to CFU-G this becomes committed to producing neutrophils. The production of CFU-G progenitor cell is triggered by the growth factor, G-CSF.
Figure 1.4 Neutrophil development.
The myeloblast is a large cell with a high nucleus to cytoplasm ratio, which undergoes several stages of division (as illustrated in Figure 1.4) and is the first granulocyte precursor which is recognised by cell morphology. At the promyelocyte stage primary granules are found and they contain myeloperoxidase, cathepsin G and other acid hydrolases. Secondary granules, such as lactoferrin, lysozyme and collagenase, are first seen at the myelocyte stage and in abundance in the mature neutrophil (Babior and Golde 2001).
The penultimate stage of neutrophil development is a band neutrophil. These are non-proliferating cells, and proceed to full maturation as neutrophils. Mature neutrophils are denoted by having a 3–4 lobe nucleus, held together by a thin chromatin strand and stain pink on Ramonsky staining. The whole maturity process can take up to five days, but where there is an infection, this process can be sped up to completing maturation in 48 hours. Once matured, neutrophils enter the bloodstream, making up to 60% of circulating white blood cells. Half the neutrophils will circulate and the others will loosely attach themselves to the endothelial lining of blood vessels, known as margination. This ensures there is a ready access of neutrophils to fight infections and inflammation. Neutrophils circulate for about 4–10 hours in the blood before entering tissues, where they remain for about 2–3 days, taking on the role of being non-specific against bacteria and other microbes. The daily production of neutrophils is 0.85–1.6 x 109/cells/kg/day (Babior and Golde 2001).
Neutrophils are microcytic, phagocytic cells; they are highly motile and act rapidly at the site of tissue injury and are the hallmark of acute inflammation. When active they have a limited lifespan of a few hours. They have the ability to respond to an invading organism in two critical ways: diapedesis and chemotaxis. Diapedesis is amoeboid movement. Neutrophils are able to elongate forming a pseudopodium, taking on a ‘hand-mirror’ shape to squeeze through the blood vessels and enter the interstitial tissue space. Chemotaxis is the neutrophils’ ability to detect chemicals released by pathogens and from inflammatory cytokines such as interleukin-8 (IL-8), interferon-gamma (IFN-gamma), tumour necrosis factor (TNF) and opsonins, namely the complement proteins, C3a, C5a and C6. To function efficiently neutrophils rely on being presented with the antigens and they have receptor sites for IgG and complement proteins complement C3, which coats the organism (a process known as opsonisation), making it easier for the neutrophil to engulf coated organisms (Rich et al. 2009).
When being phagocytic, the neutrophil will engulf the organism, forming a vacuole, and the secondary granules’ degranulation, releasing lysozyme, lactoferrin into the vacuole. These produce hydrogen peroxide and a highly active form of oxygen (superoxide) which ultimately leads to the death of the ingested organism.
Eosinophils
Eosinophils develop and mature in the bone marrow, being produced from the CFUeo, and go through phases of development as illustrated in Figure 1.5. The development of eosinophils is triggered in response to interleukin 3 (IL-3), interleukin-5 (IL-5) and granulocyte macrophage colony stimulating factor (GM-CSF). Mature eosinophils stain red with eosin dye using Ramonsky technique.
Figure 1.5 Development of eosinophils.
Following maturation they have large cytoplasmic granules and less than 1% circulate in blood, approximately 50% marginate like neutrophils and the rest enter tissues such as the skin and lower gastrointestinal tract. Eosinophils circulate in the blood for 8–10 hours and if not stimulated can survive for approximately 10–12 days. They are phagocytic, but not as aggressive as neutrophils. They are approximately the same size as neutrophils, but have large granules and respond to parasitic infections. They have a major role in controlling inflammatory responses, by neutralising histamine produced by basophils and mast cells. Along with mast cells they have a role to play in mechanisms involved in allergic reactions and asthma. Eosinophil count can vary with age, exercise and environmental stimuli such as allergens.
Basophils
Basophils are the least numerous of circulating white blood cells, forming 1% of their total and are non-phagocytic cells. They are produced from the CFU-baso and differentiation from basophilic promyelocyte → to myelocyte → to metamyelocyte and → final maturation. Their development takes place in the bone marrow and the growth factor, interleukin-5 (IL-5) initiates their development. Basophils are given their name because of their capacity to stain with base dyes and have a bluish-purple colouring on Ramonsky staining. They are the least understood of the white cells, but it is known that they are involved in hypersensitivity and have a role in instigating inflammatory response since they have granules containing substances such as heparin, histamine and platelet activating factor (Roitt 2001). Basophils also have receptor sites for antibody IgE and when bound to basophils, they aid the release of the above chemicals leading to inflammation and vascular permeability, enabling phagocytic cells to leave the circulation and enter interstitial tissue space to engulf and digest organisms.
Basophils are involved in hypersensitivity reactions and anaphylaxis. By binding to IgE this is thought to be a significant factor in the selective response of these cells to environmental stimuli such as pollen and and the clinical symptoms of an allergic reaction: watery eyes, runny nose and difficult breathing.
Platelets
The production of platelets starts with the CFU-meg in the bone marrow. The stage of development then proceeds from megakaryoblast to megakarocyte. The process of the development of platelets is different to that of other marrow cells as it is based on endomitotic replication (Coleman et al. 2005). Endocytosis is the doubling of chromosomes within a nucleus, but there is no nuclear division and the cytoplasm does not divide. Instead, the cytoplasm increases in volume. The replication of the chromosome within the nucleus can occur several times. As a consequence, with each cell cycle division of endomitosis the cell becomes larger. Once mitotic division has been completed, the nucleus within the megakaryocyte becomes lobulated and the cytoplasmic granules are formed to make the platelets. The control and production of platelets is regulated by the glycoprotein thrombopoietin, which is produced by the liver and kidneys. Platelets have receptor sites (C-MPL) for thrombopoietin, which removes it from circulation (Pallister 2005).
The megakaryocyte by its name indicates this is a very large cell, almost ten times the size of other marrow cells in the bone marrow, and each megakaryocyte can produce 2000–4000 platelets. Platelets are non-nucleated, disc-like structures which are formed from fragmentation of the megakaryocytic cytoplasm. They form holes in the megakaryocyte, known as platelet budding, to enter into circulation and are the second most numerous of all circulating marrow cells, as indicated in Table 1.3. Once in circulation, approximately one third are stored in the spleen, which acts as a reservoir and is able to be responsive to emergency demand. Platelets have a lifespan of 10–14 days in circulation.
Platelets are essential for maintaining haemostasis and critical in instigating the clotting cascade to stop haemorrhagic episodes. Platelets have glycoproteins on the surface which enable them to become adhesive following vascular injury and to allow aggregation and enable them to form a platelet plug. When activated, platelets release the contents of their granules into their canalicular system and into the surrounding blood, providing a reactive surface to enable plasma coagulation proteins to be absorbed. The platelets produce two types of granules: dense granules and α-granules. They are listed in Table 1.6.
Table 1.6 Types of granules produced by platelets.
Adapted from (Harrison and Cramer 1993 and George 2000).
Dense granules
α-granules
Adenosine diphosphate
Platelet factor IV
Adenosine triphosphate
Platelet derived growth factor (PDGF)
Calcium
Von Willebrand factor (vWF)
Serotonin
Heparin antagonist
Fibrinogen
Fibronectin
Coagulation factors V and X111
β-thromboglobulin
Thromboxane A2 is a powerful vasoconstrictor and aggregator. It is produced by the platelets and plays a key role in activating other platelets. The actions of the above enable the formation of the platelet plug, which instigates action from the clotting factors. Through a cascading action clotting factors are activated and along with other substances form a fibrin clot.
Disorders or abnormalities of platelets are known as thrombocytopathy: an increase in platelets is thrombocytosis, a decrease is called thrombocytopenia and a decrease in function is thrombasthenia.
Lymphoid lineage marrow cells
Agranulocytes
Lymphocytes are the second most common white blood cell, with T-lymphocytes constituting approximately 60–80% of circulating lymphocytes, B-lymphocytes making approximately 10–30% and NK cells making up 2–10% (Hughes-Jones et al. 2009). Most lymphocytes are generally small, having a diameter of about 10–20 µm, making them larger than erythrocytes but much smaller than monocytes. In lymphocytes the nucleus is round and takes up most of the cell space.
Lymphocytes are found in large numbers in the lymph nodes, spleen, thymus, tonsils and in the Peyer’s patches of the gastrointestinal tract. Unlike other blood cells which are unidirectional, some lymphocytes may leave and re-enter the circulation, surviving for about one year or more. The principal paths of re-circulating lymphocytes are through the spleen or lymph nodes (Delves and Roitt 2000). Lymphocytes enable the body to remember antigens and to distinguish self from non-self.
Lymphocytes are derived from the lymphoid multipotent stem cells in the bone marrow and provide acquired immunity. Lymphoid stem cells can divide into T or B-lymphocytes, each carrying out specific functions to defend the body against infections. Both T and B-cells travel between blood and tissues, enabling them to kill invading organisms. Differentiation between T and B-lymphocytes is based on gene rearrangements, cluster differentiation, cell membrane markers and antibody receptors (Kircher and Marquardt 2002).
T-lymphocytes
T-lymphocytes provide cellular mediated immunity and start their development in the bone marrow, continuing their maturity in the thymus gland under the influence of thymosin. T-lymphocytes develop from pro-thymocytes to mature T-lymphoblasts, becoming immunological competent. T-lymphocytes leave the thymus gland and circulate in the bloodstream to the lymph nodes and the spleen. T-lymphocytes, further subdivide into four sub-classes:
T helper cells ( CD4+)
T suppressor cells ( CD8+)
Cytotoxic T-cell (Tc)
Natural killer cells (NK cells)
T-lymphocytes recognise and respond to antigens that appear on cell membranes in association with other molecules, known as the major histocompatibility complex (MHC). They are glycoproteins that present antigens in a form that is recognised by T-lymphocytes. (See Chapter 2 on Immunology and Chapter 20 Haemopoietic stem cell transplant.)
CD4+ helper cells and CD8+ suppressor cells have the responsibility of orchestrating the specific immune response. CD4+ (helper cells) help B-cells to differentiate and mature. They also recognise (MHC) molecules, class II (HLA-D, HLA-DR). CD8+ suppressor cells turn off the immune response, suppress other lymphocyte function and they recognise MHC class I antigens (HLA-A, HLA-B, HLA-C).
Cytotoxic T-cells (Tc) have a number of roles:
Kill virally infected cells
Destroy dysfunctional cells
Destroy malignant cells
Are responsible for organ rejection in transplantation
Tc cells have receptor sites (T-cell receptors) which recognise MHC class I antigen which are bound to CD8+.
Natural killer cells (NK), as their name suggest, rid the body of any harmful organism. They are cytotoxic and the granules contain proteins such as perforin and proteases (Roitt et al. 2001). The difference between Tc and NK cells is that Tc need to recognise antigens and MHC molecules in order to mount an immunological response to get rid of the organism (Papamichail et al. 2004). NK cells do not require sensitisation; they are able to lyse antibody coated cells, hence NK cells are also called antibody dependent cytotoxic cells (ADCC) but are also capable of destroying tumour and virally infected cells without presentation by an antibody. Tc and NK cells kill on contact by undergoing blast transformation releasing highly potent lymphokines such as IL-2 which destroys the organism and attract other lymphocytes, thereby increasing killing potential (Symth et al. 2001).
Natural killer cells can also become activated in response to interferon, a macrophage derived cytokine, and they ‘hold’ the virus while the adaptive immune response is generating antigen-specific cytotoxic T-cells that can clear the infection. Ultimately, T-lymphocytes are responsible for continuous surveillance of cell surfaces for the presence of foreign antigens.
B-lymphocytes
B-lymphocytes provide humoral immunity and start and complete their development in the bone marrow. They undergo several stages of development from pre-B progenitor cells to B-lymphoblast. The name B-cell was originally derived from the bursa of Fabricius, an outpouching organ in the gastrointestinal tract found in birds. CD4+ helper cells assist in the differentiation of B-cells aiding in their maturity. Once matured, B-cells migrate in the blood and then enter organs such as the lymph nodes, spleen, marrow, tonsils and appendix. The fundamental function of B-cells is to produce antibodies against antigens. Mature B-cells produce plasma cells which secrete antibodies. B-lymphocytes have many surface receptors enabling them to bind to many antigens. When mature B-cells become sensitised they not only produce plasma cells which secrete distinct antibodies (immunoglobulins) to a specific antigen, they also produce memory cells which are the basis of immunological memory and lead to a more rapid response in the future.
Antibodies are ‘Y’ monomer structures and there are five classifications: IgG (gamma), IgA (alpha), IgE (Epsilon), IgM (Mu) and IgD (delta). Antibodies can live for many years and carry out a variety of functions including:
Attacking viruses and bacteria directly
Activating the complement system
Inactivating toxic substances
Helping phagocytic cells
Monocytes
Monocytes are the largest of the marrow cells when matured, almost twice the size of red blood cells, (averaging 15–18 micrometres), and they make up about 7% of the leukocytes. The cytoplasm contains large numbers of fine granules, and they are macrocytic phagocytic cells. In the bone marrow, monocytes develop from CFU-M, differentiating into promonocytes and then to monocytes. The nucleus is relatively big and tends to be indented or folded rather than multilobed. Monocytes leave the bone marrow and circulate in the blood for a few hours and they migrate to tissues, continuing their development. Once in tissues they are then called tissue macrophages. Unlike erythrocytes, macrophages have the capacity for cell division and therefore have a reasonably long life.
Monocytes are highly motile and capable of ingesting infectious agents, red blood cells and other large particles. They usually enter areas of inflamed tissue later than the granulocytes and often they are found at sites of chronic infections.
Macrophages are sited in parts of the body in a strategic manner to fight infection and have particular names and form the reticulo-endothelial system (RES).
Apart from being (see table 1.7) part of the above organs, macrophages are also free wandering cells, providing non-specific immunity and are able to regulate immune responses. Through their ability to phagocytose, they prepare antigens for presentation to T-lymphocytes and enable the antigen-antibody complex which can stimulate B memory cells. They have the ability to produce chemicals known as monokines (Kircher and Marguard 2002).
Table 1.7 Sites of macrophages.
Site
Name
Skin
Langerhans cells
Spleen
Lattoral cells
Liver
Kupffer cells
Lungs
Alveolar macrophages
Brain
Microglia
Bones
Osteoclasts
Kidneys
Glomerulus mesanahgial cells
Lymphoid
Medullary sinus
Apart from their role as scavengers, macrophages play a key role in immunity by ingesting antigens, old faulty cells, microscopic particles and processing them so that they can be recognized as foreign substances by lymphocytes, thereby taking on the role of antigen presenting cells (APC). Macrophages have the ability to ingest not only other cells but also many other microscopic particles.
Conclusion
Haemopoiesis is a fascinating system, involving many complex processes to produce marrow cells. The process takes place within quite narrow margins and it is therefore not surprising that any fault within the system can in some conditions, like acute leukaemia, manifest symptoms quickly.
The continual growth in our understanding of the behaviour and action of stem cells and growth factors will impact on therapeutic modalities.
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Chapter 2
Immunology
Jane Richardson and Tracey Cutler
The aim of this chapter is to discuss the physiology of the immune system and how it can be applied in haematology nursing. By the end of reading this chapter you will:
Have an overview of the immune systemBe able to consider the impact treatment has on the normal immune responseBe able to consider the importance of early recognition of infectionWhat does the immune system do?
The internal environment of the body is maintained by homeostasis so that it is warm and moist, with a good supply of nutrients. This is an ideal environment for body cells to grow and to perform their specialist functions efficiently. However, this can also provide suitable conditions in which many types of microorganism are also able to grow and multiply. The immune system acts to resist infection by disease-causing (pathogenic) microorganisms including bacteria, viruses, parasites, fungi and yeast. The immune system may also act to maintain useful bacteria in their appropriate locations.
Friendly bacteria
The human body contains many useful microorganisms (sometimes known as ‘friendly’ bacteria). In fact, it has been estimated that a typical adult body contains ten times more bacterial cells than body cells (Manas et al. 2003). Most of these are symbiotic bacteria that benefit from living in or on the human body, but are also beneficial to it. Most of these bacteria are either on the outside of the body where they colonise the skin surface, oral mucosa and the vaginal mucosa, or in the gut where they colonise the lower intestine, particularly the colon. The gut may contain more than a trillion bacteria from around 400 different species (Hammerman et al. 2006). In these locations the friendly bacteria form a complex ecosystem or microflora which has a variety of health benefits (O’Hara and Shanahan 2006). One major benefit is that the presence of the friendly bacteria inhibit colonisation by pathogenic species. This may be achieved by preventing pathogenic bacteria from attaching to the gut wall or by producing substances that act as local antibiotics (Berger 2002). Resident bacteria may also inhibit pathogens by competing more successfully for space or nutrients, or by producing acid conditions which inhibit the growth of many other species. Lactobacillus bacteria on the vaginal mucosa produce acid conditions that inhibit the growth of other microorganisms (Gould and Brooker 2000). Some of the friendly gut bacteria in particular are also helpful as they ferment undigested or partially digested food in the colon, producing useful products such as vitamin K and short chain fatty acids which are absorbed and used (O’Hara and Shanahan 2006).
The use of antibiotics in a patient to kill or inhibit bacteria causing an infection may also kill some of the friendly bacteria. This is likely to disturb the delicate resident bacterial ecosystem. Until the microflora is able to re-establish itself, this is likely to lead to an increased susceptibility to infections in these locations (Berger 2002).
Friendly bacteria are usually only friendly if they remain in the appropriate location in the body. If gut bacteria are able to migrate through the gut wall, for example, they may be able to cause systemic infection. The gut wall is usually protected from invasion by gut bacteria by the single cell layer of the mucosal epithelium (O’Hara and Shanahan 2006) and by the presence of gut-associated lymphoid tissue (GALT) in nodules within the mucosa and submucosa layers (Gibney et al. 2003; Stagg et al. 2003) (see Figure 2.1).
Figure 2.1 Diagram to show the structure of the gut wall in the large intestine (from Tortora and Grabowski 2000).Reprinted with permission of John Wiley & Sons, Inc.
This is particularly relevant to patients who are undergoing radiotherapy and/or chemotherapy for haematological malignancies as two of the side effects (of radiotherapy and chemotherapy) are bone marrow suppression and mucositis (Chapel et al. 2007). Damage to the mucosal epithelial barrier can lead to mucositis. If mucositis occurs in the gastrointestinal mucosa there may be an increased risk of infection by normal gut flora passing through the usually intact barrier (Sonis 2004). For this reason many treatment protocols advocate the use of broad spectrum antibiotics as prophylactic cover against infection whilst the patient is neutropenic (NICE 2003). However, this will also disturb the normal bacterial microflora.
Friendly bacteria are present in many food products such as yogurt and are widely eaten. Some studies have shown that yogurt consumption is beneficial to gut health (Adolfsson et al. 2004). Many new food products also contain prebiotics and probiotics to enhance gut health. Prebiotics are food ingredients that pass through the small intestine and into the colon where they provide a nutrient source to enhance the growth and development of friendly bacteria species such as Bifidobacteria and Lactobacillus. This boosts the natural populations of gut bacteria and may help to re-establish the microflora if it has become disturbed during an infection or following treatment. Probiotics are foods containing friendly bacteria. They may be useful to reduce diarrhoea associated with antibiotic use (Adolfsson et al. 2004) by enhancing natural immunity and accelerating the recolonisation of the gut after antibiotic therapy.
This is an important issue to consider when patients are undergoing chemotherapy or radiotherapy as there is some debate whether patients who are receiving broad spectrum antibiotics need to have a restricted (low microbial) diet. The opinion is that the broad spectrum antibiotics will also affect the ‘friendly’ bacteria, lowering the body’s natural defences. Foods which are thought to be an issue are the ones avoided during pregnancy, for example live yoghurts and soft cheeses.
Many friendly bacteria are also present on the skin surface, where they may protect it from pathogens. The resident microflora may include species that are harmless when carried on the surface of healthy skin, but may cause infection if they are able to penetrate the skin surface, for example through a wound (Chiller et al. 2001). The skin surface can also support the growth of pathogens such as Staphylococcus aureus and Streptococcus pyogenes.
Haematology patients will require regular blood tests, bone marrow aspiration and trephine biopsies. If they require treatment, cannulation will be a necessity and, if treatment is long term, central venous access devices (CVAD) may be inserted. All of these procedures will break the intact skin barrier and therefore all require strict aseptic technique to prevent the entry of pathogens (Wilkes and Barton-Burke 2008). CVADs also increase the risk of infection as they are often in situ long term, which provides the potential for entry of pathogens directly into the bloodstream.
Innate immunity
There are two types of immunity that interact to protect the body. These are:
Innate (natural) immunity
Acquired (specific) immunity
Innate (inborn) immunity, as its name suggests, is present from birth. It is genetically determined and is due to a number of non-specific mechanisms that interact to protect the body from a variety of threats from the environment, including microorganisms. It consists of two lines of defence: the barriers and cellular mechanisms.
The barriers to infection
The body is protected by a system of physical and chemical barriers that prevent microorganisms from entering into its interior. The most important of these is healthy intact skin as there are very few microorganisms that are able to penetrate through this physical barrier. Skin cells are protected by the presence of the protein keratin and their continuous loss by shedding at the surface removes microorganisms (Chiller et al. 2003). Sebaceous and sweat glands in the skin produce acid secretions which can inhibit bacterial growth, while the skin surface microflora inhibits the growth of pathogens (see previous section) (see Figure 2.2).
Figure 2.2 The structure of the skin (from Tortora and Grabowski 2000 ).Reprinted with permission of John Wiley & Sons, Inc.
