Blood Biochemistry

184 Pages·1982·3.92 MB·English

by  N. J. Russell, G. M. Powell, J. G. Jones, P. J. Winterburn, J. M. Basford (auth.)

BLOOD BIOCHEMISTRY
CROOM HELM BIOLOGY IN MEDICINE SERIES
STEROID HORMONES
D.B. Gower
NEUROTRANSMITTERS AND DRUGS
Zygmunt L. Kruk and Christopher J. Pycock
DEVELOPMENT, GROWTH AND AGEING
Edited by Nicholas Carter
INBORN ERRORS OF METABOLlSM
Edited by Roland Ellis
MEMBRANE PHYSIOLOGY AND CELL EXCITATION
Bruce Hendry
THE BIOCHEMISTRY AND PHARMACOLOGY OF
ANTIBACTERIAL AGENTS
R.A.D. Williams and Z.L. Kruk
Blood Biochemistry
N.J. Russell, G.M. Powell, J.G. Jones,
P.J. Winterburn and J.M. Basford
qp
CROOM HELM
London & Canberra
© 1982 N.J. RusseU, G.M. Powel!, J.G. Jones, P.J. Winterburn and J .M. Basford
Softcover reprint of the hardcover 1s t edition 1982
Croom Helm Ud, Provident House, Burrel! Row,
Beckenham, Kent BR3 lAT
British Library Cataloguing in Publication Data
Blood biochemistry. - (Croom Helm biology in
medicine series)
1. Blood - Chemistry
I. Russel!, N.J.
621 '.11 QP93
ISBN 978-94-011-7894-5 ISBN 978-94-011-7892-1 (eBook)
DOI 10.1007/978-94-011-7892-1
Set by Hope Services, Abingdon
CONTENTS
Preface
Acknowledgements
l. Introduction 2
2. Red Blood Cells 4
3. Haemoglobin: Structure and Function 21
4. Haemoglobin: Synthesis and Degradation 37
5. The Anaemias 50
6. White Blood Cells and the Immune Response 68
7. Immunoglobulins and Complement 90
8. Blood and Tissue Antigens 104
9. Haemostasis 116
10. The Blood Buffering Systems 131
1l. Blood as a Transport System 137
12. The Collection, Separation and Analysis of Blood
and its Components 147
13. Perspectives 168
Index 173
PREFACE
The idea for this book arose from an integrated Iecture course on the
biochemistry of blood given to medical students in the second year
of their pre-clinical studies. However, the material in that course
has been expanded and it is intended that the book provide both the
medical and non-medical reader with a concise and up-to-date account
of the status of knowiedge of the biochemistry of blood. A glance at
the chapter titles shows how wide a field this covers, including many
of the growth areas in biochemistry.
It is assumed that readers of the book will have a basic knowiedge
of biochemistry. A functional approach is, adopted, and whenever
possible the material is organised in terms of biochemical functions,
although there are separate chapters on the white cell and the red cello
Because of the clinical importance of analysing blood components
and assaying enzymes in the diagnosis of disease, chapters are included
on the separation, preparation and measurement of blood components.
In order to assist in bridging the gap between scientific studies and
medicine, examples are included of changes associated with various
diseases when the biochemistry is weil understood. Attention also has
been drawn to those areas where re cent research in blood biochemistry
has resulted in major advances in our understanding of fields having Iess
obvious clinical relevance. It is hoped that these inclusions will stimulate
interest and illustrate that such basic research is essential to the proper
understanding of the functioning ofblood in health and disease.
AC KNOWLEDG EME NTS
We are grateful to Professor K.S. Dodgson for his support, and to
Barbara Power and Jean Mitchell for typing the manuscript. We should
also like to thank many of our colleagues for their helpful advice and
in particular Professor G. EIder and Drs A. Cryer, c.G. Curtis, R. EccIes,
R. John and M. Worwood.
1
INTRODUCTION
Blood has long held special significance for Man, assuming social and
religious irnportance in many cultures. The ancient Greeks recognised
that blood pulsated within vessels, and Aristotle taught that the heart
was the centre of Man's body, its seat of life, from which all desires,
feelings and emotions arose. The four chief fluids of the body were
considered to be blood, yellow bile, black bile and phlegm, their balance
determining the physical and mental qualities of the individual. A
predominance of blood represented a sanguine [sie] temperament
which, during the Middle Ages, was viewed with such special favour that,
in pictorial representations, God was often given a ruddy complexion.
William Harvey, during the seventeenth century, was the first to describe
the circulation of the blood. He believed that blood was a uniform
substance but, despite the inaccuracy of this belief, by recognising that
blood circulated, Harvey paved the way for our present understanding
of the complex composition and diverse functions of blood.
Vertebrates possess a high pressure blood system with a fast flow
rate, which not only imposes some restrictions on certain components
of blood, but facilitates a whole range of biochemical and physiological
functions. For instance, in order that blood might flow at such a fast
rate the red cell membrane must be flexible. A long-standing fascination
about the biconcave shape of erythrocytes has led to fundamental
discoveries of the molecular structure and function of the red cell
membrane and membranes in general, as weIl as providing specific
information on the mechanism of erythrocyte deformability and
membrane alterations in ageing and disease. The rapid circulation
of blood throughout the body provides an excellent 'postal system',
allowing the speedy delivery of messages such as hormones from one
organ to another, so co-ordinating the activities of different tissues.
The general functions of blood are in metabolism and its regulation,
transport, osmotic balance and defence. The metabolic and transport
roles of blood overlap to some extent, for instance in the carriage of
oxygen and carbon dioxide. Studies on the structure and function of
haemoglobin have been particularly fruitful areas of research, providing
an enormous amount of information about such diverse fields as sub
unit interactions in multimeric proteins, protein biosynthesis and the
structure of genes. This knowledge has led to biochemical explanations
2
Introduction 3
of several anaemias and molecular interpretations of some abnormal
haemoglobins. Another aspect in which transport and metabolie func
tions are intimately linked is in the movement of metabolites. For
example, glucose is utilised as an energy source by the cells within
blood and is converted to pyruvate and lactate, which are returned to
the liver for further metabolism. The important function of osmo
regulation is yet another example of the blood functioning in both
transport and metabolie capacities.
Blood plays an important part in the body's defence mechanisms.
The immune response system is able to recognise foreign material
within the body and a sequence of events is triggered that neutralises
and destroys the foreign material. There are many re cent advances in
our knowledge of the biochemistry of these processes, such as the
discovery only a few years aga of the human leucocyte antigen (HLA)
system, the functions and significance of which are only just beginning
to be appreciated. Efficient haemostasis is apre-requisite of a high
pressure circulation with a fast flow rate. Haemostasis minimises
blood loss due to injury and prevents the entry of pathogens into the
body. The practical importance of recent advances in some areas may
not be immediately obvious; however, in other instances the significance
is clearer. For example, once it had been realised that proteolysis was
involved in blood coagulation, a better comprehension of the underlying
enzymology opened up the possibility ofimproved anti-thrombotic drugs.
The complex composition of blood is not constant, but changes
during stress, starvation, exercise and as the result of injury or disease.
The fact that it is relatively simple to obtain blood sampIes and that
blood composition refIects the overall state of the body has resulted
in the widespread use of blood analysis as an aid to diagnosis. The
analysis of various blood components, such as cells, proteins, metabo
lites and ions, and the assay of enzymes, provide useful information
for the clinician. Proliferation of the number of parameters that can be
measured and the pressure to process large numbers of sam pIes rapidly
has led to increasing automation. A highly competitive industry aimed
at providing reliable biochemical tests that can be used as diagnostic
aids has developed around the application of biochemical techniques
to the separation and measurement of blood components.
2
RED BLOOD CELLS
Introduction
The red blood cell, or erythrocyte, possesses a most unusual cell shape.
The discoid form, together with a distinctive red colouration, makes it
one of the most easily recognised cell types in the body. It is also
probably the most studied cello
Adult blood contains 4.5-5.8 X 1011 red blood cells per decilitre,
with males generally having higher cell counts than females; these
values correspond to haemoglobin contents of 14-15.5 gJdl blood.
Using these figures it can be calculated that the haemoglobin concen
tration inside the red cell is extremely high, being approximately 35
per cent (wJv). A decrease in either the number of red cells or their
haemoglobin content produces a condition known as anaemia (see
Chapter 5).
Cell Shape and Deformability
The discoid shape provides a large surface area to volume ratio and a
thin cross-section, so that no haemoglobin molecule is more than 1 J.lm
from the cell membrane. Consequently, the diffusion path for oxygen
and carbon dioxide is short, which is an irnportant factor in the major
function of the red cell, namely gas carriage. Although red cells are
approximately 8 J.lm in diameter, by deforming their shape they can pass
through capillaries in the peripheral circulation that are considerably
less than this size. The smallest pore size is encountered in the spleen.
Blood ente ring the spleen from the Bilroth cords is forced through the
endothelial cell basement membranes via slits 3.5 J.lm in diameter,
which act as filters. During this process, although the shape of the red
cell is deformed, the cell membrane is not stretched. The fact that
red cells are able to deform rather than behave like rigid particles leads
to blood behaving as a non-Newtonian fluid: its viscosity decreases as
meer forces are applied. If red cells were not flexible blood would be
far more viscous; in fact it is doubtful that it could flow at all. This
flexibility is a property of the cell membrane.
Life Cycle
Red cells are made in bone marrow, where they arise from stern cells
4