BIOLOGY STUDY GUIDE 1-4

f

BIOLOGY STUDY GUIDE I

Revised Nuffield Advanced Science

N12402

General editor, Revised Nuffield Advanced Biology Grace Monger

Editors of Part One, 'Maintenance of the organism' Tim Turvey Colin Wood-Robinson

Editors of Part Two, 'Control and co-ordination in organisms' Grace Monger M. B. V. Roberts

Contributors to this bookProfessor Dennis BakerDr D. A. BrodieProfessor Patrick J. ButlerElizabeth FenwickDr Peter FenwickDr I. D. FraserProfessor J. L. HallCarolyn HallidayDr Tim HallidayDr J. W. HannayDr Patricia KohnDr Peter KohnProfessor Rachel M. LeechDonald B. LongmoreProfessor Hans MeidnerGrace MongerDr David J. PattersonM. B. V. RobertsProfessor G. R. SagarDr N. C. Craig SharpDr Richard SmithTim TurveyDr Antony J. Wing •••••'.Colin Wood-Robinson

The General Editor would like to acknowledge with thanks the helpful advice of Professor A. P. M. Lockwood on Chapter 10.

The Nuffield-Chelsea Curriculum Trust is grateful to the authors and editors of the first edition:

Organizers, P. J. Kelly, W. H. Dowdeswell; Editors, John A. Barker, John H. Gray, P. J. Kelly, Margaret K. Sands, C. F. Stoneman; Contributors, John A. Barker, L. C. Comber, J. F. Eggleston, Dr P. Fleetwood-Walker, W. H. Freeman, Peter Fry, Dr R. Gliddon, John H. Gray, Stephen W. Hurry, P. J. Kelly, R. E. Lister, Dr R. Lowery, Diana E. Manuel, Brian Mowl, M. B. V. Roberts, Margaret K. Sands, C. F. Stoneman, K. O. Turner, Dr A. Upshall.

BIOLOGY STUDY GUIDE I

PART ONE MAINTENANCE OF THE ORGANISM

PARTTWO CONTROL AND CO-ORDINATION IN ORGANISMS

Revised Nuffield Advanced SciencePublished for the Nuffield-Chelsea Curriculum Trust by Longman Group Limited

Longman Group LimitedLongman House, Burnt Mill, Harlow, Essex CM20 2JE, England and Associated Companies throughout the World

First published 1970Revised edition first published 1985Copyright © 1970, 1985. The Nuffield-Chelsea Curriculum Trust

Design and art direction by Ivan Dodd New diagrams by Oxford Illustrators Limited

Filmset in Times Roman and Universand made and printed in Great Britainby Hazell Watson & Viney Limited, Aylesbury

ISBN 0 582 35431 5

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means - electronic, mechanical, photocopying, or otherwise - without the prior written permission of the Publishers.

The Nuffield-Chelsea Curriculum Trust acknowledges with thanks the permission granted by the Joint Matriculation Board for the reproduction of some questions from past Nuffield Advanced Biology examination papers.

NATIONAL

CENTRE

Cover photograph

Scales on the wing of a tortoiseshell butterfly, Aglais urticae.

Nick Taylor/London Scientific Films Ltd.

IV

CONTENTS

Foreword page vi

To the students who use this book viii

Part One MAINTENANCE OF THE ORGANISM

Chapter 1 Gas exchange page 1

Chapter 2 Breathing and gas exchange in Man 14

Chapter 3 The circulatory systems of animals and plants 39

Chapter 4 Blood and the transport of oxygen 86

ChapterB Cells and chemical reactions 120

Chapter 6 Heterotrophic nutrition 164

Chapter? Photosynthesis 211

Part Two CONTROL AND CO-ORDINATION IN ORGANISMS

Chapter 8 The plant and water 245

Chapter 9 The cell and water 264

Chapter 10 Control by the organism 281

Chapter 11 Co-ordination and communication 319

Chapter 12 The response to stimuli 356

Chapter 13 Behaviour 388

Chapter 14 The human brain and the mind 426

Index 462

FOREWORD

When the Nuffield Advanced Science series first appeared on the market in 1970, they were rapidly accepted as a notable contribution to the choices for the sixth form science curriculum. Devised by experienced teachers working in consultation with the universities and examination boards, and subjected to extensive trials in schools before publication, they introduced a new element of intellectual excitement into the work of A-level students. Though the period since publication has seen many debates on the sixth form curriculum, it is now clear that the Advanced Level framework of education will be with us for some years in its established form. That period saw various proposals for change in structure which were not accepted but the debate to which we contributed encouraged us to start looking at the scope and aims of our A-level courses and at the ways they were being used in schools. Much of value was learned during those investigations and has been extremely useful in the planning of the present revision. The time since first publication has also seen a remarkable expansion in the number of candidates taking A-level biology and it is encouraging to us to know that we helped in this development.

The revision of the biology series under the general editorship of Grace Monger has been conducted with the help of a committee under the chairmanship of Arthur Lucas, Professor of Curriculum Studies, CSME, Chelsea College, University of London. We are grateful to him and to the committee. We also owe a considerable debt to the Joint Matriculation Board which for many years has been responsible for the special Nuffield examinations in biology, and to the representatives of the Board who sat on the advisory committee and who have given help in many other ways.

The Nuffield-Chelsea Curriculum Trust is also grateful for the advice and recommendations received from its Advisory Committee, a body containing representatives from the teaching profession, the Association for Science Education, Her Majesty's Inspectorate, universities, and local authority advisers; the committee is under the chairmanship of Professor P. J. Black, academic adviser to the Trust.

Our appreciation also goes to the editors and authors of the first edition of Nuffield Advanced Biological Science, who worked under the joint direction of W. H. Dowdeswell and P. J. Kelly, the project organizers. Their team of editors and writers included John A. Barker, John H. Gray, Margaret K. Sands, and C. F. Stoneman. The present revision has only been possible because of their original work.

I particularly wish to record our gratitude to Grace Monger, the General Editor of the revision. This is the second occasion on which we have asked her to undertake the revision of one of our biology series, as she was responsible for the highly successful O-level Biology revision. We are therefore doubly grateful to Miss C. M. Holland, Headmistress of the Holt School, Wokingham and the Berkshire Education Authority

vi Foreword

for agreeing to her secondment. Grace Monger has had a particularly onerous task because the many topics that biology covers have been subject to an exceptional number of changes and new discoveries in recent years. She and her team of editors have been fortunate in being able to draw on the help, as writers and consultants, of experts in their fields in universities, teaching hospitals, and other institutions of learning. To Grace Monger and her editors, John A. Barker, T. J. King, M. B. V. Roberts, lanto Stevens, Tim Turvey, and Colin Wood- Robinson, and to the many contributors, we offer our most sincere thanks.

I would also like to acknowledge the work of William Anderson, publications manager to the Trust, his colleagues, and our publishers, the Longman Group, for their assistance in the publication of these books. The editorial and publishing skills they contribute are essential to effective curriculum development.

K. W. KeohaneChairman, Nuffield-Chelsea Curriculum Trust

Foreword vii

TO THE STUDENTS WHO USE THIS BOOK

This Study guide is one of the revised Nuffield Advanced Biology publications. It continues a special approach to biology which was developed in the original edition first published in 1970. Through this approach it was hoped that students would gain a broad knowledge of biological science, an understanding of the processes by which biologists acquire knowledge, and awareness of the significance of the subject to human society. It was also hoped that the publications would give students the opportunity to apply the knowledge they gained, in a creative manner.

In writing the new edition the editors have been able to draw on the experience of many teachers and students who have used the first edition. They found that the approach of the, first edition was successful in developing an understanding of biological principles and they also found that there were several ways in which students could make better use of the materials. These suggestions and improvements have been incorporated in the new publications.

The Study guide now contains substantial passages of descriptive text on a range of biological subjects, in addition to a collection of biological data which are presented as Study items. The different kinds of investigation will provide you with experience in:

1 Critical reading, writing, and discussion on biological issues.2 Making observations and asking relevant questions about them.3 Analysing data and drawing conclusions from them.4 Handling quantitative information and assessing error.5 Working out hypotheses and assessing those proposed by others.6 Designing investigations.7 Evaluating the implications of biological knowledge for society.

Whatever method is used to establish a concept the intention is the same - that it should lead to an understanding of that concept. Questions are asked in the text as well as in Study items and we hope you will be stimulated to ask further questions and so learn more about the subject.

The Study guide inevitably contains data collected by other people; your own practical investigations will enable you to collect data for yourselves. Suggestions for relevant practical investigations are in a series of Practical guides which are cross-referenced to the Study guide so that knowledge gained from these two sources can be linked.

It is inevitable, in studying any subject, to view it initially as a series of topics. It is nevertheless important, from time to time, to stop and take a broader view and to see how topics are related and what underlying principles apply to them all. The following questions should help you make these connections.

Vlll To the students who use this book

1 To what extent are organisms similar and different?2 How are organisms adapted in their environment?3 How are the matter and energy contained in organisms obtained,

utilized, and replaced in relation to the environment of the organisms?4 How does an organism function as a whole?5 How are the structure of organisms related to their functions?6 How do organisms maintain themselves in a balanced state both

within themselves and with their environment?7 How is one generation of organisms related to the next?8 How do organisms develop?9 What are the features of biological investigations?

10 How is biological research affected by the people who undertake itand the society in which they live?1T In what way do the findings of research biologists influencesociety?12 How can you link work in biological science with that in other subjects?13 How has biological knowledge developed in the past and how is it developing now?

It is worth remembering that to arrive at a satisfactory answer one must ask the right question. When using this Study guide and when carrying out the relevant practical investigations we hope you will ask many questions and find their answers. Above all, we hope that as a result of using these materials you will find the study of biology a satisfying and exciting experience, and one that will continue to interest and fascinate you.

Grace Monger General editor

To the students who use this book ix

PART ONE MAINTENANCE OF THE ORGANISM

NoteThroughout this Study guide the end of a Study item is indicated by the symbol D-

CHAPTERi GAS EXCHANGE

Introduction

In this book you are introduced to some of the ways of acquiring an understanding and knowledge of biology. For instance, it contains some straightforward descriptive accounts of biological phenomena for you to read. As well as this you are presented with data collected by other people, and by studying and analysing such data you should be able to deduce the underlying principles and to establish some new facts. The questions asked are designed with this in mind.

It is, however, desirable that you collect as much information as possible for yourself through carrying out practical investigations. You can then study and analyse your own observations and measurements in order to increase your knowledge and to further your understanding of biological principles. This will also reinforce your appreciation of the data that are provided for you in this book. The instructions for carrying out the practical exercises are given in the Practical guides.

There are, of course, other ways of developing your understanding of biological ideas and of adding to and reinforcing your knowledge; discussion with other people is one of them. The aim of this book is to provide a means by which you will gain a greater appreciation and understanding of biological principles and ways of thinking, and to provide a body of biological knowledge to illustrate them.

Gaseous exchange with the environment is a basic requirement of every aerobic organism, in order that the cells may obtain the gases they require for metabolism and eliminate gaseous metabolic wastes. In aerobic respiration these gases are, respectively, oxygen and carbon dioxide. Gaseous exchange depends upon there being a gradient of concentration so that the gases can diffuse from regions where they are abundant to regions where they are relatively scarce. In the simplest single-celled organism a gradient has to be maintained between the environment in which it lives and the sites within its cytoplasm requiring oxygen or producing carbon dioxide. In small organisms the external surface is used for gas exchange but there are many other, more specialized surfaces in animals and plants used for this purpose. The following sections examine such surfaces in a variety of organisms and investigate how some of them function.

1.1 Gas exchange in plants

The leaves, stems, and roots of plants are organs which perform a multitude of specialized functions. They contain living tissue made up of cells which respire aerobically. There has therefore to be a supply of oxygen to individual cells within these organs and yet there is no specialized transport system within the plant that is capable of distributing it. One might therefore expect to find that the position of living cells in these organs is more or less superficial, or that the organ is

permeated by a network of air-filled spaces, or even both. (See figure 158 in this Guide and figures 4 and 35 in Practical guide 1.)

a To what extent are these expectations met by the structure of the stem and leaves of a typical plant ?

The mesophyll cells in the leaf of a plant such as privet (Ligustrum) are loosely packed and air diffuses readily, although slowly, throughout the interior of the leaf. The leaf is covered by a more or less impervious outer layer in order to minimize water loss, and yet it has to have a means of allowing the oxygen required for respiration to diffuse into its air spaces. Thus it has minute pores called stomata in the epidermis (see figures 1 and 183). The size of a stoma can vary with changing environmental conditions, from nil to a maximum which might be 1-10 um in width and 10-20 urn in length. Much work has been done to try to understand the biological and physical properties of stomata. We shall concentrate briefly on one aspect of their structure; in a later chapter you will examine their physiology more closely. (See page 258.)

STUDY ITEM1.11 The diffusion of a gas through holes of different diameters

Table 1 gives two rather different measures of the diffusion of a gas through small holes.

Diameter Volume of CO 2 Volume of CO 2of hole diffusing per hour diffusing per square cm of(mm) (cm 3 ) hole per hour (cm 3 )

22.70 0.24 0.0612.06 0.10 0.096.03 0.06 0.223.23 0.04 0.482.00 0.02 0.76

Table 1Diffusion of carbon dioxide through holes of different diameters. After Brown, H. T. and Escombe, F., 'Static diffusion of gases and liquids in relation to the assimilation of carbon and translocation in plants', Phil. Trans. R. Soc., 1900, B67, 193, 223-291.

a Compare the figures in columns 1 and 2 of table 1 and also those incolumns 1 and 3, by plotting two graphs with the diameter of the hole on the horizontal axis (abscissa,).

b Express in words the relation between the hole diameter and1 the volume of gas diffusing per hour2 the volume of gas diffusing per unit area of hole per hour.

As a hole gets bigger its circumference increases more slowly than its area.

2 Maintenance of the organism

Calculate the ratio of circumference-.area for the hole diameters given in table 2.

Diameter of Area of hole Circumference hole (mm) (mm 2 ) of hole (mm)

22.7012.066.033.232.00

405.50114.20

28.568.193.14

71.337.918.910.1

6.3

Table 2Circumference and surface area of holes of different diameters.

From your calculations are you able to suggest the main physical characteristic of stomata that accounts for column 3 in table 1?

It has been found by experiment that the epidermis and cuticle of leaves are very effective at preventing significant gas passage and that the stomata, on the other hand, allow gases to diffuse through them readily. (This is discussed in detail in section 8.5.) Gas molecules diffusing through a small hole will be deflected by the perimeter of the hole, the closer they are to it; the diffusion paths of all the molecules passing through a small hole thus describe a hemisphere or diffusion shell around both sides of the hole. This shell is not present in moving air but is evident if the air is still.

Figure laThe appearance of stomata.i An electronmicrograph of the surface of a leaf of Hyadnthoides non-scriptus ( x 600).Photograph, Joan Sampson and Dr B. E. Juniper, The Botany School, Oxford.

Chapter 1 Gas exchange 3

20 nmFigure la (continued')ii A scanning electronmicrograph of the surface of a leaf of Drosera capensis ( x 1600).Photograph, D. Kerr and Dr B. E. Juniper, The Botany School, Oxford.

Diffusion shells such as these will interfere if close enough together (around 10 stomatal diameters) and this interference can reduce diffusion rates. The stomata are really small holes in a septum, which in this case is the epidermis of the leaf (see figure Ib). Diffusion shells will be formed around the stomata in still air.

Stomata are understandably numerous and, although figures from one source seldom agree exactly with those from another, some typical densities are given in table 3.


high concentration

low concentration

Figure IbThe action of stomata: a diagram of a diffusion shell around a small pore in a thin membrane (septum). The lines show regions of equal gas concentration; the arrows show the direction of net movement. After James, W. 0., An introduction to plant physiology, Oxford University Press, 1973.

Plant

AppleBeechBluebellBroad beanDaffodilFrog- bit (floatingleaves)MaizeOakOatPeaSunflowerSycamoreTomato

Density (mm 2 )

Upper epidermis

1000

554065

8952

025

10085

012

Lower epidermis

220340

51280

68

068

45023

220156860130

Table 3Density of stomata (mm ~ 2 ) in upper and lower epidermis of different angiosperm leaves.

e Comment upon the densities of stomata in table 3 in relation to the type D of plant.


Although it is important for gaseous exchange to take place in a leaf, it is just as important for it to do so in the living cells in the stem of a plant. The epidermis of the stems of young, non-woody plants has stomata; in older, woody stems the epidermis is superseded by a completely impervious cork layer (the cell walls in cork tissue become impregnated with a fatty substance, suberin, which gives them their water-repellent properties). This cork is many cells thick and there are cells under it which need oxygen (the cork cambium which manufactures the cork, the vascular cambium, the phloem), so gaseous exchange is still essential. Scattered throughout this cork layer are patches of loosely packed cells called lenticels through which gases may diffuse to and from the cells within the stem. In this way direct communication between the atmosphere and actively metabolizing cells is maintained.

Figure 2a A portion of horsechestnut twig (Aesculus hippocastanum) showing the lenticels in thebark. The lenticels show up as light spots.b (opposite) A transverse section of part of a young stem of elder (Sambucus sp.),showing a lenticel. (x 230.)Photographs: a Heather Angel: b From Bracegirdle, B., and Miles, P. H., An atlas of plantstructure: Volume I, Heinemann Educational Books, 1971.


lenticel

xylerrt

phloem

cork cambium

cork

Practical investigation. Practical guide ./, investigation 1 A, 'Gas exchange in leaves'.

Before going any further, let us stop and recall the main ideas and principles that are put forward in this section of the Study guide and in Practical guide 1.

Gaseous exchange is fundamental and all living cells in plants have to have a supply of oxygen. Plant leaves have considerable internal air- filled spaces and the large numbers of small stomata, distributed in characteristic patterns, differing from place to place on the plant and from species to species, allow gases to diffuse between the atmosphere and these air-filled spaces. The principle that underlies gas exchange is that a diffusion gradient must exist and be maintained between the source of the gas and the place where it is absorbed or used (called the 'sink'). The relatively long edges of stomata compared with their pore size, the separation of individual stomata, and the air movements around the leaf all contribute to maintaining the steepness of this gradient.


1.12STUDY ITEM(Essay)

a How is a typical mesophyte leaf adapted for gaseous exchange ?

b How do internal and external factors influence the rate of gaseousD exchange in such a leaf? (J.M.B.)

afferentefferent vessel vessel

part of a gill filament

1.2 Gas exchange in animals

STUDY ITEM1.21 Gas exchange in fish

In a teleost (bony fish) the structures used for gaseous exchange are the gills. They are much folded, providing a relatively huge surface area, and have a very rich blood supply. Figure 3 shows the way in which the components of a gill are arranged under the cover of the muscular operculum. Note how each gill is made up of several gill arches, each supported by a bony rod and bearing many filaments. Each filament carries many tiny lamellae, and each of these contains a network of capillaries. It is here that gas exchange with the water takes place.

The operculum covers the gill and the cavity under it is in direct communication with the mouth (buccal cavity) of the fish.

a Suggest how the fish might maintain a continuous flow of water across the gill lamellae in the direction shown in the diagram.

The blood flow in the artery and vein of the gill filament is indicated in figure 3. Notice the direction in which blood flows in the lamellae and compare this with the direction in which water flows across the gill. This arrangement is known as a counter-flow system, in contrast to an arrangement in which the water and blood flow in the same direction. Such a system is termed a parallel-flow system. So long as a concentration gradient of oxygen exists from the water to the blood in the gill, the gas will diffuse into the blood.

b Apart from the direction of blood flow in the lamella and its very large surface area, what structural feature would you expect the lamellae to possess ?

Examine figure 4 which shows theoretical graphs of the changes in percentage saturation of the water and the blood with oxygen, during their passage across or through the gill.

Figure 3The gills of a fish are in a chamber covered by an operculum. Each gill consists of several gill arches, each one bearing rows of filaments. The filaments bear many plate-like lamellae through which a copious blood supply flows. After Randall, D. J., 'Fish physiology', Am. Zool. 8,179-189, figure 1, 1968.

Maintenance of the organism

100

75

50

25

100

75

50

25

distance along lamella

A Counter-flow system

distance along lamella

B Parallel-flow systemFigure 4

''''• A comparison of the influence of a counter-flow (A) and a parallel-flow (B) system on the percentage saturation of the blood of a fish with oxygen.

c In what way does the evidence In the graphs enable you to suggest what advantage the fish gains from employing a counter-flow system in its gill?

d What have you assumed about the flow rate of water and btood in order to answer question c?

e From the information given here can you suggest reasons why, when a fish is taken from water (which has a relatively low oxygen concentration) and put into cool air (which has a relatively high oxygen

D concentration), it very quickly dies from lack of oxygen ?

STUDY ITEM1.22 Gas exchange in locusts

Insects possess a finely branching network of tubes called tracheae, which spread throughout the body and open to the atmosphere at controllable valves called spiracles. The cuticle from which the tracheae are made is secreted by the underlying epidermal cells and, like the rest of the insect's exoskeleton, consists of complex organic molecules such as chitin (a nitrogen-containing polysaccharide), sclerotin (tanned chitin), protein, and lipid. The diameter of the tracheae in a large insect like a locust varies from a maximum of about 0.7 mm to a minimum of as little as 0.2 um in the very finest tracheoles. The cuticle lining most of the tracheal network is thickened to give rings or spirals on the inner walls of the tubes. Unlike the larger tracheae, the smallest tracheoles are quite permeable, and it is through their walls that gas exchange occurs. Their blind ends penetrate deep into muscle and other tissue so that respiring cells are in close contact with a supply of gaseous oxygen. These terminal tracheoles are not always air-filled but may contain fluid, particularly when the insect is at rest. When metabolic activity increases, water is osmotically withdrawn from these fine tubes and air takes its place.

a Explain the function that might be served by the thickened rings of cuticle in the tracheae.


In small insects there is little or no active ventilation; the whole tracheal network in larger insects, by contrast, is more or less thoroughly ventilated by body movements which compress the larger tracheae and, more important, considerably squash the air sacs. These are thin-walled sacs of large volume, which form extensions to the main tracheal trunks. If the activity of the insect increases, the amplitude and frequency of the ventilation movements also increase. Ventilation is co-ordinated with the opening and closing of the spiracles and, because of the sequence of spiracle opening, this achieves air flow through the body. Thoracic spiracles are usually open during inspiration and abdominal ones during expiration.

b How do you think sufficient oxygen supply is maintained in small insects D when there is no ventilation of the tracheal system?

Practical investigations. Practical guide 7, investigation IB, 'Dissection of the ventilation system of a locust', and investigation 1C, 'The fine structure of the ventilation system of a locust'.

STUDY ITEM1,23 (Short answer question)

A locust inside a transparent syringe was observed under a stereo- microscope. The large spiracle on the second thoracic segment opened for short periods of time and the opening or closing of this spiracle was recorded as beats. The number of beats and the number of abdominal pumping movements were counted for three consecutive intervals of 30 seconds when the locust was surrounded by (1) atmospheric air, and (2) other gases. After each set of counts the syringe was 'flushed' with atmospheric air. The results are shown in figure 5.

O---O spiracle beats

•——• abdominal pumping movementsa 35

3a« 30

«g•s25

20

15

!„

Atmos- Human Atmos- Oxygen Atmos- Carbon pheric exhaled pheric pheric dioxide

bV

Atmospheric mair

-x*l

\LP^*^

\

-

-

"

, ,

w35 f

E3a

30 -5C

25 2a•s

20 1aH

15 |«

"I•s

5 S

3z o

1 2 34 5 6 7 8 9 10 11 12 13 14 15 16 f? 1? 19 20 21 FieureS Readings at 30-second intervals

(J. M. B.)


a State the effects on abdominal pumping movements of an increase in the concentration of(\) oxygen and (2) carbon dioxide.

b From these results is it possible to explain the effect of human exhaled air on abdominal pumping movements in terms of its gaseous composition ? Explain your decision.

c / What was the purpose of the flushing technique in this investigation ? 2 Comment upon its effectiveness.

d State a possible explanation for the changes in abdominal pumping movements1 from readings 16 to 182 from readings 19 to 21.

e State a physiological advantage for the insect which may be related to D the spiracle activity during readings 16 to 18. (J.M.B.)

Practical investigation. Practical guide I. investigation ID, 'The effect of gas changes on locusts' breathing'.

1.3 Adaptations for gas exchange in mammals

Practical investigations. Practical guide 1, investigation IE, 'The breathing apparatus of mammals', and investigation IF, 'The fine structure of the lungs'.

Mammals are 'warm-blooded' (homoiothermic) and usually highly active animals. They are all air-breathing and the vast majority of them are terrestrial, living in habitats where the potential for water loss to the environment is enormous. Although many mammals are quite small, the smallest mammal is considerably larger than the smallest insect, or even the smallest fish, while the group as a whole includes some of the largest animals that have ever lived.

These features combine to give mammals one characteristic that is relevant to this consideration of gas exchange: they have a very high demand for oxygen. This oxygen demand is determined by the mammal's size and varies with its activity. A cow will need more oxygen per day than a rabbit; a baboon may use more oxygen when foraging for half an hour than a sloth will. Figure 6 illustrates another aspect of oxygen demand.

a Explain the shape of the curve in figure 6.

The lung and its ventilation mechanism provide a specialized means of obtaining oxygen from the atmosphere without incurring too great a water or temperature loss. If you examine the fine details of the structure of a mammalian lung you will see how remarkable an adaptation it really is. Its many structural and physiological features combine to promote efficient gas exchange. They all help in some way to influence the


0.01 10 100 1000

Body mass (kg) Figure 6Rates of oxygen consumption of various mammals. (The scale of the horizontal axis islogarithmic.)Adapted from Schmidt-Nielsen, K., Animal physiology: adaptation and environment, 3rdedn, Cambridge University Press, 1984.

factors that can increase or reduce the rate at which oxygen may diffuse across the respiratory surface into the organism. These factors include:

1 The rate and extent of ventilation of the surface with the oxygen- bearing medium (air or water).

2 The size of the area of the respiratory surface which is in contact with the medium.

3 The distance across which the oxygen has to diffuse in order to enter the organism's tissues.

4 The physical nature of the barrier between organism and atmosphere.

5 The direction and steepness of the oxygen gradient between organism and atmosphere.

6 The existence of a means of removal of oxygen from the vicinity of the respiratory surface after it has entered the organism.

b Comment upon the structure and operational function of the mammalian lung in relation to each of the above factors.

Summary

1 In order to respire, almost every animal and plant has to exchange gases with its environment. These organisms possess structural features which make gas exchange more efficient.

2 Any gas exchange surface needs to be large and moist and can therefore very easily lose water.


The stomata and lenticels of plants enable oxygen, carbon dioxide, andwater to cross otherwise more or less impermeable barriers (1.1).The movement of any individual gas is in accordance with its ownconcentration gradient between the environment and the tissues.Gas exchange in fish occurs in the gills and the counter-flow of bloodwithin and water over the gill lamellae maintains a steep diffusiongradient for oxygen (1.21).In insects air may penetrate directly to the internal tissues by way ofthe tracheal system (1.22). Ventilation of this system inevitably causeswater loss, and spiracles prevent that loss being excessive.In insects the frequency of ventilation movements is influencedstrongly by the composition of the gas in the tracheae (1.22).In mammals the demand for oxygen is very high. This is correlatedwith their homoiothermy (1.3).Heat loss from the surface of a mammal influences oxygen demands.

Suggestions for further reading

COMROE, J. H. The lung'. Scientific American. 214(2), 1966. OffprintNo. 1034. (Some detail about ventilation control, together with ageneral survey of lung structure and function.)HEATH, O. V. S. Carolina Biology Readers No. 37, Stomata. 2nd edn.Carolina Biological Supply Company, distributed by PackardPublishing Ltd., 1981. (A comprehensive account of the structure andfunctioning of stomata.)HUGHES, G. M. Carolina Biology Readers No. 59, The vertebrate lung.2nd edn. Carolina Biological Supply Company, distributed byPackard Publishing Ltd., 1979. (A detailed account of the structureand functioning of the mammalian lung is included.)ROBERTS, M. B. V. Biology. A functional approach. 3rd edn. Nelson,1982.WIGGLESWORTH, V. Carolina Biology Readers No. 48, Insectrespiration. Carolina Biological Supply Company, distributed byPackard Publishing Ltd., 1972. (A thorough account of the structureof the tracheal system and the mechanisms involved in ventilation andgas exchange.)


CHAPTER2 BREATHING ANDGAS EXCHANGE IN MAN

2.1 The control of breathing in humans

Every human needs a continuous supply of energy, even when completely at rest, and this requirement for energy will fluctuate as the amount of work performed by the body changes. The energy is obtained by respiration (see pages 152-160). It comes chiefly from the oxidation of carbohydrates and lipids, using oxygen obtained from the atmosphere by breathing. As might be expected, therefore, as the body's activity level fluctuates so breathing alters to match the demand for oxygen. This section examines the ways by which changes in the demand for and availability of oxygen may influence the control mechanisms of breathing, and the methods by which the rate of breathing is adjusted to match the demands.

Detecting change

Knowledge about the control of human breathing began with an investigation by J. S. Haldane in 1885 into the high death rate occurring in the overcrowded rooms of the Dundee slums, and attributed at the time largely to the presence of 'bad air'. By testing the air for bacteria, Haldane showed that micro-organisms were largely the cause, rather than the chemical composition of the air: a fact we now know to be the case. The work aroused in him an interest in the composition of air and led him to perform a variety of experiments on human breathing.

In order to appreciate the implications of this and later work it is important to understand the ways in which gas concentrations are expressed. Often we show the amount of oxygen or other gas in a mixture of gases as a percentage; this tells us the relative composition of the mixture but it does not give us any idea of the quantity of any one gas in it. In order to know that, we have to know the pressure of the gas mixture, since this determines how many moles of the gas are compressed into a unit volume of the atmosphere. Because of this direct relationship between the pressure of a gas and the number of moles that are present, we use pressure as a measure of gas concentration. Hence, at sea level, where the total atmospheric pressure is 101.3kPa, the atmosphere contains approximately 21 per cent oxygen, and this gas therefore contributes 21 per cent of the total pressure; that is, the 'partial pressure' of oxygen (the proportion of the whole atmospheric pressure that is due to the oxygen component) in this atmosphere is approximately 21.2kPa (table 4). (Partial pressure of oxygen is written as p02 .)

The same calculation may be performed for the other gases in the atmosphere. Not only that, but similar figures may be worked out for different atmospheric pressures and for different media, such as alveolar air (table 5).


Altitude Atmospheric Percentage Approximate partial pressure(m above sea pressure oxygen exerted by oxygen inlevel) (kPa) the atmosphere (kPa)

0250050007500

10000

101.374.754.038.526.4

20.9520.9520.9520.9520.95

21.215.711.3

8.15.5

Table 4The change in atmospheric pressure and partial pressure of oxygen with altitude. After de Vries, H., Physiology of exercise, Staples Press, 1967.

Gas

OxygenCarbon dioxideNitrogenWaterTotal

Amount in dryatmosphere(%)

20.930.03

79.040.00

100.00

Partial pressure indry atmosphere(kPa)

21.190.03

80.090.00

101.31

Partial pressurein alveoli(kPa)

13.335.33

76.386.27

101.31

Table 5The composition of atmospheric air and the consequent partial pressure of respiratorygases. (Measurements at sea level.)After de Vries, H., Physiology of exercise, Staples Press, 1967.

What is the relevance of the data in table 4 to mountaineers attempting to climb Mount Everest (8848 m) without oxygen?

The data in table 5 appear to suggest that the body uses nitrogen, and that it absorbs more oxygen than it releases carbon dioxide. Comment upon these observations.

What values would you expect for the partial pressures of these gases in expired air (air breathed out) ?

In work done around the beginning of this century, Haldane and his co-workers conducted a series of experiments in which the carbon dioxide and oxygen levels of inspired air (air breathed in) were altered. The graph in figure 7 shows the effect upon ventilation of increasing the amount of carbon dioxide in inspired air. (Ventilation can be denned as the total volume of air taken into the lungs in unit time, usually expressed in dm 3 per minute.)

In the original work the carbon dioxide level had been allowed to rise by making the subject continuously rebreathe the air; this also lowered the oxygen levels. So in the work on which figure 7 is based, the carbon dioxide concentration of the inspired air was increased without any accompanying change in oxygen level. (This was done by arrang ing for the subject to breathe gas mixtures of known composition.)

The change in ventilation which resulted from this treatment suggested that carbon dioxide was able to exert an influence upon the control of breathing. What about oxygen? Would that too exert some influence, since it is, after all, the raw material that is required by the


1 234567

Carbon dioxide content of inspired air (per cent)

Figure 7The changes in ventilation in human subjects as a result of increasing the carbon dioxide content of inspired air.Adapted from Keele, C. A., Neil, E., and Joels, N., Samson Wright's applied physiology, 13th edition, Oxford University Press, 1982.

body's aerobic mechanisms and since breathing is, in mammals, the only way in which it may be obtained? Using a form of spirometer it was possible to expose a subject to continually decreasing partial pressures of oxygen in inspired air whilst keeping the carbon dioxide level negligible by absorbing it with soda lime.

In such circumstances breathing continues normally until the p02 falls to about 12.7 kPa, when ventilation begins to increase. If carbon dioxide is not removed, but allowed to accumulate in the inspired air, breathing in a closed circuit remains tolerable but ventilation increases at oxygen levels below 19.3 kPa (19 per cent), and breathing becomes laboured at a level of around 16.2kPa (16 per cent).

The clear implications of this work and subsequent studies is that carbon dioxide is by far the most important factor in the regulation of ventilation. A puzzling fact is evident, however, if you re-examine figure 7. The graph is not a straight line, and thus indicates that the relation between ventilation and the p c02 of inspired air is indirect. If a graph of ventilation against the pco 2 m alveolar air is plotted, it is linear, which suggests that it is the concentration of carbon dioxide in the alveoli, rather than in inspired air, that is of paramount importance in determining the ventilation rate. In fact, increasing the carbon dioxide content of inspired air does not affect alveolar pc02 until the inspired air contains more than 5 per cent carbon dioxide. The p c02 of the blood is determined largely by the composition of the gas in the alveoli and if this is maintained at a steady level the amount of carbon dioxide in the blood will also remain unchanged. Haldane argued that breathing is normally controlled to keep the amount of carbon dioxide in the blood at a constant level.


The correlation of ventilation with the pc02 of the blood naturally raises the question of how changes in blood gas composition are detected. Work in the latter half of the century by Pappenheimer and others has suggested that the influence of the raised pc02 on the pH of the blood is the main factor. Blood is known to be thoroughly buffered against pH changes, and 'normal' blood pH is between 7.35 and 7.40. A very narrow pH range of 7.00 to 7.70 is compatible with life. When carbon dioxide is dissolved in water carbonic acid is formed and this dissociates into hydrogen ions (H + ) and hydrogen carbonate ions (HCO^). With the tissues of a healthy adult man producing the equivalent of around 330 dm 3 of carbon dioxide every day, it will be obvious that the potential for lowering pH of the blood is enormous. Thus it is important that any slight change of the pH is counteracted, and it is the increase in ventilation that plays a major part in such counteraction.

Chemical control of breathing

A variety of work has shown that the body possesses nerve cells (neurones) that are sensitive to chemical changes and are called chemoreceptors. By the use of chemoreceptors sensitive to very small changes in blood pH, for example, the need for increased ventilation is rapidly detected. In addition there is evidence that a fall in blood p02 is detectable, since asphyxia (a condition where the blood oxygen content falls significantly, while there is a rise in the pco 2 ) produces a greater influence on ventilation than would be expected from the change in pcc, 2 alone.

The chemoreceptors monitor two fluids in ideal locations-the fluid around the brain stem near the ventilation control centre (see page 19) and the blood, flowing through the carotid arteries (to the head) and the systemic aorta (as the blood leaves the heart).

The fluid around the brain (cerebrospinal fluid or CSF) performs a limited exchange of substances, especially oxygen and carbon dioxide, with the blood supply to vital areas of the brain; monitoring the CSF, therefore, is one possible way to detect significant changes in this supply. Respiratory neurones in the CSF near the brain stem, being highly sensitive to pH and Pcov are quick to detect any change in the 'normal' values; their close proximity to the ventilation control centre in the brain stem makes communication with that part of the brain a simple and rapid step.

The blood flowing in the carotid arteries and systemic aorta is travelling directly to the brain and to all organs of the body except the lungs; thus, sensitive neurones in contact with this supply are ideally situated. In two places the walls of the blood vessels have chemoreceptors embedded in them. These places are called the carotid and aortic bodies and they are sensitive to blood pH, p COz , and p02 . Nerves link them to the ventilation control centre in the brain stem, so that any change in the blood may be very quickly countered by appropriate changes in ventilation, directed by the brain as a result of this detection. (See figure 8.)


internal carotid artery

subclavian artery

innominate artery

superior vena cava

pulmonary artery

inferior vena cava

nerve pathways to medulla

external carotid artery carotid sinus carotid body

common carotid artery

jugular vein

subclavian artery

subclavian vein

nerve pathway to medulla

aortic body

dorsal aorta

. Figure 8The positions of the aortic and carotid bodies in the human circulation. (The pulmonary veins are not shown.)

a Why do you think that there is no direct monitoring of blood pH, Pco2> or Po 2 in tne pulmonary blood vessels?

Nervous control of ventilation

It is in the medulla oblongata of the brain stem that overall control of ventilation seems to be brought about (seefigure 307 on page 427). There


are three major sources of nervous input to this control area: (1) sensory input from the chemoreceptors; (2) sensory input from stretch receptors in the intercostal muscles and in the smooth muscle of the bronchial tree; and (3) input from the cerebral cortex, the area of the brain from which voluntary control over ventilation is exercised. This mixed input ensures that the responses of the control centre are adjusted to meet the ever- changing requirements of the body.

The sensory input is used to operate what can best be seen as a 'switching centre' in the medulla. This centre will, if stimulated, prevent inspiration from occurring, by inhibiting the action of an 'inspiratory control centre'. Sensory input from chemoreceptors prevents the switching centre from stopping inspiration, and the lungs refill with air. This recharging cannot continue indefinitely, and it is essential that some sort of tidal (in and out) breathing occurs. There are nerve pathways that stimulate the switching centre to prevent further inspiration. These nerve pathways carry input from two sources: from stretch receptors which become stimulated as the lung inflates; and from the inspiratory control centre itself as it causes inspiration. A further refinement is the presence of an area in the medulla, the chief function of which appears to be to maintain rhythmic breathing. If the brain of an experimental animal is cut so that the influence of this centre is removed, breathing becomes irregular. The irregularity induced in this way is only noticeable when the animal is anaesthetized; this suggests that higher centres in the brain, notably the cerebral cortex, are heavily implicated in the maintenance of rhythm, and that they commonly override other, reflex pathways.

It appears, therefore, that inspiration can be stimulated auto matically, following input from chemoreceptors, or voluntarily, by the cerebral cortex; whilst inspiration is occurring, impulses pass to a switching centre so that, at an appropriate moment, it may be terminated and expiration may begin.

Expiration is, in humans, almost certainly passive during normal breathing, although it is obvious that you can exhale voluntarily (for example, when you blow up a balloon). Passive expiration is possible because of the elasticity of the lungs themselves and partly because of Man's upright posture. In some mammals expiration may be active because of the possession of a large, heavy rib cage and a horizontal posture, but even in such cases it is likely that the elastic property of lung tissue is of the utmost importance.

The overall picture of the control of ventilation is presented in diagrammatic form in figure 9.

The control of breathing in this way is a good example of an oscillating control system which, because of its dual input (from the stretch receptors in the thorax and the chemoreceptors in the blood and cerebrospinal fluid), needs no external triggers in order to operate continuously. It does, in fact, operate continuously and by so doing it maintains the blood pc02 at a constant level.

It can be seen that a considerable amount of detail is known about the control of breathing; nevertheless there remain many details that are still unclear. It should be remembered that the work really started as long ago as the end of the nineteenth century when the attitude of

Chapter! Breathing and gas exchange in Man 19

arterial blood and CSF chemoreceptors

intercostal muscles and bronchial tree stretch receptors

cerebral cortex voluntary control

feedback from nspiratory control

switching centre (inhibits inspiration

Expiration

Inspiration

Figure 9The control of ventilation.

enquiry shown by Haldane began a chain of investigation that has led to the degree of understanding from which we now benefit. It should also be noted that Haldane's interest was not primarily that of the academic physiologist, but that of a man who wished to understand the practical problems of breathing so that a degree of suffering could be alleviated and so that such activities as mining, which involved breathing under difficult conditions, could be made safer and could be undertaken with less restriction placed upon them by physiological considerations.

Homeostasis

Homeostasis is the term used to describe any system which acts to maintain a steady state. The maintenance of blood carbon dioxide levels is an example of homeostasis because, whether the p c02 of the blood increases or decreases, the system is able to adjust accordingly. The way in which the activity of the ventilation control centre, the partial pressure of carbon dioxide, and ventilation depend upon each other is shown diagrammatically in figure 10.

The state or activity of each part of the system is directly controlled by the activity of the preceding component. Such a relationship is known as feedback, and such systems are commonly encountered in biological studies. They are referred to as homeostatic because they possess the property of maintaining in a steady state at least one of the related quantities. The temperature of the body, blood pressure, the


Pco,

ventilation •»-activity of ventilation

control centre

Figure 10A diagram showing the dependence of ventilation upon the partial pressure of carbon dioxide.

concentration of sugar in the blood, muscle tone, and the pH and pc02 of the blood are all held at fairly steady levels by systems of this kind, and similar examples may be drawn from ecology and genetics. You should note that this is negative feedback-increased activity in one component reduces the activity in the next. This is the normal way in which such systems operate.

Describe one other example of a negative feedback system in operation in biology, and explain briefly how it operates.

Why do you think that there are very few examples of positive feedback systems in biology ? Can you suggest one positive system and explain how it operates ?

Figure 11 is similar to figure 10 and illustrates the logical sequence in the control of pco2 - In this diagram it is assumed for simplicity that the blood pco 2 may be modified from its normal value only by variations in the partial pressure of the gas in inspired air.

Pco.; in inspired air

ventilation control centre comparison difference

desired/normaPCO,

Figure 11A diagram showing the effect of ventilation upon the partial pressure of carbon dioxide.

So far we have assumed that the changes in a homeostatic system take place instantaneously, but this is never true. Suppose that someone walks from an atmosphere containing no carbon dioxide into a room in which the air contains 5 per cent of CO 2 . After inhaling this air there may be an interval of about 0.75 second before the partial pressure of carbon dioxide in the pulmonary vein increases to its new value. There will be a


further delay as this blood passes through the heart and arteries to reach the brain. It will take time for the control centre to modify the subject's ventilation, and still more time before the p co2 of the blood is adjusted by the increased breathing.

The effects of such a time lapse may be shown most clearly by increasing it artificially to an unusual degree. The only simple way to do this is to increase the time taken for the blood to travel from the heart to the brain. In 1956 just such an experiment was performed on a dog. The carotid arteries were lengthened artificially by adding about 9 metres of tubing through which the blood had to flow. The effect of this was to modify the normal pattern of regular breathing into one in which the animal breathed in bursts, with the ventilation reaching a succession of peaks about every six minutes, and midway between those peaks falling to a very low value.

This type of breathing is very similar to a pathological condition known as Cheyne-Stokes breathing. Because of the increased time taken for information about the partial pressure of carbon dioxide in the pulmonary artery to reach the medulla (or, more generally, because of the time required to travel around the circuit shown in figure 11) the action of the control centre is determined not by the current value of pco2 but by its value 2.5 minutes earlier. Under such conditions, when the total time for a message to travel round the feedback pathway of a homeostatic system is long, the system may fail to exert control at a steady state level and instead may cause a kind of oscillation in the fashion described above. Thus one kind of failure, an increase in delay time, may convert a homeostatic system from being beneficial into being harmful. On the other hand there are occasions when such periodicity in the performance of a system is required. One such is the rhythmic performance of the ventilation control centre illustrated in figure 9. It has been suggested that this may well constitute a feedback system of the periodic kind discussed here.

Thus some feedback systems cannot properly be described as homeostatic and we should regard homeostatic systems in general as a special class of stable feedback arrangements. Instability in a feedback system, producing oscillations, may be normal and necessary for proper functioning, or may be pathological and represent a breakdown of some kind in a mechanism which is normally homeostatic.

Coughing, sneezing, and swallowing

From time to time the essential homeostasis of the ventilation control system has to be overridden. The coughing reflex, sneezing, and swallowing are three examples where this is the case.

Figure 12 shows the location of some of the important structures involved in these actions. During ventilation air passes from the trachea to the nasal cavity through the larynx. This structure, a complex of muscle and cartilage, has within it the vocal cords, two tough membranes which can be brought together to intercept or even block the air flow. Normally they are held apart, and the slit-like opening into the trachea which they form is called the glottis. In coughing, sneezing, and

22 Maintenance of the orga

nasal cavity

'ocal cords

lageoesophagus"

Figure 12A section through the human head showing the larynx and associated structures.

swallowing the glottis is obstructed for a time, either by closing the vocal cords (coughing) or by movements of the tongue and epiglottis.

Coughing is stimulated by the irritation of nerve endings in the larynx or trachea, or sometimes deep within the lung itself. Usually, particles of some sort of matter cause the irritation, and coughing serves to remove them. The nerve endings relay impulses to centres within the brain which initiate the cough. The ventilation control centre is overridden and an initial deep inspiration takes place. Then the vocal cords close while the internal intercostal muscles contract. Pressure builds up within the bronchial tree and the vocal cords are suddenly drawn apart, which permits an explosive expiration. It has been reported that air may leave the mo uth with a peak velocity as great as 270 m s ~'.

A sneeze is rather similar in that pressure is allowed to build up in the lungs, following a deep inspiration, before being explosively released. In a sneeze, however, the vocal cords are not usually closed across the glottis. The tongue is used to close the airway through the mouth at first, pressing up against the back of the hard palate, so the expiration passes out mainly via the nasal passage. The tongue then relaxes and some air also passes out through the mouth.

When food is being chewed the hard palate not only serves as a structure against which the tongue can press to squeeze and mould the food bolus, but also keeps the nasal cavity separate from the mouth; and since the soft palate is not being pushed upwards, there is an open airway from the outside to the lungs via the nasal cavity, pharynx, larynx, and


trachea, so that ventilation may continue. When the bolus of food is ready for swallowing, a complex series of events takes place and ensures that no food enters the trachea. The raised back of the tongue pushes the bolus into the pharynx so that it makes contact with the many nerve endings in its dorsal wall, and at the same time pushes the soft palate upwards to close the nasal cavity so that the food cannot pass into it. The excitation of the nerve endings of the pharynx is conveyed to a region of the medulla of the brain which initiates a number of involuntary responses: the vocal cords close and ventilation is immediately inhibited, and the larynx is raised so that its opening is shielded by the base of the tongue and the epiglottis. (Feel your Adam's Apple when you swallow; this is the front part of the larynx.) While all this is going on the bolus is squeezed into the top of the oesophagus by contractions of the muscles in the pharyngeal wall. Once the food is in the oesophagus peristalsis can begin, while the larynx is lowered, the vocal cords open, and ventilation begins again. Of course, choking can occur; it is most common in young children, in whom the development of the musculature to perform these reflex actions is immature, and in old people, in whom the co-ordination of swallowing has become impaired.

2.2 Analysis of human breathing

Practical investigation. Practical guide I, investigation 2A, 'The capacity of the human lungs', and investigation 2B, 'Human consumption of oxygen'.

Investigation 2B demonstrates how oxygen uptake changes in response to exercise, although the measurements in that case may well be made after the exercise has finished. One index of the intensity of activity in humans is to grade it as a multiple of the basal metabolic rate (BMR). BMR is the rate of metabolism of a resting organism as measured by its rate of oxygen consumption. Hence, BMR may be determined by spirometry. That practical investigation will not give a true measure of the BMR of the subject because he or she was seated and awake. A true BMR has to be recorded while the subject is asleep, but a reasonable indication may be obtained by allowing the subject to rest lying down for 30 minutes before the recording is taken; no food should be eaten for at least 12 hours before the recording. Light activity will be found to double the BMR and intense physical exercise may increase the metabolic rate by as much as 10 times.

STUDY ITEM2.21 (Multiple choice)*

Basal metabolic rate in a mammal decreases with an increase in A body size C food intake

D B muscular activity D thyroid activity (J.M.B.)

* In multiple choice items, decide which of the four lettered choices is correct.


It is difficult to measure the oxygen consumption during strenuous physical activity by spirometry, because the subject needs to remain attached to the equipment. It is thus necessary to collect a volume of the expired air for later analysis. One of the most effective ways of doing this is to use a large collecting bag, called the Douglas bag. In figure 13 a subject is running on a treadmill while connected to the bag by a long, flexible hose. A small version of the bag could be strapped to the subject's back so that expired air may even be collected while the subject is moving around or running a race.

Figure 13In the sports science research laboratories of Loughborough University of Technology, Douglas bag techniques are being used to determine the oxygen cost of running. Photograph, Audio Visual Services, Loughborough University of Technology, 1984.

The bag is made of an impermeable material such as flexible plastic. The subject breathes in and out through a two-way valve and the expired air passes into the bag. A nose-clip prevents the subject from breathing through the nasal cavity. After a known length of time the bag is sealed, usually by closing a tap attached to the rubber tubing. The gas is then thoroughly mixed by gently pressing all sides of the bag in turn. The gas content of the expired air may be analysed for carbon dioxide and oxygen content by using simple chemical analysis on a small sample taken from a side tube attached to the bag.


The other important variable in the analysis of human breath is the volume of expired air, VE , usually expressed in dm3 minute ~'. This can be measured by passing the contents of the Douglas bag into a spirometer and measuring the increase in volume of the air chamber, or by simple water displacement. As the composition of inspired air is relatively constant and known, the differences in oxygen and carbon dioxide content of inspired and expired air may easily be calculated. Table 6 shows some typical results.

Inspired Expired Difference VE(%) (%) (dm-'minute-')

carbon dioxide 0 4 4 10 oxygen 21 16.5 4.5 10

Table 6An analysis of air from a Douglas bag.

Ignoring any correction for nitrogen, oxygen uptake may be calculated as follows:

O 2 uptake (K02 ) = (21 - 16.5) % x CO 2 production = (0 + 4) % x 10

10 = 0.45 dm 3 minute' = 0.40 dm 3 minute"

The oxygen uptake, as indicated earlier, may be related to energy expenditure, but these calculations may also be used to determine the respiratory quotient (RQ). Respiratory quotient is the ratio of carbon dioxide produced to oxygen taken up by an organism. In the examplejust given, the RQ would be

0.40045

= 0.89

The RQ is an indicator of the type of food being metabolized during low or moderate intensity work (see table 7). At a high intensity of exercise the RQ (sometimes called the respiratory exchange ratio, or RER, during work) often exceeds 1.00. This indicates that the metabolic activity is partly anaerobic.

Substrate

Carbohydrate

Protein

Fat

Empirical formula

(CH 20)n

e.g. serine C 3 H 7O 3N

e.g. tripalmitate C57 H 110O2

Oxidation

CH 2O + O 2 = CO 2 + H 2O

4C 3H 7 O 3 N + 13O 2 = 12CO 2 + 14H 2 O

2C 57 H I10 O 2 + 167O 2 = 114CO 2 + 110H 2 O

RQ

1/1 = 1.00

12/13 = 0.92*

114/167 = 0.68

* This assumes that all the H and C are fully oxidi/ed in the course of total metabolism and that only the nitrogen is unaccounted for; the N may be assumed to be disposed of via another chemical pathway, in the liver.

Table 7Theoretical values for respiratory quotient, assuming complete aerobic oxidation of the substrate molecules during respiration and complete loss of carbon dioxide through gas exchange at the alveolar surface.


STUDY ITEM2.22 (Multiple choice)

The graph shows the respiratory quotient of germinating sunflower 'seeds'. (Figure 14.) The table indicates the predominant type of

Figure 14(J. M. B.)

12 24 36 48

Time from start of germination (hours)

respiratory activity at the points X, Y, and Z on the graph. Which one of the alternatives A to D gives the correct sequence of activities?

D

A anaerobic respiration aerobic respiration aerobic respirationof fats of carbohydrates

B aerobic respiration anaerobic respiration aerobic respirationof carbohydrates of fats

C aerobic respiration aerobic respiration anaerobic respirationof carbohydrates of fats

D anaerobic respiration aerobic respiration aerobic respirationof carbohydrates offals (J.M.B.)

STUDY ITEM2.23 The use of the Douglas bag

Expired air was collected for 5 minutes in a Douglas bag from a resting subject, breathing fresh air. The mass of the subject was 65 kg. The following data were obtained:

dm3: " ; Total volume of air expired 29.27

Percentage of oxygen in inspired air 20.50 Percentage of oxygen in expired air 15.93 Percentage of carbon dioxide in inspired air 0.04 Percentage of carbon dioxide in expired air 3.98

Use these figures to calculate:

a The subject's V02 (oxygen consumption) in cm3 kg~ 1 minute' '.

b The subject's carbon dioxide output in cm3 kg~ l minute~ l .

D c The subject's respiratory quotient (RQ).


STUDY ITEM2.24 (Essay)

For the following situation, describe the physiological responses of the human body and explain how they are brought about:

In an experimental investigation, a subject with his nose closed by a clipcan only breathe air from and into a gas-tight bag connected to hismouth. The subject breathes and re-breathes air from this bag for a few

D minutes. (J.M.B.)

Maximum oxygen uptake

If oxygen uptake is measured while a subject is performing different types of work, it is possible to determine how the subject is responding to the changing work load by plotting a graph such as figure 15.

_~ 3.0 r

A - weight-lifting at 10 lifts minute

C = cycle ergometer at 70 revolutions minute

Work load (kg m minute )

Figure 15A comparison of work intensity and oxygen uptake for three different kinds of activity. Note that the subjective sensation of work done is related to the oxygen usage and not to the actual work performed.Adapted from Keele, C. A., Neil, £., and Joels, N., Samson Wright's applied physiology, 13th edition, Oxford University Press, 1982.

However, if a subject's work intensity is increased progressively and for a long time, the point will be reached where he becomes exhausted. At this point, or even earlier, the body has reached a peak of oxygen uptake. The subject is simply unable to absorb any more oxygen from the atmosphere, however hard he or she works. The value of knowing a maximum oxygen uptake is that it is the best measure of an individual's endurance potential, and a large maximum uptake is clearly an essential requirement for middle- and long-distance runners. Indeed, every international endurance athlete will have a maximum in excess of


Rest in bedRest, standingWalking, 0.89ms" 1Walking, 1.34ms- 1Walking, 1.79ms" 1Walking, 2.24ms" 1

237328780

106515952543

0.06 dm 3 kg 'minute ' and many in excess of 0.07 dm 3 kg 'minute '. Note that the figures are expressed per kilogram body mass; this is a much more useful measure than dm 3 minute" i since the athlete has to carry his or her body mass during the exercise. This fact also helps to explain why long-distance runners are often of such slight physique.

STUDY ITEM2.25 An analysis of human breath

Douglas and Haldane analysed the air inspired and expired by samples of adult people under different conditions of activity and produced the data shown in table 8.

Condition or activity Oxygen used Carbon dioxide produced at 0°C and 101.3 kl'a at 0°C and 101.3 kPa (cm 3 minute" 1 ) (cm 3 minute"')

197264662992

13982386

Table 8An analysis of human breath during different conditions or activities.From Douglas, C. G. and Haldane, J. S. 'The regulation of normal breathing', J. Physiol.,38, pp.420- 40,1908-9.

The following hypotheses could be made:1 In a resting condition humans use only carbohydrates for respiration.2 As physical activity increases humans derive relatively more energy from carbohydrates than from other sources.3 The mechanism of gaseous exchange in humans can deal with an increase in the production of carbon dioxide more efficiently than it can meet an increased demand for oxygen.4 Increased activity results in an increased use of fat or protein as a respiratory substrate.

a Assess the merit of each hypothesis in the light of the data in table 8 and the information given earlier in this chapter. Accept or reject each hypothesis on the basis of your assessment.

b It is hard to draw certain conclusions from these data because some information is missing. What further data are needed if those in table 8

D are to be useful ?

2.3 The effects of smoking

Lung cancer, heart disease, emphysema, peripheral vascular disease, ulcers, eye and skin disease, and a greater overall susceptibility to infection are all conditions which contribute to premature death; all may be the result of cigarette smoking. Smoking also affects


reproduction and the babies of smokers are smaller than normal and the chances of miscarriage or neonatal mortality are considerably increased. All-in-all, tobacco smoking is the main preventable cause of death in Britain and in most developed countries. In 1982 the Lancet estimated that 95 000 people a year in Britain died prematurely through smoking and the British Medical Journal has estimated that ten million Europeans will die prematurely before the end of the century if people continue to smoke as they do now. In addition it should be remembered that smoking may harm the health of non-smokers who have to live or work with smokers. Considering that the dangers of smoking had been well known for more than 20 years, it was astonishing, in 1984, to find that almost half of the adult population continued to smoke.

Sir Walter Raleigh and others introduced tobacco into Britain in the sixteenth century; it was smoked in pipes and remained for a long time the preserve of the wealthy. At the beginning of the eighteenth century people began taking powdered tobacco as snuff, but it was not until the Crimean War that the British first learned about cigarettes. Factories for the manufacture of cigarettes did not open in Britain until the very end of the nineteenth century. Figure 16 shows the pattern of smoking as it continued from then until 1981. It is quite simple to draw your own conclusions about the trends shown by the lines within that graph.

RCP reports

1 \ I

1890 1900 1910 1920 1930 1940 1950 1960 1970 1980

Year Figure 16The consumption of cigarettes in the United Kingdom between 1890 and 1981. Based on Royal College oj Physicians of London, Health or smoking? Follow-up report of the Royal College of Physicians, Pitman Publishing, 1983.

Appreciating the dangers of smoking

Once large numbers of people were smoking, the stage was set for epidemiologists to discover its dangers. High death rates were first recorded in 1938; in Britain deaths from lung cancer rose from around 0 in 1915 to 170 for every 100000 of the population in 1965. By the mid- 1980s lung cancer in Britain was the commonest terminal cancer among


men, and we have the melancholy distinction of having the highest lung cancer death rate in the World. Studies carried out since 1950 have shown quite unequivocally that:

men with lung cancer are more likely to be smokers than comparable men without the disease;people who smoke are far more likely to develop lung cancer than those who don't.

There is no reasonable doubt about the link between smoking and respiratory disease, lung cancer, and early death. It has sometimes been suggested that those who smoke have some unidentifiable characteristic making them more likely than other people to contract lung cancer and these other conditions, and that smoking is therefore not itself the main cause of these diseases.

a What do you think is the main evidence against this hypothesis?

Smoking since the 1960s

There have been changes in the pattern of smoking since the 1960s, perhaps resulting in part from better understanding of the harmful effects of the habit. Figures 17 and 18 show these changes. Compare the graph for men in figure 17 with figure 18', examine also the histogram in figure 19.

b What do these three graphs suggest about smoking habits and the fall in cigarette smoking?

c Suggest two different reasons to account for the difference between the two curves in figure 18.« 60

50-

40 -

30

20

10

01972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982

YearFigure 17Changes in the prevalence of smoking among British men and among British womenbetween 1972 and 1982.Based on data from the Office of Population Censuses and Surveys.


70

60

s. 50

40

30

20

10A = unskilled labourers

• = professional men

Year1960 1964 1968 1972 1976 1980

Figure 18Changes in the prevalence of cigarette smoking among British professional men and among British unskilled male labourers between 1960 and 1980.

MenNon-smokers

Other CSE or equivalent

No qualification

Women

Degree

Other higher education

A-level orequivalent

0-level or CSE grade one

Other CSE or equivalent

0 10 20 30 40 50 60 70 80 90 100

Percentage of total population Figure 19Cigarette smoking in the United Kingdom, among men and among women, in relation to highest level of qualification. Based on data provided by the General Household Survey.


At the same time as a slight reduction in the amount smoked there have been changes in the cigarettes themselves, partly as a result of government pressures. Most smokers now smoke filter-tipped cigarettes, and the average tar, carbon monoxide, and nicotine yields of cigarettes have fallen markedly, as figure 20 shows.

The effects of tobacco smoke

There are four constituents of tobacco smoke that must concern us here: nicotine, an alkaloid which essentially acts as a nerve stimulant; tars, which vaporize only at high temperatures, and which are irritants to the membranous lining of the bronchial tree; carbon monoxide, which is an asphyxic molecule displacing oxygen from oxyhaemoglobin very readily; and smoke particles, which act as physical irritants when they get into the alveoli.

o o20

•f 10

tar

carbon monoxide

3.0 •?

2.0 o

1.0

1930 1940 1950 1960 1970 1980

Year of manufacture of cigarettes

Figure 20Changes in yields of tar, nicotine, and carbon monoxide in cigarettes sold in the United Kingdom between 1930 and 1982. The graph shows the average yields of each substance obtained from cigarettes with differing yields.Based on Royal College of Physicians of London, Health or smoking? Follow-up report of the Royal College of Physicians, Pitman Publishing, 1983.

Nicotine stimulates at first the parasympathetic nerve endings (see page 340), giving rise to slow heart beat, nausea, or faintness (symptoms of first attempts at smoking); but with use, it stimulates instead the sympathetic endings, resulting in a raised pulse, increased blood pressure, suppressed appetite, and impaired digestion. It is also responsible for causing constriction of some arteries supplying the body surface; forms of arteriosclerosis, including the common atheroma and the rather less common Buerger's disease (which causes gangrene of the feet and necessitates amputation), are probably also exacerbated by nicotine. This substance, like many drugs which act on the nervous system, becomes increasingly ineffective as a nerve stimulant, with repeated doses. So it does not produce either elation or stupefaction for


the smoker. In fact the only satisfaction of smoking is derived from the temporary relief of the deprivation suffered since the last cigarette!

The tars in cigarette smoke produce chronic degenerative changes in the delicate epithelium lining the respiratory tract. Normally the goblet cells in this lining secrete mucus, which entraps particles in the inspired air. The rhythmic beating of surface cilia then moves the particles and mucus, in a kind of mucociliary 'escalator', up towards the trachea where it is coughed up in sputum or swallowed. The tars in the smoke cause the epithelium to secrete increased quantities of mucus, but at the same time inhibit the action of cilia and suppress the cough reflex. (This explains why people who are in the early stages of giving up smoking often cough more.) Since the smoke also contains many more particles than normal air the situation is doubly worsened. The increasing inefficiency of this primary defence system lays the airways open to bacterial infection which further damages the lungs. Bacteria-laden mucus and tar accumulate in the bronchioles and alevoli and alveolar walls begin to break down (emphysema). Such is the accumulation that coughing starts again, leading to the familiar and bronchitic 'smoker's cough'. The smoker eventually becomes quite unable to breathe satisfactorily and rapidly becomes crippled.

Carbon monoxide is now seen as more dangerous than was formerly believed. It is certain that it reduces the blood's efficiency at carrying oxygen and that this, coupled with the reduced ability of the lungs to function properly in gas exchange, makes the smoker in effect slightly anaemic. In heavy smokers carbon monoxide may be implicated in the defective vision sometimes experienced.

Particles over 10 urn in the smoke are normally trapped in mucus and removed by the 'escalator', and larger particles are trapped by the hairs in the nose. Smaller ones, however, penetrate deep into the lungs, and particles below 2 urn will reach the alveoli. There they are ingested by macrophages which have migrated from the alveolar capillaries. The macrophages then move back into the lymphatic vessels with the tissue fluid or are coughed up in the sputum. However, cigarette smoke compromises all stages of the defence and macrophages are less able to engulf these particles; they are also less able to kill bacteria. The action of lymphocytes, which are also concerned with defending the lungs against infection, is also suppressed. Furthermore, the smoke causes the alveolar macrophages to release enzymes such as collagenase and elastase which may help to cause permanent damage to the lung tissues.

Smoking and cancer

The correlation between smoking habits and cancer is quite clear and well-established. Graphs a and b in figure 21 illustrate some of the data about the incidence of lung disease in women.

Express concisely in words the information contained in figure 21 about the effects of the different levels of cigarette consumption.


E o

o o o§ 40

20-

Non-smokers 1-14 15-24 25 +

Smokers: number of cigarettes per day

•- 200r

IoO O O O

150

100

50

Non smokers

Smokers: number of cigarettes per day Figure 21The annual age-standardized death rates from lung diseases in relation to daily consumption of cigarettes, among British women doctors between 1958 and 1980. a Deaths from chronic bronchitis and emphysema.

. b Deaths from lung cancer.Based on Royal College of Physicians of London, Health or smoking? Follow-up report of the Royal College of Physicians, Pitman Publishing, 1983; based on data from Doll, R., Gray, R., Hqfner, B., and Peto, R. 'Mortality in relation to smoking: 22 years' observation in British female doctors'. Br. med. J. 1980: 1: 967-971.

Taking cancer alone, a rather unwelcome picture is given by the data in figure 22 (overleaf).

e Account for the differences between the two graphs.

Two other facts about smoking and cancer are perhaps pertinent:

Very few people who develop lung cancer can be treated and cured. Of 100 people who develop lung cancer, fewer than 5 are alive after 5 years.


400 r

oi 300 Eo o o

§ 200

I 100Q

Men aged 45 to 64 years

•—__^ all cancer

cancer other than lung

lung cancer

400

= 300

I

oo o

100

01 Q

0

1943 1948 1953 1958 1963 1968 1973 1978

Year

Women aged 45 to 64 years

all cancer

cancer other than lung

lung cancer

1943 1948 1953 1958 1963 1968 1973 1978

Year

Figure 22Deaths from cancer in men and women between 1943 and 1978.Based on Royal College of Physicians of London, Health or smoking? Follow-up report of the Royal College of Physicians, Pitman Publishing, 1983.

Smoking also increases the risk of developing cancer of the mouth, throat, oesophagus, bladder, and pancreas.

Smoking and circulatory disease

The link between smoking and coronary artery disease is more complicated than the link between smoking and lung cancer. Coronary artery disease is the commonest cause of death in Britain and in most other developed countries, and the Department of Health estimated that a quarter of the 160000 British deaths from this cause in 1978 were attributable to smoking. The risk of dying from coronary artery disease is two to three times higher in smokers than in non-smokers. But high blood cholesterol, high blood pressure, and many other factors are also associated with coronary artery disease, and the way the risk factors work together is not well understood. In Japan, for instance, where 70 per cent of men smoke, the death rate for coronary artery disease is very much lower than in England and Wales.


Although it is not entirely clear exactly how cigarette smoking contributes to coronary artery disease, the habit seems to encourage the formation of atherosclerotic plaques and the thickening of both the larger and smaller arteries, so obstructing blood flow. In addition, smoking encourages blood clotting in thickened arteries. The high concentration of carbon monoxide (in the form of carboxyhaemoglobin) caused by smoking seems to be the most important factor causing arterial disease, both in heart and legs. The obstruction of the leg arteries leads to pain in the legs on walking and may develop into gangrene. Surgeons can treat obstructed arteries either by bypassing them or by replacing the obstructed portion with a graft. These reconstructive operations are of course much more likely to fail if the patient continues to smoke, and many surgeons are reluctant to operate on patients who will not stop smoking.

Smoking and reproduction

The link between smoking and damage to the reproductive process in females has been established more recently than the first link between smoking and lung disease. Although it is not thoroughly documented, the evidence points towards babies of smoking mothers being smaller and lighter than normal babies. In fact such babies are on average 200 g lighter than the babies of non-smokers. This is a particularly important finding because the risk of a baby dying is related to its mass; the risk of the baby being stillborn or dying in the first week after birth is 35 per cent higher in women who smoke more than 20 cigarettes a day. If a mother stops smoking before the fourth month of pregnancy these risks disappear. That is not to say that smoking early in pregnancy has no effect. Indeed it is suggested that the success rate of implantation of the zygote in the uterine lining may be reduced as a result of smoking, perhaps through a reduced oxygen carriage by the blood of the mother. There are in any case more premature births among smoking women and probably an increased chance of miscarriage. It is becoming apparent that the risks are great and advertising campaigns aimed at pregnant women have been mounted in order to try to bring these facts to their attention.

Smoking and the British economy

Three of the World's largest tobacco companies are based in Britain; between them, in 1983, they had a turnover of more than £10 000 million a year. The British government raised about £3350 million through taxation on tobacco in 1980 to 1981, and at the time of publication about 35 000 people are employed directly by the industry. Many others benefit financially from the marketing of tobacco. On the debit side, about 50 million working days are lost each year through cigarette smoking, and there is a huge financial cost through lost production. Smoking also causes industrial damage: about 20 per cent of all industrial fires are


thought to be started as a result of smoking. Finally the cost to the Health Service of treating smoking-related disease was estimated in 1981 to be more than £160 million a year.

These then are the facts. They pose many questions, not the least among which are 'Why do people smoke?' and 'How can smoking be discouraged?'. The answer to the first question may be partly biological; to the second the answer may be almost entirely social or political. What is unequivocal is that, in one way or another, smoking impinges upon the lives of each of us; this gives us all some obligation to consider its effects.

Summary

1 The partial pressure of a gas in a mixture of gases is a measure of its availability to organisms (2.1).

2 Blood is buffered, so the effect of carbon dioxide entering or leaving the blood may produce very small, although detectable, changes in pH; the rate of ventilation is strongly related to the partial pressure of carbon dioxide in the alveoli (2.1).

3 The restoration of resting levels of carbon dioxide through the co-ordinating activity of the brain is an example of homeostasis (2.1).

4 The medulla oblongata controls ventilation; the system of control operates on the principle of negative feedback (2.1).

5 Reflex control of breathing may be temporarily overridden in order that irritants may be cleared from the air passages or that food may be swallowed (2.1).

6 It is simple to measure the effects of human activity by analysing expired air (2.2).

7 Basal metabolic rate is a measure of metabolic activity and as work increases, so does BMR (2.2).

8 Cigarette smoking has many demonstrably harmful effects on the structure and function of the lungs (2.3).

9 Other functions such as circulation and reproduction also appear to be affected by smoking.

10 Hypotheses about smoking and health should be carefully assessed and judgments should be based upon such critical assessment in the light of the available evidence (2.3).


BEST, c. H. and TAYLOR, N. B. The living body. Chapman & Hall, 1959.(A comprehensive text on human physiology; the terminology seems alittle dated but there is a wealth of detail. Breathing difficulties arediscussed at length.)COMROE, J. H. The lung'. Scientific American. 214(2), 1966. OffprintNo. 1034. (Some detail about ventilation control together with ageneral survey of lung function.)MARSHALL, p. T. and HUGHES, G. M. Physiology of mammals and othervertebrates. 2nd edn. Cambridge University Press, 1980. (Deals fullywith breathing in mammals.)


CHAPTER3 THE CIRCULATORY SYSTEMS OF ANIMALS AND PLANTS

3.1 Movement inside plants and animals

By now you should be well aware that it is vital for the raw materials needed for metabolism to reach all parts of an organism, and for the metabolic waste products to be removed from the cells where they are produced. In small organisms, all of this can be achieved by the diffusion of individual molecules. The larger an organism becomes, however, the less able is diffusion to meet the transport requirements of its tissues. So in nearly all macroscopic organisms some kind of mass flow of molecules is employed. Whereas diffusion involves only the movement of individual molecules or atoms, mass flow occurs when a whole fluid (gas or liquid) moves and all the molecules and atoms within it are transported in the same direction at around the same speed. If the mass flow system becomes totally enclosed within an animal it is called a circulation.

a What are the essential features of a circulating mass flow system?

•'if

Practical investigation. Practical guide 7, investigation 3A, I \ 'Movement inside plant cells'. |

' In plants you can observe quite marked mass flow within individual cells. It is possible to speculate that such movement is concerned with transport of materials in some way, but more evidence is needed to be certain of that. What is more certain is that in large land plants - think of any tree - transport of materials within the organism is vital and must be quite considerable if the needs of all the specialized organs within it are to be met. The roots need a large supply of carbohydrates which are originally synthesized in the leaves; the leaves require a constant supply of water containing mineral ions, which enters the plant from the soil via the roots. At the end of this chapter we shall'investigate the current state of knowledge about the movement of materials in plants; but, when

: concentrating upon animals, we should not lose sight of the fact that equally important and striking physiological mechanisms are required in plants.

3.2 Circulation in animals

Practical investigation. Practical guide /, investigation 3B, 'Circulation in animals'. I

The simplest kind of transport system in animals circulates the external watery medium in which the organism lives, through channels, so that the food and oxygen it contains reach every cell in the body. Such a system is seen in sponges and in certain cnidarians. Most other animals use a body

39

fluid as a transport medium, and this may be a relatively non-specialized, watery fluid circulating in the body cavities (haemocoel or coelom) or it may be a complex tissue circulating in vessels. Some animals, such as nematodes and rotifers, depend upon contractions of the body wall to circulate their body fluid, while in arthropods the blood (haemolymph) is pumped round the haemocoel by a dorsal heart. (See figure 23.)

dorsal diaphragm with alary muscles

gut septa in legs

Figure 23The circulatory system in a generalized insect. The aorta is the main dorsal vesselcarrying blood away from the heart. Although the circulation is open the blood followscertain channels owing to the presence of longitudinal membranes (septa), especially inthe legs.After Wigglesworth, V. B., The principles of insect physiology, 7th edn, Chapman & Hall.1972.

The majority of animals above a certain size have very specialized blood vascular systems for the transport of materials.

It is obvious that tissue requirements will fluctuate: flight from danger demands extra effort from muscles; digestive glands only secrete when food is present in the gut; the activity of excretory organs varies according to the amount of waste produced by muscles and other organs. Circulatory systems must cope with these fluctuating demands by adjusting the supply of blood to the tissues so that it increases with activity and may be reduced to a minimum in inactive tissues. There is far too little blood in an animal to fill every blood vessel simultaneously.

What adaptations would you expect to find in the circulatory system that would enable the distribution of the blood to meet the demands of the tissues?


3.3 Different types of circulation in animals

Open and closed circulations

Practical investigation. Practical guide /, investigation 3C, 'The effect of temperature and chemicals on the rate of heart beat of Daphnia?.

The whole purpose of a blood system is to ensure that the materials it transports can be freely exchanged with cells; heart, valves, and blood vessels are the means of achieving this purpose. The business end, so to speak, of a blood system lies within the tissues where exchanges between blood and cells take place. Circulatory systems are of two kinds, open and closed, which may be distinguished by the fact that they exhibit different relations between blood and the surrounding tissues (figure 24 ).

~blood - at low pressure

"blood vessel

haemocoel filled with blood

" blood - at high pressure

"capillary

"filtration under pressure

—— cell

"absorption of water

——— tissue fluid

Figure 24A diagram of open circulation (left) and closed circulation (right).

In open circulatory systems the cells of the body are actually bathed in blood so that the materials being exchanged simply diffuse through the cell membranes. Open systems are found in arthropods and many molluscs. The dorsally situated heart of an arthropod (see figure 23) pumps blood through the arteries into a haemocoel, a blood-filled space in which lie all the organs of the body. Because of these large spaces blood pressure can never be high in open circulations, and such strict limitations are imposed on efficiency by low blood pressure that this type of circulation is only found in relatively small animals.


Blood in annelids, cephalopod molluscs (for example, squid and octopus), and vertebrates flows in an entirely enclosed system; it never leaves the vessels to come into contact with the tissues. High blood pressure can be developed in closed circulations, with a consequent increase in efficiency.

a Suggest why closed circulatory systems provide a more efficient means of transport than open systems.

STUDY ITEM3.31 Tissue fluid

One of the disadvantages of a closed circulation is that the walls of the blood vessels constitute a barrier between the blood which is trans porting the raw materials required for metabolism and the cells of a tissue, such as muscle, which need those materials. This barrier has to be crossed, and it is at capillary beds within the tissues that this is possible. In different organs and tissues the permeability of capillaries differs because of structural differences in the vessel wall. In muscles, for instance, where there is no requirement for the exchange of relatively

\ large volumes of liquid, the capillary wall is continuous and its permeability quite low.

a In which organs would you expect to find capillary walls that were discontinuous and very permeable ?

You can perhaps see that as the blood enters a capillary bed in an organ at a particular pressure (hydrostatic pressure), this force will be able to move molecules across the capillary walls into the tissues. The magnitude of the force will depend upon the blood pressure at that time in that particular organ, and so it will vary. What we can be sure of is that the hydrostatic pressure at the arterial end of a capillary bed will exceed any opposing forces and hence there will be a tendency for the soluble fraction of blood (plasma) to pass into the spaces within the body tissues. Most cells cannot pass out of capillaries, being too large to get through the capillary walls; many proteins can and do pass through; all other components of plasma pass through easily. The resulting fluid is called the tissue fluid.

Since tissue fluid forms a continuous pathway between the blood in capillaries and the body's cells, and since the walls of capillaries are freely permeable to small solutes such as glucose, ammo acids, and oxygen, these substances diffuse very easily from the blood into the tissue fluid and thence into the cells which may require them. This diffusion depends on there being an appropriate concentration gradient for each molecule.

In opposition to the hydrostatic pressure of the blood there is a difference in water potential between the blood and the tissue fluid (because of the slightly uneven passage of molecules of solute and solvent out of the blood); it results in there being a water potential gradient from the tissue fluid into the blood. This will tend to cause water to move back into the capillaries. So if the values of the hydrostatic pressure of the


blood and the water potential difference between blood and tissue fluid are known for any capillary bed, it is possible to calculate the extent of the filtration out of the blood and the return of fluids back into it.

Figure 25 shows diagrammatically a capillary bed with the artery which supplies it and the vein that drains it.

artery ve

icapillary

HP 4.27 i// -3.33 HP =1.60

I// -0.67 HP negligible

tissue fluid

Figure 25A diagrammatic representation of a capillary bed in a generalized tissue.(HP = hydrostatic pressure; \j/ = water potential; all figures are in kPa.)

There is a hydrostatic pressure of 4.27 kPa in the blood which could result in the formation of tissue fluid at the arterial end of the capillary bed.

Assuming that this is opposed by the water potential difference between the plasma and the tissue fluid, what is the maximum net filtration pressure forming tissue fluid in this capillary ?

How much of the tissue fluid which is formed per unit time will he reabsorbed into the blood at the venous end of the capillary ?

The hydrostatic pressure of blood in different parts of the body is very different. In the glomeruli of the k]dney it may be as high as 9.33 kPa, whereas in the lung capillaries it may be as low as 1.07 kPa.

Can you account for this difference in hydrostatic pressure ? How may it be related to the structure or function of these two organs?

Your calculations will have led you to see that not all of the fluid which is forced out of the capillaries is returned to them. There is a net accumulation of tissue fluid. In Man it has been estimated that around 24dm 3 of tissue fluid are formed each day, of which 22dm 3 are returned to the capillaries at the venous end of the capillary beds.

Can you suggest what happens to the remaining 2 dm 3 of this fluid?

Severe malnutrition is often widespread in tropical countries. It may develop as a result of a diet which is poor in protein as well as in energy- rich foods. Much of the dietary protein is digested and used under these


conditions to provide energy, rather than being assimilated in other ways. The symptoms are many, but one is that the abdomen becomes grossly swollen with an accumulation of fluid.

f Using the information in this section, explain how this symptom of CD malnutrition is produced.

Single and double circulations

The respective arrangements of heart and blood vessels in single and double circulations are illustrated in figure 26. These diagrams merely indicate routes-they tell us nothing about the actual flow of blood.

direction of flow of blood capillaries -

conus arteriosus

sinus venosusatrium veins and sinuses

ventricle

= direction of flow of blood

pulmonary artery

aorta

right atrium

vena cava

right ventricle"

deoxygenated" blood

Figure 26a Single circulation. b Double circulation.


Since poikilothermic vertebrates such as the shark seem to manage quite well with their single circulations you might ask: 'What advantage does a double circulation confer?'. Oxygenated blood from the gills of a fish enters the dorsal aorta at a relatively low pressure (less than 2 kPa) and the amount of oxygen that can be delivered to the tissues by this vessel is limited by this low pressure. Of course it is entirely adequate for the needs of a poikilothermic animal whose metabolic rate is correspondingly low.

Mammals, in common with birds, have a high metabolic rate associated with their ability to maintain body temperature at about the optimum for enzyme activity. A high metabolic rate is only possible if oxygen supplies are also high and this would be quite impossible if the pressure were low in the vessels carrying oxygenated blood to the body.

One method of increasing the rate of oxygen supply would be to use the single type of circulation and raise the blood pressure in it. However, the high hydrostatic pressure would drive fluid through capillary walls and so make the lungs waterlogged. The only successful solution to this problem has been the evolution of a double type of circulation in which blood is pumped to the respiratory surface of lungs at an appropriate pressure which is much lower than that of the aorta. In Man the pressure in the pulmonary artery is about a sixth of that in the aorta.

3.4 Different sorts of heart

Practical investigations. Practical guide 1, investigation 3D, 'The vertebrate heart in action', and investigation 3E, 'The structure of

, hearts'.

If an organism with a muscular body wall contains blood, any contractions of the muscle will tend to move the blood around. However, it will not flow in a particular direction and would be an unsuitable medium in which to transport materials efficiently from place to place within the organism. If the blood is enclosed in a tubular vessel or chamber with valves in it, contraction of muscle in the wall of that vessel will produce directional flow, which is needed if blood is to circulate.

a How do body movements in humans contribute to blood flow?

b How else could blood be caused to flow in one direction in a tubular vessel other than by the use of valves ?

In an insect the heart is little more than a dorsal tube expanded into a series of chambers. It lies within a cavity close to the dorsal wall of the animal. Blood enters it through one-way valves along its length (see figure 23) and is propelled forwards by a series of contractions of the heart (systole), finally being expelled at the anterior end, again through one-way valves. These valves are called ostia. During diastole, which follows systole, a series of alary muscles (one associated with each chamber of the heart) contracts, causing a reduction of pressure within the heart as a result of which it fills.

Chapters The circulatory systems of animals and plants 45

heartbranchial

pericardium ^- vesselposterior aorta

pericardial cavity

abdominal artery

branchial vessel

ventral sinus

sternal artery—-

main haemocoel

water leaves in an anterior direction

Figure 27The open circulation in large crustaceans.a Lobster, b Crayfish.Both are schematic diagrams. Diagram a is a side view and b is a transverse sectionthrough the thorax region.a is after Meglisch, P. A., Invertebrate zoology, 2nd edn, Oxford University Press, 1972;b is after Alexander, R. M., The invertebrates, Cambridge University Press, 1979.

In crustaceans such as the crayfish a little more sophistication is required to allow for the larger size of these animals. In order to get enough oxygen to all the body's tissues a respiratory pigment is incorporated in the blood. This has to be reoxygenated continually if full use is to be made of it. Yet the animal has an open circulation. The problems are overcome by two refinements:

1 the output from the heart is not channelled through just one aorta into the haemocoel, but is sent from the heart through many arteries which serve each organ;2 the heart, though still essentially a tube with ostia, is situated in a cavity called the pericardium into which the heart's contractions draw blood (see figure 27).

In order to enter the pericardium from the haemocoel, the blood has to flow through vessels which pass through the gills where oxygenation can occur. So, by correct positioning of a simple pulsating tube, the driving force for a low-pressure but effective circulation is produced.

In order to produce a higher blood pressure throughout the circulation, a closed system of vessels and a more muscular heart are required. In every heart that you examine from such circulations you will find that there are at least two chambers, one always more muscular than the other.

What important problem has to be overcome for a single-chambered highly muscular heart to work effectively ?

The heart of a fish is very muscular but is in effect little more than a thickened portion of a ventral blood vessel. It is roughly S-shaped and


ventricle = direction of blood flow

Figure 28The two-chambered heart of a fish. After Randall, D. J., 'Fish physiology', Am. Zool. 8,179-189, 1968.

can produce a fairly complex pattern of contraction because of the arrangement of muscles in the walls of its chambers. Apart from the two main pumping chambers - the atrium and ventricle - this heart possesses a chamber before the atrium called the sinus venosus, from where the beat that passes through the heart appears to originate. (Figure 28.)

Mammals have a double circulation. The heart is divided so that there are two atria and two ventricles, which have different amounts of muscle in their walls, allowing the pulmonary and systemic circulations to sustain maximum blood pressures appropriate to their needs.

Suggest how the single circulation of the fish might lead to a lack of circulatory efficiency which the divided heart and double circulation overcome.

The frog's heart shows an interesting intermediate condition between that of the fish and the mammal. Blood entering the heart does so from the lungs (into the left atrium) and from the systemic circulation (into the right atrium via the sinus venosus). However, from the two atria the blood passes into the single ventricle and from there leaves the heart along three pathways-a pulmo-cutaneous pathway to the lungs and skin, a carotid pathway to the head and brain, and a systemic pathway to the rest of the body. (See figure 29.)

e What is the importance of the pathway to the skin in a frog?

f What important problem is presented by the lack of division of a frog ventricle into two separate halves?

conus arteriosus ——

spiral v

sinus venosus

left atrium

Figure 29The frog's heart.

carotid artery systemic arch pulmo-cutaneous arch

pulmonary veins

anterior vena cava

atrio-ventricular valves

ventricle


Figure 30(Parts a to h of figure 30: J. M. B.)

direction of drum rotation

AAM1 2 3 4 5 '6 7

Time (s)

i pivot

Time (s)

Sinus venosus stimulated

STUDY ITEM3.41 (Short answer question)

A series of experiments was performed to investigate the action and physiology of a frog's heart. The heart of a pithed frog was exposed as fully as necessary and attached via a small clip and thread to a pivoted lever and pen. Movements of the lever produced by contraction of the heart muscles were recorded on the rotating drum of a kymograph. Figure 30a shows a recorded trace of the beating heart.

a How fast was the kymograph paper moving ?

Figure 30b shows an enlarged part of the trace in figure 30a.

b 1 Describe, very briefly, the action of the heart which corresponds to each of the portions of the trace marked A, B, C, and D. 2 From the appearance of the trace, decide where the thread from the heart was attached to the lever. Copy the unfinished illustration of the kymograph lever and pen, and complete it by drawing in the position of the thread that attaches the heart to the lever. Briefly explain your answer. (Figure 30c.)

Ringer's solution, heated to 30 °C, was poured over the whole heart at the time marked 'X' and the effect on the heart was recorded (figure 30d).

c From the trace, determine the maximum effect of raising thetemperature of the whole heart to 30°C on (1) the rate and (2) the amplitude of the heart beat.

A metal rod was then warmed in the Ringer's solution to 30 °C and gently pressed against the sinus venosus, atria, and ventricle in turn. The heart was allowed to regain its normal beat and the rod was reheated between each operation. Figures 30e to g show the results.

Atria stimulated

Ventricle stimulated

AW1M A-vUWTime (s) Time (s) Time (s)

AMStimulation of the vagus nerve

i

Time (s)I i

eD

What do the traces shown in figures 30e to g suggest about the control of the contraction of the heart?

After a further period of normal heart contractions, the cardiac branch of the vagus nerve was stimulated by repetitive electrical pulses.

Copy and continue the trace in figure 30h to show the expected result of stimulating the vagus nerve. (J.M.B.)


The mammalian heart in action

You should have some idea of what the mammalian heart achieves when it beats and how it operates as a part of the complex double circulatory system. This section attempts to integrate your knowledge with more detailed physiological information and so build up your understanding of how the heart functions.

Cardiac muscle

Practical investigation. Practical guide 1, investigation 3j£, 'The vertebrate heart in action.'

The heart is largely composed of short, striped muscle fibres which are joined together at their ends, and also by lateral bridges. Because of these junctions the tissue is in the form of a continuous network adapting it for the conduction of excitation waves from fibre to fibre (figure 31). By acting together as a sheet of tissue the individual fibres produce a more powerful effort when they contract simultaneously. Between the fibres are spaces occupied by blood vessels and connective tissues.

——— blood cells

bridges\ .-> n, ,/.. /' ("j -j~•"— nucleus centrally

' ' placed

——• ^connective tissue fibres

— intercalated discs

—— myofibrils

cardiac muscle — ~[ fibres

mm \m'mmT—striations

Figure 31A diagram of a longitudinal section of cardiac muscle.

Muscle tissue does a lot of work and needs a good blood supply; cardiac muscle receives oxygenated blood from the base of the aorta via two coronary arteries. Deoxygenated blood is collected from the capillaries by coronary veins and returned to the right atrium through the coronary sinus. The arrangement of the blood vessels of the heart is shown in figure 32.


aorta

coronary arteries

- left ventricle

right ventricle

right atrium

coronary veins

coronary sinus

Figure 32A diagram of the blood vessels of the heart.

Whenever muscle tissue of any kind relaxes after it has contracted it has to be stretched before it is in a state of readiness for the next .contraction. The skeletal muscles are arranged in antagonistic pairs, such as the biceps and triceps muscles of the arm. A contracted muscle gets stretched by the contraction of its antagonist.

There are no antagonists in the heart to stretch its relaxed muscle fibres and the problem is solved in a different way by elastic recoil. Muscular contraction deforms the connective tissue fibres and immediately relaxation of the muscle begins, these distorted fibres tend to return to their previous condition, thereby providing a recoil mechanism that automatically stretches the muscle fibres. Heart muscle can be stretched even more vigorously by the dilatation of the heart with blood, a condition that can also be induced experimentally. This idea was first formulated by E. H. Starling in f 914 and has become known as Starling's Law. He realized that the force of contraction of the ventricle is proportional to the degree of stretch of the muscle fibres during filling: an elegant additional feature for a pump of variable output. In common with skeletal striped muscle, cardiac muscle has an abundance of mitochondria; their presence can be correlated with the great activity of these tissues, since processes concerned with the transfer of energy occur within mitochondria. (See page 152.)

If any muscle tissue is stimulated to contract by the application of a suitable electrical stimulus, it cannot be excited to contract again until after a brief interval. This period of complete inexcitability is the absolute refractory period; it is followed by a relative refractory period during which the tissue can be excited, but only by relatively strong stimuli. Contraction and relaxation also last for definite periods of time and these differ according to the kind of muscle. (See page 348.) Cardiac muscle has a


long refractory period lasting almost as long as the periods of contraction and relaxation, which means that no two successive contractions can be merged (figure 33 ). Contrast this with skeletal muscle, where the ability to merge contractions is used to produce sustained muscular effort.

absolute relative refractory period refractory period

time

normalexcitability

i!V. — — — — _

notexcitable

i ,'

/

only excitedby largestimuli

heightenedexcitability

normalexcitability

= contraction

— — — = excitability

Figure 33The refractory period of cardiac muscle.

There must always be a rest period between successive contractions which are quite distinct from each other. Heart tissue thus beats in a rhythmic fashion. The rest period is of great importance in heart beat since it provides a safety device protecting the heart from fatigue; no organ liable to fatigue could go on working non-stop, as the heart does.

The job of the heart is to pump out jets of blood under pressure, for which it is admirably adapted by the rhythmic nature of its beating. Blood is expelled from the ventricle by a wringing type of action and in this connection there is a nice structural adaptation in the arrangement of the muscle fibres in spiral groups. There are four groups of muscle fibres. Two of these are oppositely wound spirals encircling both ventricles; the third group also folds round both chambers and is situated under the first two; while the fourth group surrounds the left ventricle only (figure 34).

The left chamber has to pump blood to all parts of the body and its walls are five times as thick as those of the right ventricle, which only pumps blood to the lungs. The four spiral groups of muscle fibres enable the heart to wring out blood very much as water might be wrung out of a damp cloth.

Figure 34The arrangement of the four groups of muscle in the ventricle.


STUDY ITEM3.51 The action of the heart

a Which of the following is most likely to cause the heart sounds heard through a stethoscope ? A Contraction of the ventricles B Filling of the ventricles C Closure of the heart valves D Contraction of the atria and ventricles.

b Give a reason for your choice.

c Explain briefly how the intermittent action of the mammalian heart is D converted into a steady flow of blood.

The origin of heart beat

Cortes, the conqueror of Mexico in 1519, was horrified by the custom of the Aztecs who sought to propitiate their Rain God by human sacrifice. This was done by swiftly removing a victim's heart with an obsidian knife and holding the excised organ aloft for the Rain God's approval. The ghastly offering was only considered acceptable if it was still beating.

Turning to less gruesome examples, the heart of a chick embryo beats long before the developing nerve fibres have reached it. When a freshly killed frog is dissected, it is a common experience to observe the heart beating and these rhythmic contractions persist even if the heart is removed from the animal. Ringer (1883) quite by accident discovered that he could keep an isolated frog's heart beating for a much longer time if he perfused it with a solution carefully balanced for salt content, in particular, sodium, potassium, and calcium ions. This chance discovery is now part of everyday biology usage, since we refer to an artificial solution with the same salt composition as plasma, as Ringer's solution. In 1890 Martin succeeded in keeping a mammal's heart beating for some time by perfusing it with mammalian Ringer's solution at body temperature.

All the examples considered above involve a heart beating when deprived of nerve connections; the origin of heart rhythm cannot be neurogenic (due to the influence of nerves) but must be an inherent property of the heart muscle itself. That is, it is myogenic, meaning arising within muscle. A simple experiment to investigate the myogenic origin of heart beat in the frog is to tie what is known as a first Stannius ligature between the sinus venosus and the atria of a freshly killed frog. When the ligature is tightened, the atria and the ventricle stop beating but the sinus venosus continues to beat with its original rhythm. Usually, after a lapse of time, the atria or the ventricle does start beating again but with an entirely new rhythm which never coincides with the original one it had before the ligature was tied. The results of this experiment support the myogenic hypothesis and point to the sinus venosus as the site of origin of the excitation wave in a frog's heart.

Although birds and mammals lack a sinus venosus it is present in their embryos. The sinus venosus of the embryo becomes reduced to a


patch of tissue in the adult which was discovered in 1907 by Keith and Fleck. Such a small degenerate organ is called a vestige. In birds and mammals the vestigial sinus venosus, known as the sino-atrial node, is situated just below the opening of the superior vena cava into the right atrium. Evidence that this node is the site of the origin of the excitation wave in birds and mammals is derived from experiments in which the rate of heart beat is changed by heating or cooling the node. Further evidence is provided if recording electrodes are inserted into the heart; the electrical changes which always accompany muscle contraction are first detected in any one cycle of events in the sino-atrial node.

There now seems little doubt that the sinus venosus in fish, amphibia, and reptiles and the sino-atrial node in birds and mammals act as pacemakers from which originate the successive waves of excitation that determine the rhythm of heart beat.

Conduction of the excitation wave

Muscle tissue serves as a conducting channel in the atria of mammalian hearts; the excitation wave spreads from the sino-atrial node to both atria in the muscle fibres, eventually arriving at the base of the right atrium. Here there is a second node, the atrio-ventricular node, first described by Tawara in 1906. A bundle of exceptionally large muscle fibres arises from the atrio-ventricular node (figure 35). These are the Purkinje fibres, named after the great Bohemian scientist who first observed them. In sections of cardiac muscle that have been stained with periodic acid, Scruffs reagent (PAS), Purkinje fibres appear purple as a result of the glycogen they contain reacting with the stain.

The bundle of Purkinje fibres (called the bundle of His) arising from the node forks into right and left branches which pass into the respective ventricles where fibres can be traced to all parts. Although these fibres are muscle fibres they share with nerves the property of conduction and are used to conduct the waves of excitation from the atrio-ventricular node to the muscle of the ventricles. Evidence for this is obtained by experimental clamping of the right or left bundles. When the left bundle is clamped its fibres are squashed and unable to conduct; under these conditions the left ventricle stops beating but'the right continues to do so. Exactly the reverse happens when the right bundle is clamped.

The sequence of events in the origin and conduction of one excitation wave in the mammalian heart is as follows:

1 The wave originates in the pacemaker, the sino-atrial node, and is conducted from there via atrial muscle; the fibres of the muscle contract as the wave reaches them. The wave reaches the atrio-ventricular node 0.045 second from the time of origin.2 A time delay occurs at the atrio-ventricular node and 0.12 second elapses before the wave passes on. This delay prevents the overlap of atrial and ventricular contractions.3 Purkinje fibres conduct the wave from the atrio-ventricular node in the muscle either side of the septum and, again, the muscle fibres contract as the wave reaches them.


4 The wave reaches the base of the ventricles 0.04 second after leaving the atrio-ventricular node and then spreads up the lateral walls to reach the top of the ventricles 0.08 second after leaving the node.5 The whole sequence of events takes 0.245 second. (See figure 35.)

superior vena cava

sino-atrial node (pacemaker)

right atrium inferior vena cava"""""

0.045 second —-

0.165 second————h

septum

pulmonary veins

excitation wave

atrio-ventricularnode0.245 second

Purkinje fibres

0.205 second

Figure 35A diagram of the mammalian heart showing the origin and direction of the excitation

STUDY ITEM3.52 The cardiac cycle

Each chamber of the heart contracts as the excitation wave reaches it; a phase of contraction is referred to as systole. After they have contracted, the muscle fibres relax; the phase in which a chamber is in the relaxed condition is known as diastole. Because of the site of origin and the manner in which the wave is conducted atrial systole always precedes ventricular systole. There is a cycle of events associated with systole and diastole; the events that occur between, say, one atrial systole and the next is known as the cardiac cycle.

Figure 36 shows the main changes in pressure that occur in the heart during the cardiac cycle. Study it and then answer the following questions.

a During which of the numbered phases of the heat, 1 to 5, would you expect each of the following events to occur?1 Rapid filling of the ventricles.2 Increase in tension in the ventricle muscle fibres without any change in their length.

b What might account for the rise in pressure in the aorta during phase 1?

c If the rate of heart beat is to increase during exercise, one or more parts of the cardiac cycle must take less time. Which of the five phases could be shortened with least influence on the effectiveness of the heart beat?


diastole systole diastole

diastole systole diastole

phases in the cardiac cycle

34 5 1

- 140

- 120

- 100

-,160 -

56789

Time (tenths of a second)

- ventricle

— — — = atrium

• — • — • = aorta

Figure 36Pressure changes in the heart during the cardiac cycle.Based on figures from Best, C. H. and Taylor, N. B., The physiological basis of medical practice, 4th edition, Williams & Wilkins Co., 1945; and Hogg, M. E., A biology of Man, Heinemann, 1966.

Electrocardiograms (ECGs)

Resting muscle cells show polarity - the inside of the cell is about 70 to 90 millivolts negative with respect to the outside. Immediately before contraction this polarity reverses and the inside becomes 30 millivolts positive with respect to the outside. The body acts as a conductor and these changes in polarity, known as action potentials (see page 333), can be detected by electrodes placed on the skin provided that a sufficiently sensitive instrument is available. Modern instruments employ a very sensitive galvanometer and a pen recorder, or a cathode ray oscilloscope. The records of the action potentials of heart muscle form an electrocardiogram, or ECG (seefigure 3 7 ). The ECG shows characteristic deflections or waves, and each wave, designated by the letters P, Q, R, S, or T, corresponds to the depolarization preceding a phase of contraction or to the phase during which polarity is recovered. The P wave follows the firing of the sino-atrial node and corresponds with the depolarization that precedes atrial systole. The QRS complex is the depolarization preceding


ventricular systole, and the T wave marks the period of recovery of the ventricles during which they regain their lost polarity. Any irregularity in cardiac muscle function will show up as a change in the ECG, so these records provide the doctor with invaluable information about the functioning of a patient's heart.

P corresponds with the spread of the excitation wave over the atria. This positive deflection precedes atrial systole.-

QRS conduction of excitation wave by nodes and Purkinje fibres. Q and S are negative.

R a tall positive spikepreceding ventricular systole

T positive deflection which accompanies the relaxation of the ventricles.

Figure 37a A diagram of an electrocardiogram.b Electrocardiogram traces of a normal adult.b is from the Department of Cardiology, Charing Cross Hospital Medical School.

Catheterization of the heart

Heart output can be calculated by a variety of indirect means. In one technique, blood is withdrawn from the pulmonary artery by a catheter, (see figure 38).

The output of the heart in a man under conditions of complete rest is found to be between 4dm3 and 5dm3 per minute; this amount varies with surface area. It increases by 2 dm3 per minute after a meal and rises to 20 dm 3 per minute during exercise. An athlete, by training, can raise this figure to 30dm3 per minute or more.

Before operating to correct or replace diseased or damaged atrio- ventricular valves, the surgeon may use the catheter to investigate their condition, since reduction in the output of a heart gives a very accurate measure of the degree of restriction of the faulty valves.


right atrium

pulmonary artery

catheter

right ventricle

syringe for withdrawing blood sample

Figure 38A diagram showing the catheter in place, when blood is to be withdrawn from the pulmonary artery.

3.6 Heart surgery and the heart-lung machine

If the heart begins to fail to pump sufficient blood, its owner will gradually become ill and unable to undertake normal activities. If the heart stops suddenly, death follows within minutes. After only a minute or two the brain loses the ability to function at a high level and consciousness is lost; after another minute or two more basic brain functions, including breathing, fail. This will be followed in quick succession by the failure of the liver and then the kidneys. By this time, a mere five or six minutes after the heart stopped, if the patient were resuscitated and the heart re-started, the brain would never again function normally. The same sequence of events takes place if a surgeon stops the heart in an attempt to repair damage caused by disease; unless, that is, some attempt is made to maintain the functions and the circulation of the blood without it.

Heart disease

The heart is capable of pumping up to 10 tonnes of blood daily and it beats 40 million times each year. It is surprising that it does not fail more often. Yet the heart is immensely reliable, when it is not damaged by Man's harmful habits, such as incorrect diet, lack of exercise, and smoking. In addition, a heart is sometimes defective from birth. The severity of the defects with which people are born ranges from almost insignificant abnormalities which may never cause illness to those which need surgery soon after birth if the child is to survive.

During the development of the heart a large number of changes take place over the space of a few days about three weeks after conception. If this sequence of events is interrupted parts of the heart may be incomplete or deformed, creating holes between the two sides of the


heart or making leaky valves. At birth also, there are modifications that have to be made to the heart and to the main aorta and pulmonary artery which, if they fail to occur, will leave the child with an imbalanced circulation and a heart that is not functioning correctly. This may damage the heart and lungs irreversibly and may lead to early death if it is not quickly corrected. These changes are discussed in greater detail in the next chapter, in section 4.2.

Half of us will go on to acquire disease of our heart and blood vessels, and most of this disease is self-inflicted and entirely avoidable. One quarter of all the people in the Western world die unnecessarily young, from blockage of the coronary arteries which causes death from a heart attack (also known as a coronary or coronary thrombosis). The same disease process blocking an artery in the brain causes a stroke. The coronary arteries supply the heart muscle with blood and are therefore absolutely vital to its continued functioning. They have only about the diameter of a drinking straw and they are the first branches of the aorta, leaving it very near to the top of the atria and curving back straight into the cardiac muscle. The disease which blocks them is known as atheroma or arteriosclerosis, and is almost certainly avoidable. It relates to our life style and, for example, people who smoke are far more likely to die or be crippled by atheroma than are non-smokers. (See page 37.)

Operations on the heart

Life has to be maintained while the heart is repaired. Several methods were in use before the heart-lung machine. One successful method was to cool the patient to 30 °C in a bath of ice-cold water. At this temperature the surgeon could shut off the circulation for up to four minutes, which was just long enough to close simple holes in the heart septum or valves. Operations on the valves were done as a matter of routine by feel, with the fingers and instruments pushed into the chambers of the heart. Obviously there were many, more serious conditions that could not be remedied in this way and in such a short time, so there was a great stimulus for the development of techniques which would prolong the time during which a heart could be operated upon.

The first steps towards the routine use of the heart-lung machine involved the use of two pumps. One took blood from the venae cavae and pumped it to the lungs for oxygenation (bypassing the right side of the heart), while the other took blood from the pulmonary vein and pumped it into the aorta (bypassing the left side of the heart). This blood was cooled as low as 8 °C before being pumped into the aorta; as a result it cooled the organs through which it passed. Once the brain, liver and all the vital organs were cooled sufficiently to stop their activity, blood was drained from the patient and about one hour was available for operative work on the heart. The whole process, including cooling and rewarming, often took all day or longer, and the results were poor and the costs high.


The heart-lung machine

When factory-produced, disposable gas exchangers (known as oxygenators) became available, circulation of the blood outside the body became commonplace. Now nearly one-third of a million patients undergo open heart surgery every year in Britain. There are small variations in design and technique but the description that follows is typical. As you read it, consider two things-the complexity of the engineering and chemistry that have to be employed to come anywhere near to simulating the body's own systems and mechanisms; and the fact that inevitably these expensive and complex efforts meet only very limited success and incorporate a degree of danger and a chance of failure.

Figure 39An operating theatre being prepared for heart surgery. Photograph, Dr R. H. Klipstein, National Heart Hospital, London.

Circulating the bloodBlood is withdrawn from an adult patient via a 12-mm polyvinylchloride(PVC) tube draining the superior and inferior venae cavae, the main


veins which return blood from the body to the heart. The blood passes by gravity to the oxygenator which contains a heat exchanger. The oxygenator adds oxygen to the blood and lets carbon dioxide escape, after which the blood is passed to a pump where the pressure is raised enough to force the blood through an 8-mm PVC tube into the aorta after filtering, if so desired.

Most of the tubing used in heart-lung machines is made of PVC which, in comparison with the real blood vessels, is an unsuitable material consisting of hard granules with fillers and plasticizers between them; the surface is very rough and so causes damage to the blood. PVC melts too easily to be sterilized by heat so this is done before the operation, by toxic epoxyethane gas, which is very hard to remove. In contrast natural blood vessels are very smooth and flexible; their walls are constantly being repaired and they secrete a prostaglandin (see Study guide II, Chapter 24) called prostacyclin (PG f 2) in minute quantities; its function is to prevent platelets from adhering to the vessel walls and thus to prevent clot formation. None of these refinements is present in PVC tubing (see figure 40).

Figure 40In the heart-lung machine, pressure and the surface qualities of the pump tubing play an important part in blood damage. Here, four materials which appear to be smooth are compared with red blood cells. The upper pair of tracings (PVC) is to a different scale from the lower pair (electropolished stainless steel and silicone rubber plastic); in each, a red cell is drawn to the same vertical scale; the horizontal scale is compressed 20 times (upper pair) and 100 times (lower pair). On each scale a natural blood vessel would show an almost perfect straight line. In addition to these microscopic abnormalities, badly extruded tubing contains memory lines from the imperfectly blended plastic granules. From Longmore, D., Spare-part surgery, Aldus, 1968.


The blood pumps used, although carefully designed to the strictest specifications, are able to cause damage to the blood and problems in the circulation. Most blood pumps consist of a semi-circular housing 127mm in diameter, which contains a loop of silicone rubber tubing 12mm in diameter. A rotating arm with a roller at each end turns at speeds of up to 120 revolutions per minute. (See figure 41.) The pump head must be strong and well engineered; if the roller presses too hard on the tube, blood cells will be crushed and pieces of the tube will be torn off and will pass into the patient. Worse, if the pump is not set tightly enough, blood will leak back across the narrow gap, creating an area in which the pressure is so low that the gases dissolved in the blood come out of solution and pass into the patient as a stream of bubbles.

Figure 41A close-up of the basic unit of the blood pump for cardiopulmonary bypass. This shows the roller device which spins, massaging the tube placed in it to propel blood around the tubing and the patient's circulation. Dr R. H. Klipstein, National Heart Hospital.

Oxygenators and heat exchangersTwo kinds of oxygenators are in common use.

Membrane oxygenators are the safest, the most expensive, and the most inconvenient! The blood is passed over a thin membrane which is made of silicone rubber or microporous Teflon (both permeable to gases) and oxygen is passed over the other side of the membrane. The designers try to make the membrane as thin as possible to simulate the lung surface. Although the area of exchange comes nowhere near that of the human lung, they work quite well.

Bubble oxygenators make a froth by bubbling a suitable mixture of gases through a column of the blood. The blood then has the bubbles


removed by being passed over a silicone antifoam agent bonded to a plastic sponge. Invariably some bubbles and some antifoam escape into the patient and inevitably cause damage though it may be slight.

Most oxygenators incorporate a number of parallel tubes or a metal coil through which water can be passed at a controlled temperature. Most surgeons find it helpful to augment the natural cooling that occurs when the patient's chest is open and the blood is circulating outside the body, by using the heat exchanger to cool the patient actively to around 30 °C. If there were a mechanical failure or a blown connection at this temperature the patient would be safe for a few minutes, allowing time for repairs. Extreme care is required during rewarming, for if the temperature of the surface of the heat exchanger exceeds 42 °C, blood proteins will be denatured.

Keeping the blood liquidIn 1935 an extract of liver which prevented blood from solidifying was discovered and named heparin. The addition of sufficient heparin keeps the blood liquid for a long time and little obvious clotting takes place. In reality, though, the clotting process does start and many of the essential ingredients are consumed. Thus, even with the use of heparin, by the end of the operation the blood clotting mechanism is mostly exhausted and many patients bleed. Heparin does not in any way inhibit the blood platelets whose function is to plug small breaches in the vessel wall and to initiate the chemical clotting mechanism, and during an operation large numbers of clumps of aggregated platelets pass into the patient.

The prostaglandin PG12 mentioned earlier, which inhibits the blood platelets and stops the clotting mechanism in humans, was discovered by John Vane and his colleagues in 1977. The addition of minute quantities of PG12 to the circulation outside the body preserves platelets, prevents post-operative bleeding, and dramatically improves the patient's general wellbeing after open-heart surgery. Figure 42 gives an idea of the effect of this substance.

Filtering the bloodAfter reading the preceding paragraphs you will not be surprised to learn that many surgeons use a filter in the arterial line to the patient in order to remove bubbles, plastic flakes, platelet aggregates, and other foreign material from the blood. Not all surgeons employ filters because it is hard to design an effective one that does not also damage the blood. A red cell is about 7 micrometres in diameter and white cells are between 8 and 16 micrometres; a filter with a pore size of less than 22 micrometres damages both types of cells. In addition some surgeons are convinced that such filters may actually cause platelet aggregation.

Monitoring and the control of the heart-lung machine During open-heart surgery the patient is anaesthetized and paralysed and the heart is stopped. There are none of the normal signs of life which the anaesthetist and surgeon can use to assess the state of the patient. Indirect methods have to be employed. The revolutions of the arterial pump are monitored and this and the diameter of the tube will indicate the amount of blood circulating in the patient; the pressure in the arterial


Figure 42The photographs show scanning electronmicrographs of blood filters that have beenused to filter blood circulating outside the body. The same volume of blood has passedthrough both, and in each case it was adequately treated with heparin to preventclotting.In photograph a (x 1 300000), the prostaglandin PG12 has also been added to theblood. A few platelets may be seen adhering to the strands of the filter material.In b (x 1700 000), no PG12 has been used. Platelets have adhered to the filter and manyhave broken up, starting the clotting reaction. Strands of fibrin can be seen clearly.Photograph, Donald Longmore, National Heart Hospital, London.

line and in an artery in the patient indicate whether the output from the pump is adequate and warn of any obstruction to flow; the temperature of the water in the heat exchanger, the blood, and the nose (reflecting brain temperature) are also monitored. Normally the acid-base balance of the body is coarsely adjusted by the kidneys which excrete acid in one form or another, and finely adjusted by the regulation of breathing which controls the concentration of carbon dioxide in the blood. It is vital that the overall acid-base balance is maintained; therefore, during the operation, the urine output is measured and the dissolved oxygen and carbon dioxide are determined every fifteen minutes. Adjustments are made by altering the gases entering the oxygenator.

Chapter3 The circulatory systems of animals and plants 63

The future

There is no doubt that the heart-lung machine has enabled quite complex open-heart surgery to be undertaken relatively safely and that lives have as a result been prolonged. Replacement of a heart valve is fairly common and bypassing a coronary artery almost routine. But within a few years it should be possible to go one better than all of this and prevent the vast amount of acquired disease which affects the heart. As people come to understand how to live so that they avoid factors that cause it, the number requiring heart operations will fall. At the same time, a wider appreciation of the shortcomings of the present apparatus and techniques will result in better designed machines made from more suitable materials, particularly materials not requiring dangerous epoxyethane sterilization.

3.7 The nature of blood vessels

Practical investigation. Practical gu ide 1, investigation 3F, 'Arteries, I veins, and capillaries'. i

Already in this chapter you have been asked to suggest means by which intermittent heart output is converted into continuous blood flow. A more thorough examination of the vessels in which blood is flowing will allow you to do this with more certainty. This section examines the structure of the main components of the circulatory system.

The aorta

This great artery has very thick walls which are composed of smooth muscle, connective tissue, nerve fibres, and an inner lining, the endothelium. The thickness of the walls is an adaptation to withstand the high blood pressure to which the vessel is subjected. Figure 43a shows a section of the aorta wall, under low magnification, in which the tissue has been stained to show elastic fibres. The bulk of the wall (the tunica media) is composed of sheets of elastin interspersed with collagen and relatively few smooth muscle fibres (figure 43b). The collagenous tunica adventitia contains small blood vessels-the vasa vasorum.

a What function do you think is served by the vasa vasorum ?

With increasing age the arterial system becomes less elastic.

b What signs might be looked for in an elderly patient as a result of this change?

Arteries

Arteries branch off the aorta. At first their walls are similar to those of the aorta-these are the elastic or conducting arteries. Blood passes from them into distributing arteries, which branch to supply different organs


Figure 43Part of a transverse section through the wall of an aorta.In figure a, x 52, the lumen of the aorta is on the left of the picture. In both figures theelastic fibres are specifically stained as black lines. Note the three basic layers in the wall:the tunica intima (I), the tunica media (M), and the tunica adventitia (A).Figure b shows a portion of the tunica media at greater magnification ( x 840).From Wheater, P. R., Burkitt, H. G., and Daniels, V. G., Functional histology-a text andcolour atlas, Churchill Livingstone, 1979.


with blood. All these arteries have thick walls and relatively narrow lumens. Figure 44 shows a transverse section through a distributing artery.

In what major way does the wall of this vessel differ from that of an elastic artery such as the aorta ?

tunica media

Figure 44A transverse section through part of the wall of a distributing artery ( x 59). This section has been stained in the same way as those in figure 43. Photograph, Biophoto Associates.

Arterioles

Within the organs the distributing arteries divide into smaller and smaller arteries and eventually into arterioles. There is no sudden transition from one type of vessel to another; large arterioles are very similar in structure to the small arteries; small arterioles can be distinguished by the smooth muscle fibres wound around their walls in a spiral fashion.

Capillaries

Blood from arterioles flows into 'thoroughfare channels' whose walls are very thin with sparsely distributed muscle fibres. Capillaries arise from these channels, each capillary having at its point of origin a ring of smooth muscle, the pre-capillary sphincter. (See figure 45.) Capillaries are the business part of the circulation and the blood flow through them is variable. Some of the more familiar changes in capillary flow occur in the skin. Hot weather, exercise and sometimes emotional embarrass ment cause a flushing of the skin; this redness is a sign that the capillaries are dilated. In cold weather the capillary circulation is restricted, and inactive tissues may have little or no blood in their capillaries. The


velocity of flow through a capillary is very slow indeed but, because there are so many of them, the heart can pump all the blood through them in a matter of minutes. Many tiny streams flowing into a river can produce a substantial torrent; so it is with blood, which trickles through the capillaries at a velocity of a mere 0.5 mm per second in each capillary. The same blood rushes through veins at over 300 mm per second.

pre-capillary sphincter

'thoroughfare channel'

'shunt' vesse

capillaries

arteriole ~

Figure 45A schematic diagram of a capillary bed, illustrating the position of pre-capillary sphincters.

d How do you think that1 the muscles in the arteriole walls and2 the pre-capillary sphincters assist in controlling blood flow?

Venules

The transition from a capillary to a venule is rather gradual and a venule is identified by the first appearance of smooth muscle fibres in the wall of a vessel. Blood is drained from the capillary beds by thin-walled venules which unite to form small veins.

Veins

Blood eventually gets back to the right atrium of the heart through the inferior and superior venae cavae. The larger veins open into the venae cavae and themselves receive blood from the smaller veins draining the organs. In veins from the extremities of the body, backflow is prevented by pocket valves in the walls; these are absent from the veins of the thorax.

Why do you think that valves are unnecessary in the veins of the thorax?


The flow of blood through vessels

Surface area and resistance to flowThe application of hydrostatic pressure to fluid free to move in a tube will cause it to flow, and if there were no friction all the potential energy of the applied hydrostatic pressure would be converted into kinetic energy of motion. There is, however, considerable friction between circulating blood and the vessels through which it flows, and thus, much of the energy of the heart beat is expended in frictional losses.

The resistance offered by any blood vessel is related to its cross- sectional area-the larger the area of contact, the greater the resistance. The total sectional area of all the capillaries is thousands of times greater than that of the aorta or a vena cava. The sectional areas of different parts of the circulatory system are summarized in figure 46.

800

_ 700

600

500

400

300

200

100

arteries arterioles capillaries venules veins

Figure 46 A graph of the sectional areas of different blood vessels.

Resistance and the drop in pressureThroughout the circulatory system, blood pressure falls as the force imparted to blood by ventricular systole and recoil of the elastic arteries becomes dissipated in overcoming resistance. Pressure drops from 16 kPa in the aorta to 0.7 kPa in the vena cava (see figure 47).

Velocity of blood flow and surface areaThe same quantity of blood returns to the heart as leaves it, and the rate at which blood flows varies with the dimensions of the particular section of the system through which it is passing (figure 48).

All the blood expelled from the left ventricle at each systole has to pass through the aorta and velocity here is high. It will also be high in the vena cava since all the expelled blood must be returned via this route. These large vessels in which velocity is high have a small total cross- sectional area, in relation to the sectional area of all the capillaries together.


arteries arterioles capillaries

— fluctuations with systole and diastole

Figure 47A graph of blood pressure in the circulatory system.

venules

= mean pressure

arteries arterioles capillaries venules veins

= fluctuations with systole and diastole ————— = mean velocity • v

Figure 48A graph of blood velocity in the circulatory system.

Figures 46, 47, and 48 are adapted from original illustrations from Best, C. H. and Taylor, N. B. (1964) The Living body, 4th edition. Copyright 1938,1944, 1952, 1958 by Holt, Rinehart & Winston, Inc. Copyright © 1966 by C. H. Best and N. B. Taylor. Adapted and reproduced by permission of Holt, Rinehart & Winston, Inc., Publishers, New York.


The total sectional area of the capillaries is vast and the velocity of the blood within them correspondingly slow. Indeed, the graphs (figures 46 and 48) show that velocity and surface area are inversely related. Note that both pressure and velocity show fluctuations on the arterial side, owing to the pulsations of the heart.


In a model used to demonstrate certain features of the vertebrate circulatory system, coloured liquid was pumped round a continuous horizontal circuit of rubber tubing. Glass tubing of different diameters was inserted into this circuit at various places as shown in figure 49.

-about 1 m -

•—glass tubing (5 mm diameter)

rubber tubing

glass tubing (2 mm diameter)

u&

*- ~glass tubing (9 mm diameter)

-71

• — rubber tubing

one-way pump

Figure 49(j. M. B.) '•:-.'*'.

The rates of flow of the coloured liquid were measured in different parts of the circuit and the results are shown below

from A to B 0.15ms" 1 / from C to D 0.75ms" 1from E to F 0.50ms" 1

a State how the rate of flow of the liquid in a particular section of the system could be measured.

b Account for the different rates of flow1 from A to B compared with C to D;2 from C to D compared with E to F.


c Suggest how the apparatus might be simply modified to determine the pressure at different positions in the circuit.

d Whereabouts on figure 49 would you expect the rates of flow to be equal but the pressure difference to he at its greatest?

e Copy and complete the graph ('figure 50,) to show changes in pressure of blood as it passes through the vessels of a mammal. (J.M.B.)

1v>

. £a? o

arterioles capillaries

Figure 50D (J. M. B.)

3.8 The control of circulation

To fulfil its purpose, a circulatory system must adapt to the varying needs of the tissues it supplies. The two main adjustments made are in heart output and peripheral distribution; they are chiefly brought about by the action of the autonomic nervous system. This is the part of the nervous system that is not under voluntary control (see page 340). It operates automatically in response to signals received from its receptors. There are two divisions of the autonomic system, called the sympathetic and the parasympathetic systems. These two are complementary in the effects that they control, and they act to maintain internal constancy.

Adjustments to the heart

Earlier it was shown that the rate of heart beat is an intrinsic property of cardiac muscle under the control of the sino-atrial node (the pacemaker). The nervous system can impose variations on the basic rhythm, either speeding it up or slowing it down. Each adjustment made reflects an alteration of conditions detected elsewhere in the system.

Changes in blood pressure excite sensory nerve endings located in the walls of the aorta and carotid sinus, and a nerve impulse is conducted to the brain by sensory neurones. From the brain, motor impulses are


conducted to the heart by two nerves, the cardiac branch of the vagus nerve and the accelerator nerve. Impulses in the vagus nerve (a branch of the parasympathetic system) cause it to release acetylcholine from its nerve endings in the sino-atrial node and this reduces the frequency with which the node generates impulses, and so slows the heart. Impulses in the accelerator nerve (a branch of the sympathetic system) cause noradrenaline (a substance similar to adrenaline) to be released onto the sino-atrial node and into the muscle of the atria and ventricles. (See page 341 of this Guide and Chapter 24 of Study guide II.)

This increases the frequency of impulse generation by the node and also the speed and force of individual muscular contractions. Hence the cardiac frequency increases. (See figure 51.)

brain sensory nerve fibres

carotid sinus

baroreceptors(pressurereceptors)

aorta

sino-atrial node

accelerator nerve

ganglion

muscle

stretch receptor

spinal nerve

spinal cord

Figure 51A diagram to show the control of heart beat.

This dual mechanism serves to control the rate of heart beat with great precision. A rise in blood pressure means that the heart is overworking and needs to be restrained. Restraint is applied from an inhibitory centre in the medulla of the brain; the more impulses this centre receives from pressure receptors, the more impulses it sends out through the vagus nerve. This mechanism enables the rate of heart beat to be kept as slow as possible in a resting individual.

During physical activity the work done by the skeletal muscles will be voluntarily increased. This means that stretch receptors in the muscles will send out a higher frequency of excitatory signals to the medulla. These signals not only stimulate the accelerator nerve but they also inhibit conduction in the vagus nerve by acting on the medulla. So the


heart rate increases in response to a greater demand for blood by the muscles.

Adjustments to the peripheral circulation

Muscular distributing arteries and their branches are well innervated and receive a steady flow of motor nerve impulses which keep their smooth muscle fibres in a state of tone, that is, partially contracted. If the impulses stop, the muscle fibres relax and dilatation follows as a result of blood pressure. If more impulses are delivered, the muscle fibres contract more fully and the vessels become constricted.

The sympathetic nerves controlling peripheral circulation arise from two brain centres in the medulla, and as in the case of the heart centres, one of them is inhibitory and the other excitatory. As we have seen, the heart works harder during physical activity but it would be wasteful if the extra effort of the heart were to be expended in overcoming unaltered peripheral resistance. The sympathetic system brings about changes in peripheral blood vessels which allow increased work from the heart to drive blood to those organs in need of it through dilated vessels, while restricting flow to inactive regions.

A good example of this is seen when an animal is under stress that is due to fear, extreme physical activity, or pain. In the circumstances the vessels supplying the skin and the alimentary system constrict and those supplying the muscles dilate. This response results in the maximum amount of blood being distributed to the organs needing it at the expense of those whose activities can be temporarily suspended.

This redistribution would be difficult to make quickly or effectively if the blood vessels of the digestive system were fully dilated in order to cope with a heavy meal, and it is for this reason that we are warned not to swim immediately after eating because of the danger of muscle cramp.

Arterioles as pressure reduction valves

For a good supply of blood to be delivered to the tissues it is essential that blood pressure should be maintained at a high level. But if blood were to be pushed into capillaries at this high pressure they would burst. The arterioles act as middlemen, delivering blood from the artery to the capillary bed. In doing this they also bring the pressure down to a safe level and serve as pressure reduction valves. The larger arterioles are under the control of the sympathetic system; some are also innervated by the parasympathetic system. Vasoconstriction of arterioles occurs when their muscle fibres are excited to contract. Vasodilatation will occur when these muscle fibres relax and so remove the constricting force. It is also thought that the parasympathetic nerves evoke active dilatation, but the mechanism is not well understood.

The state of constriction of the arterioles is also affected markedly by certain hormones, especially adrenaline. If the body is subjected to a sudden shock or stress, the medulla of the adrenal gland pours adrenaline into the circulatory system and the sympathetic nervous system is generally stimulated. The heart rate is also stimulated by this


and cardiac output is increased, while blood is diverted from organs which are not immediately essential, such as the gut, to the brain and muscles.

Autoregulation of the capillary bed

There is no significant innervation of the capillary bed, and the control of blood flow through this region must be due to influences other than nerve impulses. The current hypothesis is that the control is chemical. By their activities, tissues produce waste substances such as carbon dioxide and lactic acid and these substances have an effect on the pre- capillary sphincter muscle ring. Excess of metabolic waste products causes the muscle fibres of the sphincters to relax, thus allowing more blood to flow into the capillary bed. The increased influx of blood would tend to wash away the waste products and so remove the dilatatory substances with the consequence that the sphincter would tend to constrict again. If the sphincter over-compensated the accumulation of waste products would once again open it up. This chemical control thus provides a nicely balanced auto-regulatory mechanism; the flow of blood is automatically adjusted to the state of activity of the tissues served by the capillary bed.

Blood loss

What happens to the circulation when an injury is sustained which results in massive blood loss? First of all, this will result in a great decrease in resistance at the site of injury. Since there will be no immediate decrease in flow rate (and since pressure = flow x resistance) the blood pressure will immediately fall. This is very dangerous since vital organs such as the brain and heart are at once deprived of blood, and therefore of oxygen. The fall in blood pressure will decrease the stimulation of the aortic and carotid baroceptors and so will release the heart from the inhibitory effect of the vagus. The heart rate will then tend to increase and this will raise the blood pressure. At the same time the injury will result in reflex vasoconstriction in organs such as skin and gut, helping to raise resistance and hence blood pressure; this will contribute also to the flow of more blood to brain and heart.

The reflex adjustments made by the body in response to the initial massive blood loss are essentially homeostatic but, because of the injury, instead of helping to re-establish normal blood pressure and flow they may increase the physiological imbalance and produce the condition known as shock.

A patient who is suffering from haemorrhage is pale, with a cold, clammy skin and a rapid pulse.

a Use the foregoing information to explain these symptoms.

b Why do you suppose that it is dangerous to give a patient who is suffering from a haemorrhage a 'nice hot cup of tea'?


Occasionally, some environmental or internal stimulus causes you to feel faint, which results from a sudden, reflex dilatation of blood vessels supplying internal organs.

Why is it likely that someone who is about to faint will become very pale ?

Can you see that any patient who has suffered an injury or some other mishap which has reduced the blood pressure is in a dangerous position? Anything that can prevent any further fall in blood pressure will aid recovery or survival, and anything that may increase the fall in blood pressure should be avoided: moving an injured organ carelessly, allowing bleeding to continue, and giving a nip of brandy are all potentially lethal. For shock is not a minor event-it is such a fundamental disturbance of equilibrium that the brain can be far enough deprived of blood for death to follow.

Drugs and the circulation

Many different drugs may be administered to a patient suffering from high or low blood pressure, to help the body's natural mechanisms of recovery to work. An example is 'beta-blockers' such as propanalol, which are used to occupy and thus block the so-called beta-receptor sites for adrenaline in the heart muscle (see page 49). The result of this is that the effects of adrenaline are less pronounced. This is of help to patients suffering from disorders of the coronary arteries and reduced blood flow to the heart in whom any sudden increase in heart activity can lead to angina or, perhaps, a more serious condition. Obviously beta-blocking will also prevent the stimulation of the heart that occurs during exercise, so very great care must be taken over dosages and the advice given to the patient must be followed.

Another well-known heart drug is digitoxin (prepared from the leaves of Digitalis purpurea, the foxglove) which acts directly upon the heart, increasing the force of contraction and the efficiency of the work done by the cardiac muscle without increasing the oxygen consumption. This is used to treat cases of cardiac oedema (congestive heart failure) where the heart has become stretched and rather ineffective.

There are many such drugs, each tailored to a particular need; the general principle is that the heart's activity is vital in controlling blood pressure which in turn influences all of the organs of the body. Any imbalance needs to be corrected quickly and carefully if the individual is to survive.


Figure 52Transport in the phloem may occur both upwards and downwards in the same plant. After Baker, D. A., Transport phenomena in plants, Chapman & Hall, 1978.

3.9 Transport inside plants

I Practical investigation. Practical guide 1, investigation 3G, ji 'Transport inside plants'.

So far in this chapter we have concentrated on transport within animals. In Chapter 8 you will be examining in detail the transport of water and dissolved mineral ions that occurs in the xylem of plants. Therefore let us turn our attention briefly here to the transport of metabolites that occurs in the phloem of plants.

The need for long-distance transport systems depends upon the size of the organism and the extent to which functions are segregated. In a higher plant, and especially in a tree, it is clear that photosynthesis occurs mainly in the leaves (although green stems also photosynthesize) but that if roots, which may be many metres away from the leaves, are to grow, the products of photosynthesis must be moved to them. This movement of the products of photosynthesis is referred to as translocation. The sites of production (where material must enter the phloem) are termed sources and the sites of use or storage in other parts of the plant are termed sinks. The rate of translocation is proportional to the gradient of concentration between source and sink tissues and usually occurs at velocities of between 50 and lOOcmh^ *. Since the sink tissue may include developing fruits, storage roots, or regions of cell division in root or shoot, it is clear that translocation in the phloem may occur both upward and downward in the same plant (figure 52 ).

Investigating the movement in the phloem

Many methods have been used to investigate both the pathway and the mechanism of transport in the phloem. One common technique uses radioisotopic carbon, 14C, supplied in the form of 14CO 2 . The 14C is fixed in photosynthesis and the sugars produced are thus labelled with the isotope, which can be detected by using either a Geiger-Muller tube or an X-ray film or by assays of ground-up plant material.

When the cells of phloem tissue are examined under the microscope several cell types may be distinguished (figure 53). These include sieve tube elements, companion cells, and parenchyma cells; fibres with thickened walls are also sometimes found in the phloem. Of these cells it is the sieve tubes, formed from columns of sieve tube elements, that provide the channels for translocation through the phloem. The sieve tube elements are highly specialized cells which occupy some 20 per cent of the phloem tissue. At maturity these elements are typically 100 to 500 urn in length; they have perforated end walls called sieve plates (see figure 53 ) and contain a unique phloem protein called P-protein. Normal cellular organelles, including the nucleus, have degenerated.

Figure 53Photomicrographs, with interpretative drawings, of a Cucurbita stem showing phloem withsieve plates.a A transverse section (x 545); b A longitudinal section (x 450).From Bracegirdle, B. and Miles, P. H., An atlas of plant structure: Volume 1, HeinemannEducational Books, 1971.


—•

section of sieve plate

pore in sieve plate


epidermis

Figure 54A transverse section showing scattered vascular bundles round the periphery of Helianthus, a non- woody stem (x 75). From Bracegirdle, B. and Miles, P. H., An atlas of plant structure: Volume 1, Heinemann Educational Books, 1971.

epideri

Figure 55Part of a woody stem, Ribes, in transverse section showing the location of phloem(x 400).From Bracegirdle, B. and Miles, P. H., An atlas of plant structure: Volume 1, HeinemannEducational Books, 1971.


Figure 56A photomicrograph showing the pathway taken by the stylet of an aphid through the epidermis of a stem ofjuniperus communis, ending inside one sieve tube element (S). The stem is seen in transverse section.From Kollmann, R. and Dorr, I., J. Pflanzenphysiologie, 55, p. 135, 1966.

The phloem in stems of dicotyledons occupies a position external to the vascular cambium (from which individual phloem cells develop) and the xylern, just under the outer tissue of the stem. The phloem may be scattered around the periphery of the stem in individual vascular bundles (figure 54) or united as a thin ring under the corky bark in woody stems (figure 55). Since the phloem is superficial its contents are easily reached by plant-feeding insects such as the aphids. The aphid is remarkably adept at manipulating its mouthparts (the stylet) and invariably

a

&•

ic^si •*" —J--»,• • i20 urn


manoeuvres the tip of its stylet so that it pierces and comes to rest in one sieve tube element (see figure 56). In a very subtle technique, aphids are used to collect fluid from the phloem for analysis.

Once the aphid is feeding it is anaesthetized and, by careful microsurgery, it is cut off from its stylet, leaving the latter as a micropipette inserted into the phloem. Since the contents of the phloem are under pressure they exude as droplets, at a rate of around Sudm 3 !!" 1 , from the free end of the stylet. These droplets can be analysed, not only to determine the 14C but also to determine the quantities of all the many substances found in the phloem. (Table 9.)

mgcm mgcm

Dry matterSucroseReducing sugarsProteinAmino acidsKeto acidsPhosphateSulphateChlorideNitrateHydrogen carbonate

Table 9The composition of phloem exudate obtained from Riclnus plants.(From Baker, D. A., Transport phenomena in plants, Chapman & Hall, 1978.)

100-12580-106absent1.45-2.205.2 (as glutamic acid)2.0-3.2 (as malic acid)0.35-0.550.024-0.0480.355-0.675absent0.010

PotassiumSodiumCalciumMagnesiumAmmoniumATPAuxinGibberellinCytokininAbscisic acid

2.3-4.40.046-0.2760.020-0.0920.109-0.1220.0290.24-0.3610.5 x 10~ 62.3 x 10~ 610.8 x 10~ 6105.7 x 10~ 6

The mechanism of movement - a continuing debate

Attempts to find out how the solution is moved so rapidly through the phloem have produced greater controversy than any other problem in the physiology of plants. Certainly, continued production of sugars at the source tissues and use at the sinks could generate hydrostatic pressure that could result in bulk movement (mass flow) in the phloem. In general terms, such events could produce a form of circulation within a plant {figure 57) but there are unresolved problems. The pores of sieve plates are very small (1 um or less) and often appear to be blocked by the P-protein material, and generally it is thought that the phloem offers too great a resistance for there to be 'unaided' movement at the rate observed. It is generally agreed that sieve tube elements are living. Energy from respiration is associated with the transport of substances in the phloem for, when radioactive assimilates are being moved experimentally in the phloem, it is possible to detect the release of 14CO2 . It seems to be more than mere coincidence that most sieve tube elements are next to a companion cell and some hypotheses suggest that these cells generate metabolic assistance. Some other ideas are summarized in diagram form in figure 58.

There are thus many ideas of how material may be moved in the phloem; they range from hypotheses based upon physical forces entirely generated by physiological loading and unloading of sugars at source and sink respectively, to those based upon sieve tubes containing highly


organized structures which use metabolic energy to propel or carry the substances along the phloem. One type of hypothesis works best if the sieve tube elements are empty of structure with freely permeable end

water evaporates into air

leaf

Figure 57Hypothetical circulation in a plant.

sucrose and other metabolites 'loaded' into sieve tubes; this lowers the water potential and water tends to be drawn in

xylem

phloem

here sucrose etc are 'unloaded'; this raises the water potential and water leaves the phloem

1 Sieve tubes contain protoplasm which may circulate within each cell. It has been suggested that materials in this stream might pass through the sieve pores into adjacent cells. This would account for substances moving in either direction at the same time.There is some evidence that such movement occurs, but not necessarily in the same tube.

2 Some workers have observedstrands of protoplasm extending

through many cells. These mayplay a part in the conduction

of substances.

~ sieve pore

-mitochondria

- transcellular strand containing endoplasmic reticulum

"parietal cytoplasm

-fluid-filled lumen

DD

3 Mass flow theories propose that materials flow through phloem cellslike waterthrough apipe.

Figure 58Three hypotheses about the movement of materials in the phloem and the possiblemechanisms that could be involved.Based on Thaine, R. 'A protoplasmic-streaming theory of phloem transport'. J. exp. Biol,15,470-84,1964.


walls, whereas for the other to be supported, the sieve tubes would have to be highly structured. The dilemma might seem an easy one to resolve-by the study of the structure of sieve tubes. However, the phloem has defied plant anatomists! Although there are many published photographs of the phloem biologists are still not sure how far they show the real structure of the living tissue.

The results of some investigations

If cuts are made in the bark of certain trees the contents of the phloem exude from the incisions. This exudate can be analysed, with results such as those in figure 59. The graphs here show the concentration of two sugars, stachyose and raffinose (relative to their concentration in the exudate from a cut 9 metres above the ground), in sap exuding from incisions made at various heights above the ground. Two sets of observations were made, one in the early summer (a) and the other in the autumn after leaf fall (b).

140

100

60

SUMMER

140

stachyose 100

o oraffinose

Height up tree at which exudate was obtained (m)

60

AUTUMN (after leaf fall)

stachyose

Height up tree at which exudate was obtained (m)

Figure 59Concentration gradients of two sugars (stachyose and raffinose) in the phloem exudatesof white ash (Fraxinus americana).a Values obtained in the summer.b Values obtained in the autumn after abscission.After Zimmerman, M. H. 'Translocation of organic substances in trees. II. On thetranslocation mechanism in the phloem of white ash (Fraxinus americana L.)', PlantPhysiol., 32,1957, pp. 399-404.

Explain how the concentrations of these sugars support a mass flow hypothesis of translocation in the phloem.


Many substances will be moved into and transported around plants if they are applied to a spot on a leaf from which the cuticle has been rubbed away to make absorption easy. If the synthetic auxin 2,4- dichlorophenoxyacetic acid (2,4-D) is applied in this way it will produce curvature in the stem if it is absorbed and translocated out of the leaf. Table 10 shows the results of an experiment in which 2,4-D was applied to leaves, in some instances together with sucrose solution, and then the plants were left in the light or the dark. (The control plants had no 2,4-D added; otherwise they were treated identically.)

Treatment Subsequent illumination Mean stem curvaturen

2,4-D light 31.0Control light 0.02,4-D dark 0.0Control dark 0.02,4-D + 10 % sucrose dark 20.4Control + 10 % sucrose dark 0.0

Table 10The effect of light, dark, and the application of sucrose on the translocation of 2,4- dichlorophenoxyacetic acid from leaves of bean plants. The degree of stem curvature indicates how much 2,4-D has been translocated.After Rohrbaugh, L. M. and Rice, E. L., 'Effect of application of sugar on the translocation of sodium 2,4-dichlorophenoxyacetate by bean plants in the dark', Bot. Gaz. Ill, 85, 1949.

b Show how these data could be used to support both the simple mass flow hypothesis and one which suggested complex metabolic intervention, to account for the translocation of the 2,4-D.

c What was the point of the treatment in which sucrose was added with the 2,4-D and then the plants were left in the dark?

Summary

1 The circulation of material throughout large organisms is essential since it may be the only way in which the raw materials for metabolism can reach cells.

2 Circulation, involving mass flow, uses energy (3.1).3 Different types of animal have different types of circulatory system,

and these systems are frequently able to vary their output to match the changing needs of the tissues (3.2).

4 There is a fundamental difference between open and closedcirculations; a closed circulation is more efficient at moving materials from place to place but has to overcome the problem of its separation from the tissues by the walls of its vessels (3.3).

5 In closed circulations tissue fluid is formed in which molecules may diffuse to the cells requiring them (3.31).

6 Some vertebrates have single circulation, but others, includingmammals, have double circulation; this makes it possible for different pressures to be maintained in the two parts of the circulation (3.3).


7 Pulmonary circulation is usually at a lower pressure than the systemic circulation and this is associated with the passage of fluid through capillary walls.

8 The different types of heart are associated with the single and double circulations; the latter enables a complex function to be performed in moving two parts of the same system at different pressures (3.4).

9 The mammalian heart is extremely complex in construction and co ordination (3.5).

10 The stimulus for contraction of cardiac muscle is internal, though the control and modification of the natural rhythm are external (3.5).

11 Nerves and hormones are able to modify the rate of heart beat.12 There are ways of examining the action of the heart which make it

possible to diagnose malfunction.13 Following such diagnosis, the surgeon may perform a heart operation

which makes it necessary to stop the heart from beating.14 Technology is continuing to try to meet the demands that are made

upon it to perform the functions of heart and lung artificially during such operations (3.6).

15 No substitute materials or methods of treating heart disease are entirely satisfactory and the fact remains that removing the cause of heart failure would help many sufferers (3.6). ,

16 As with lungs, damage to the heart is largely avoidable.17 A variety of types of blood vessel transport the blood, and the

structure of these vessels matches their functions (3.7).18 The circulation is controlled automatically by the medulla (3.8).19 Blood loss is one of the more damaging events that can occur and

reflex devices are used to attempt to correct the problems that follow haemorrhage (3.8).

20 The circulatory system is influenced by many drugs, some of which may have therapeutic uses.

21 Within plants, too, metabolites must be transported; this is done in the phloem (3.9).

22 The cells of the phloem are in many ways adapted to make thetransport of materials possible but, in spite of many hypotheses and much evidence, the exact nature of the mechanisms involved is not known (3.9).


BARON, w. M. M. Organization in plants. 3rd edn. Edward Arnold, 1979.(A thorough account of all aspects of plant physiology.)BEST, C. H. and TAYLOR, N. B. The living body. Chapman & Hall, 1959.(A comprehensive text on human physiology; the terminology seems alittle dated but there is a wealth of detail.)JAMES, w. O. An introduction to plant physiology. 7th edn. OxfordUniversity Press, 1973. (Contains a short section on translocation.)NEIL, E. Carolina Biology Readers No. 82, The human circulation.2nd edn. Carolina Biological Supply Company, distributed byPackard Publishing Ltd., 1979.


RICHARDSON, M. Studies in Biology No. 10, Translocation in plants. 2nd edn. Edward Arnold, 1975. (A lot of detail about the various hypotheses for movement of metabolites in the phloem.) ROBERTS, M. B. V. Biology. A functional approach. Nelson, 1982. VASSALLE, M. Carolina Biology Readers No. 8, The human heart. Carolina Biological Supply Company, distributed by Packard Publishing Ltd., 1979. (A detailed account of the structure and functioning of the heart.)WARREN, J. V. The physiology of the giraffe'. Scientific American, 231, (5), 1974.WOODING, F. B. P. Carolina Biology Readers No. 15, Phloem. 2nd edn. Carolina Biological Supply Company, distributed by Packard Publishing Ltd., 1978. (A slightly hard-going, but thoroughly informative account of some of the current debates about phloem.)

Chapter3 The circulatory systems of animals and plants 85

CHAPTER4 BLOOD AND THE TRANSPORT OF OXYGEN

4.1 Respiratory pigments

Practical investigation. Practical guide J, investigation 4A, 'Examination of blood'.

ColourProsthetic groupMetal in prostheticgroupMolecule of oxygenper atom of metalLocation in blood

Haemoglobinredhaem

iron

1:1cells orplasma

ColourProsthetic group Metal in prosthetic groupMolecule of oxygen per atom of metal Location in blood



Chlorocruoringreenhaem

iron

1:1 plasma

Haemocyuninbluepolypeptide

copper

1:2 plasma

Haemeiylhrin red7

iron

1:3cells or plasma

4.11

Table 11Summary of some characteristics of the four groups of respiratory pigments.

Many different animals carry in their blood a respiratory pigment whose function is to increase the ability of a given volume of the blood to absorb oxygen. Most of these pigments fall into one or other of four main groups called haemoproteins. Haemoglobins (abbreviated to Hb) are the most common and are found in vertebrates and many invertebrates; haemocyanins are found in molluscs and arthropods; and two slightly smaller groups (haemerythrins and chlorocruorins) are found in annelids. The pigments of individual members of each group, although closely related to each other, are distinct in a number of properties. Horse haemoglobin, for example, is quite distinct from human haemoglobin; human adult haemoglobin is only marginally different from human foetal haemoglobin, but the difference, a structural one, is enough to have a marked and very important physiological effect.

A molecule of haemoglobin is made up of two parts: an active, or prosthetic, part and a protein. The prosthetic part, which is the same in all haemoglobins, is a complex iron-containing compound called haem. This is the business end of the molecule, for it is here that the association with oxygen takes place. The protein part of haemoglobin consists of four short polypeptide chains known as globins.

The prosthetic group of the chlorocruorins is also haem, but is not the same as that of Hb although it is built on the same general plan. Iron is present too in the prosthetic group of the haemerythrins, although our knowledge of this group is rudimentary. The prosthetic group of the haemocyanins contains copper in combination with a polypeptide.

All these pigments do essentially the same thing. They combine freely and reversibly with oxygen, thus operating as agents which serve to transport oxygen to the tissues from the respiratory surface. At least two other factors are concerned in determining the efficiency of the blood as oxygen carrier, namely the oxgen-combining power of the pigments and the concentration of the pigment in the blood.

STUDY ITEMRespiratory pigments

Table 11 summarizes the facts mentioned above and gives the oxygen- combining powers of the pigments in terms of the molecules of oxygen taken up per atom of metal in the prosthetic group.

Which are the most efficient of these pigments in terms of the molecules of oxygen carried by each atom of metal?


Pigment Site Animal Amount of oxygen that canbe carried bv 100 cm 2 of blood (cm 3 )

Haemoglobin cells mammals 25.0birds 18.5reptiles 9.0amphibia 12.0fishes 9.0

plasma annelids 6.5 molluscs 1.5

Haemocyanin plasma molluscs:gastropods 2.0cephalopods 8.0

crustaceans 3.0

Chlorocruorin plasma annelids 9.0

Haemerythrin cells annelids 2.0

Table 12The distribution of different respiratory pigments in various animal groups, and the oxygen-carrying capacities of their blood.

Table 12 shows the oxygen-carrying capacities of bloods containing different pigments.

b Which pigment is the most efficient in terms of the concentration of oxygen per unit volume of blood?

c How can your answers to a and b be related?

There are quite a few animals whose blood consists of virtually nothing but more or less diluted sea water. (100 cm 3 of sea water can contain about 0.5 cm 3 of oxygen.) They are usually comparatively sluggish, slow moving or sedentary creatures.

d How would you account for these facts?

Human blood can carry one quarter of its own volume of oxygen. The blood of seals, and other diving mammals possessing haemoglobin at very high concentration, can carry as much as a half of its volume of oxygen. The lugworm, Arenicola, lives in a burrow in the sandjust above low water mark. It possesses blood with haemoglobin, but not in cells. When it is covered with well-oxygenated sea water the worm carries all the oxygen it needs in simple solution in its blood plasma. At low tide, the lugworm retreats to its burrow and shuts itself in, being more or less cut off from external sources of oxygen. As the oxygen tension in its blood falls, it begins to use the combined oxygen of the haemoglobin present in the plasma; there is just enough haemoglobin to'carry it through the period during which it is shut off from the sea.

e What additional function does haemoglobin appear to serve in diving D animals and Arenicola compared with terrestrial animals like humans ?


The structure of haemoglobin

Practical investigation. Practical guide- /, investigation 4B, 'The carriage of oxygen'.

&•&" '''.'ibi^™' i-™1 •::• si " .2 ItiliH

We have stated that haemoglobin (Hb) is made from two parts, haem and globin. Let us explore the structure of this molecule a little more thoroughly, since it is the way in which the molecule is put together that is responsible for most of its remarkable properties.

Each molecule of Hb consists of four globin chains, each one linked to its own iron-containing haem group (figure 60). All the haems are identical, in every type of Hb, but the globins are not. The three most common types of globin in Man are referred to as alpha, beta, and gamma. Adult Hb contains two alpha globins and two beta globins, in contrast to the human foetal Hb which is composed of two alpha chains and two gamma chains.

The Hb molecule picks up and binds four oxygen molecules, one for each haem group. The haemoglobin does not become oxidized in the process, and the iron atoms of its haem groups remain in their iron(n) state all the time. The oxygen molecules have to fit into pockets on the Hb which are called binding sites. This is not easy because the polypeptide units of the deoxyhaemoglobin are bound together in an awkward configuration by so-called salt-links (these are not unlike hydrogen bonds). We say that deoxyhaemoglobin is in the tense (T-form) configuration because the salt-links make binding to oxygen hard. However, when oxygen molecules begin to bind to the Hb, these salt-links are disrupted and the affinity of the molecule for oxygen increases. Its configuration takes the relaxed form (R-form). So the more oxygen that is bound, the greater the affinity for oxygen. This remarkable property, often called cooperative binding, has a number of physiological implications.

Cooperative binding is the principal cause of the shape of the dissociation curve of Hb, which is sigmoid (S-shaped). (Myoglobin, which has only one globin chain and only carries one oxygen molecule, has a hyperbolic curve as mfigure 63.) It is also the underlying cause of the Bohr effect (see page 92). Carbon dioxide binds to Hb; not to the same site where oxygen is bound, but to another (allosteric) site. This binding serves to increase the salt-linking and stabilize the deoxyhaemoglobin, thereby decreasing the affinity of the molecule for oxygen. Likewise, protons have a very similar effect. Both protons and carbon dioxide are in high concentration in areas where greatest metabolic activity is going on, and it is here that the need for oxygen by the active tissues is at its greatest. Conversely, where the environmental partial pressure of oxygen (po2 ) is high its pressure promotes the release of carbon dioxide and protons.

Free Hb in solution has a greater affinity for oxygen than Hb in red blood cells has. This suggests that some feature of the red cell complex stabilizes the T-form of Hb. 2,3-diphosphoglyceric acid (DPG) (see page

Maintenance of the organism

Figure 60A model of the haemoglobin molecule as deduced from X-ray diffraction studies. In this model, the alpha globin chains are light and the beta chains dark grey. The haem groups are represented by the black discs. After Perutz, M. F., 'The haemoglobin molecule'. Copyright © 1964 by Scientific American, Inc. All rights reserved.

114) binds to Hb and reduces its oxygen-affinity markedly. If DPG were not present in the cells, there would be such a great affinity for oxygen that there would be no release of it until a p02 of around 0.3 kPa were reached.

Let us now turn back to our investigation of Hb at work and try to explain what we observe in the light of our knowledge about this truly remarkable molecule.

Po2 (kPa)

123456789

1011121314

Percentage saturation of Hb with oxygen

8.523.640.357.571.279.885.389.092.1.94.095.596.597.398.2

Table 13Percentage saturation of haemoglobin at different p02 , at pH 7.4 and 38 °C.

STUDY ITEM4.12 Haemoglobin and the carriage of oxygen

Each red blood cell contains around 280 million molecules of haemo globin. Each of these molecules can carry four molecules of oxygen, one associated with each of the iron atoms on the Hb. The reaction between oxygen and Hb is reversible in that oxygen is taken up where it is plentiful, as at a gas exchange surface, and released where it is scarce, as in the working tissues. When fully saturated, 1 g of Hb contains 1.34cm 3 of oxygen. As 100cm 3 of blood contain around 15 g of Hb, each fully saturated 100cm 3 of blood will contain around 15 x 1.34 = 20.1cm 3 of oxygen. Oxygen and Hb combine rapidly when the partial pressure of oxygen (p02 ) is high, and the oxygen is released (dissociates) rapidly from oxyhaemoglobin when the p02 1S l°w- Table 13 presents the percentage saturation of Hb with oxygen at different partial pressures of oxygen.

a Using the figures from the first column of table 13 as the abscissa, plot a graph of p02 against the percentage saturation of Hb.

The curve you have obtained is called the oxygen haemoglobin dissociation curve. (Partial pressures are explained fully on page 14.)

b In the lungs of a man the p02 is 13.3kPa. What is the percentage saturation of Hb at this level?

Chapter 4 Blood and the transport of oxygen

c In the venous blood the />02 is 5.3 kPa. What is the percentage saturation at this level?

d When fAe/>02 of blood is low, is the percentage saturation of the Hb high or low?

e When the p0l of blood is high, is the percentage saturation of the Hb high or low?

f Is the relation between p^ and percentage saturation a linear one?

g Consider the top of the curve, in the p^ range 6 to 14kPa. Would a large change in pOl (say 2 kPa) have a small or large effect on the amount of oxygen carried by the Hb ?

Atmospheric pressure is 101.3kPa. The following values of the percentage of oxygen in the air were obtained from a human subject indoors:percentage of oxygen in the atmosphere 21.0 percentage of oxygen in expired air 16.5

h Calculate the partial pressure of oxygen1 in the atmosphere; and /2 in the expired air.

i Is there likely to be much variation in the amount of oxygen loaded into Hb at the lungs because of variations in the oxygen content of the atmosphere ?

j What is the effect, on the amount of oxygen carried by the Hb, of small changes inp0l within the range I to 5kPa?

k The p0l in tissue fluids ranges from 0.7 to 4.0 kPa. What will be the influence of this low partial pressure on oxy haemoglobin?

1 If more oxygen were used in the tissues because of exercise, what would D be the effect on the dissociation of oxy haemoglobin?

STUDY ITEM4.13 The oxygen haemoglobin dissociation curve

The relation between the degree of saturation of blood with oxygen and the partial pressure of the gas in the blood's environment is not a static and inflexible one. As was pointed out earlier, the presence or absence of other factors can alter the degree of internal bonding (salt-links) within the haemoglobin molecule and hence change its affinity for oxygen. Any changes in these factors will have effects that are reflected in the dissociation curve.

Figures 61 and 62 show the relation between two different environmental factors and the form (shape and steepness) of the dissociation curve.

a Describe, in general terms, the effects that these factors have on the form of the curve.


c lOOr • 10 °C 20 °C

Figure 61The effect of temperature on the form of the dissociation curve.

Figure 62The relation between the partial pressure of carbon dioxide and the form of the dissociation curve.

100r

A = pco, 2.7 kPa

B = Pco 2 5.3 kPa

C = PC0 2 10.7 kPa

10 12 14

PC, (kPa)

b Consider blood in an environment at a p02 of 2 kPa. What is the effect of1 increasing the temperature from 20 °C to 38 °C; and2 increasing the Pco 2 from 2.7 kPa to 10.7 kPa?


The effect of the increasing partial pressure of carbon dioxide on the dissociation curve is called the Bohr effect after one of its discoverers, Christian Bohr, father of the eminent Danish physicist, Niels Bohr.

c What influence would you expect increasing body temperature to have upon the Bohr effect ?

d Of what practical value are these effects for a tissue such as exercising muscle ?

We have already noted the apparent adaptability of haemoglobin. However, there are even more subtle and striking examples of pigments that, by their location or exact chemical nature, are part of a battery of adaptations that help organisms to occupy very particular physiological or ecological niches. Consider, for instance, the activities of a dogfish - a fish that may spend much of its time slowly cruising through calm waters. Occasionally it may require a sudden turn of speed to escape a predator or to apprehend prey.

100

O)'5.

A = haemoglobin

B = myoglobin

10

Figure 63The dissociation curves of haemoglobin and myoglobin.

12 14 16

Po2 (

If the tail of a dogfish is examined, it is found that the bulk of the muscle is 'white' or 'twitch' muscle, that is used only during the brief periods of violent activity. There is also an outer layer of'red' or 'tonic' muscle that is used in the slow, prolonged contractions of the slow cruising. It is known that the 'tonic' muscles contain large concentrations of myoglobin ('myo-' means muscle) - the pigment that is structurally similar to one of the four polypeptide chains of haemoglobin. Myoglobin can carry oxygen, and figure 63 shows its dissociation curve together with the curve for haemoglobin.


e If fully saturated blood passes through the 'tonic' muscle when its p02 is 5kPa, what will be the effect on the saturation of both the haemoglobin and the myoglobin'!

f Describe how this muscle tissue may obtain oxygen if its p02 falls from 5 to 3 kPa and then from 3 to 1 kPa during particularly prolonged activity.

Muscle tissue can grow fatigued and lose its ability to contract and relax if it runs short of metabolites.

Figure 64The dissociation curves of Man and Arenicola. Based on Redfield, A. C. 'The haemocyanins', Biol. Rev., 9,pp. 175-212,1934.

JD

Suggest how the presence of myoglobin in these muscles may contribute to the fact that they seldom show any signs of fatigue. What other feature of these 'tonic' muscles would you expect to find as part of their protection from fatigue ?

The annelid worm, Arenicola, was mentioned in Study item 4.11. The graph in figure 64 compares the dissociation curves of Arenicola and Man.

100r

an pH 7.47

h Describe the differences in the relation between percentage saturation andpO2 for the two animals.

i To what extent do these differences reflect differences in the environment and way of life of the species?

There would seem to be several stages in the evolution of an efficiently functioning blood. These are summarized below, but not necessarily in evolutionary order:1 increased concentration of pigment;2 a composition similar to sea water;3 the production and incorporation of a respiratory pigment;4 the production of blood cells;5 a dissociation curve which has a marked S-shape.

Arrange these stages in the order in which you consider they might have occurred. Explain the reasons for your choice.



The table below gives the percentage saturation with oxygen of haemocyanin, the blood pigment of the cuttlefish (Sepia sp.) at a low and a high concentration of carbon dioxide.

Partial pressureof oxygen

123456789

1011121314

Saturation of haemocyaninwith oxygen at

low concentrationof carbon dioxide

10 3053778997

100100100100100100100100

high concentrationof carbon dioxide

4 101830445973838993969899

100

D

Express these results graphically to show the relationship between partial pressure of oxygen in kPa and the percentage saturation of haemocyanin with oxygen.

What two pieces of information does the shape of both curves give about the possible usefulness of haemocyanin as an oxygen carrier in the living animal?

Using the graph, determine the partial pressure of oxygen when the haemocyanin is 50 % saturated with oxygen at a low concentration of carbon dioxide.

If this partial pressure of oxygen in c is kept constant, but the concentration of carbon dioxide is increased from the low to the high, what will be1 the effect and2 the resultant percentage saturation of the haemocyanin with oxygen?

How is the effect given in d of use to the living animal? (J.M.B.)

94 Maintenance of the orga

4.2 When oxygen is scarce

So far we have considered the operation of the circulatory and gas exchange systems in a variety of organisms under what could be called ideal conditions when all the requirements for a normal existence are fully satisfied. We have suggested that adjustments may be made to enable the organism to survive when environmental conditions change, and we are now going to consider in more detail the ways in which these two systems cope with the stress that is put upon them by scarcity of oxygen.

Exercise and training

In order to understand how the adaptations for exercise work, it is necessary to understand a little about respiration (see pages 152-160). In this process a chemical substrate is broken down and the energy that is released is transferred to ATP and thence to the working muscles. Respiration is generally aerobic, that is, it uses oxygen to break down glucose, and the only chemical waste products are water and carbon dioxide. Most muscle tissue, however, also respires anaerobically. Anaerobiosis does not use oxygen and produces not only water but also lactic acid (lactate) as waste products. Lactate is toxic if allowed to accumulate so, after a period of activity has ended, it has to be converted back to glucose or changed to carbon dioxide in aerobic respiration. Obviously, the amount of lactate that is formed during exercise determines the amount of oxygen needed for its conversion after the exercise is over. This oxygen is referred to as the oxygen debt; there is a limit to the oxygen debt which any individual can sustain.

Consider a male athlete. The amount of work that he can do in a given time will be determined largely by the amount of oxygen that he can absorb in that time and the extent of the oxygen debt that he is able to sustain. If we assume that for every dm 3 of oxygen available to him he can generate around 20 kJ it is possible to calculate how much energy he can make available for doing physical work. For example, suppose he can absorb oxygen at a maximum rate of 2.5 dm 3 minute ~ 1 and can sustain a maximum oxygen debt of 10dm 3 : over a race lasting 3 minutes he can generate [(2.5 x 3) + 10] x 20 = 350k-J. Of course, his muscles are inefficient at converting this into physical work and a figure of around 20 per cent is not unreasonable. So the individual in our example could perform a maximum of 70 kJ of work. When athletes compete, one of the major factors determining who wins is which of them has the largest amount of oxygen available to him or her in terms of consumption and debt.

Training must be designed to increase the rate at which an individual can absorb oxygen, and it is this which is used as a measure of physical fitness. (Of course, it is difficult to measure maximum oxygen consumption in field conditions, but there is an almost linear relation between that and heart rate, so maximum heart rate is used instead.) It should be remembered that not all tasks are equally dependent upon aerobic fitness. A trained sprinter, for example, takes less than 10 seconds to run 100 metres. It has been calculated that this requires 6dm 3 of


oxygen, of which 0.5 dm 3 or less is inspired during the run, so that an oxygen debt of 5.5dm 3 or more is built up. So this activity is largely anaerobic and only around 8 per cent aerobic. Virtually all field events - javelin, discus, and the jumps - are almost entirely anaerobic. A track event lasting a little longer than the sprint, such as a 400-metre race lasting 50 seconds, will be about 80 per cent anaerobic and 20 per cent aerobic and a 2000-metre rowing event lasting 6 minutes will be perhaps 55 per cent aerobic and only 45 per cent anaerobic. This means that an athlete can be advised to choose an event to complement his or her own specific capacities and, more important, to train appropriately for that event. For example, rugby training was almost revolutionized when it was realized that it was explosive rather than continuous and hence contained brief periods of intense activity which were largely anaerobic rather than the sustained aerobic exercise that required aerobic training such as lengthy, slow runs.

By training, an athlete can modify several other characteristics besides the one mentioned above. The maximum oxygen debt that can be incurred by an untrained individual rarely exceeds 8 to 10dm 3 , but good athletes can double this figure. Efficient use of the muscles is also improved by training and the cardiac output (the volume of blood pumped per minute) can be greatly increased. > ,

STUDY ITEM4.21 The effects of training

Table 15 is a summary of the main changes that take place in a variety of functions as a result of training. All the figures are, of course, approximate.

a From the data in the table calculate the cardiac output in dm3 minute~ l of the three athletes at rest.

b Which of the rows of data indicates most directly the athletes' ability to sustain oxygen debt ?

c Describe the changes that have occurred to the heart as a result of the training in the international athlete compared with the pre-trainingathlete.

d Why do you think that there are no data given for ventilation apart from its rate ?

e There is a very big difference between the data for the normal individual after training and those for the international athlete. Apart from the duration and extent of the training, what is the main factor determining the features such as maximum cardiac output and maximum oxygen uptake ?

f Explain briefly the method by which you would obtain a value for D maximum oxygen uptake (Vo2ma-J.

The second aspect of training concerns the most efficient use of the athlete's physical capabilities. To run a marathon, it is not enough


Measure

Heart rate at rest (beats minute" 1 )

Stroke volume at rest (cm 3 )

Stroke volume, maximum (cm 3 )

Heart volume(cm 3 )

Ventilation rate at rest (breaths minute ' )

Ventilation rate, maximum (breaths minute " ' )

Lung capacity (dm 3 )

Vo2 rest (cm 3 kg" 1 minute" 1 )

Ko 2 maximum (cm 3 kg" ' minute" 1 )

Lactate at rest (mglOOcm" 3 )

Lactate, maximum (mglOOcm " 3 )

I're-lruining

11

64

120

750

14

40

7.2

3.6

40

20

110

Post-training

58

79

140

820

12

45

7.2

3.8

50

20

125

International

36

128

200

1200

12

55

7.4

4.1

77

20

185

Table 15Summary of the changes taking place in a variety of cardiovascular and respiratory measures for a normal individual before and as a result of training. The equivalent figures for an international athlete are also given. All figures are approximate. (1/o 2 = oxygen uptake.)

simply to have the ability to deliver enormous quantities of oxygen to working muscles for a short time. The best runners are those who can maintain a level of energy expenditure, and hence of oxygen consumption, which is as close as possible to their maximum.

A runner who can maintain 85 per cent of a K02 max of 70cm3 kg" 1 minute" 1 will go faster than one who can only maintain 70 per cent of a higher consumption such as 80 cm3 kg " 1 minute~ ! . This may seem a small difference but modern competitive sport is decided by much smaller percentage differences than this.

STUDY ITEM4.22 Oxygen debt

What happens if the first runner mentioned above runs at a higher rate of consumption than the 85 per cent quoted? If, in practical terms, 85 per cent of the V02mm is the maximum he or she can maintain for long periods, then the runner has to obtain the additional energy from anaerobic sources. In other words, for this runner 59.5 cm 3 kg" 1


minute ' is the anaerobic threshold. With training this threshold can be elevated to come closer and closer to the K02max- If the runner just dips into anaerobic energy sources for a few seconds then there will probably be no apparent penalty; but if the requirement is for more than six seconds or so then anaerobic respiration will be used in earnest and the penalty will be the generation of lactic acid, whose protons cause interference not only within the blood but also within the muscle cells. Lactic acid is one of the main causes of fatigue when muscle is forced to respire anaerobically.

a What short-teym beneficial effect will the athlete gain from the presence of lactic acid in the blood?

Obviously, training for a particular event, such as a 1500-metre track event, will have an important object besides improving general fitness and increasing the capacities mentioned under 'Exercise and training'. It will concentrate upon ensuring that the athlete does not arrive at his or her maximum oxygen debt before reaching the winning tape. In any race, the maximum amount of energy that can be expended is given by the maximum oxygen uptake for the duration of the race plus the athlete's maximum oxygen debt.

Suppose that an individual may incur an oxygen debt of 15 dm 3 . To run at 8 metres per second he requires oxygen at the rate of 0.2 dm 3 per second. His maximum rate of oxygen absorption is 4.0 dm 3 minute" 1 .

b How far can he run at this speed before becoming completely exhausted?

c What proportion of the energy that he has then used is associated with the oxygen debt ?

This amount of energy will need to be 'repaid' after the race is finished. Figure 65 represents the demand and usage of oxygen by a runner during a short period of vigorous running. By the end of the race the subject was completely exhausted and could run no further.

d From the graph, what is the approximate value of the maximum oxygen debt substainabk by this athlete ? A 12dm3 B 21dm3 C 33dm3

e What is represented by the three areas, L, M, and N on the graph ?

f What is the maximum rate of oxygen consumption by this athlete?

Two runners, A and B, can sustain maximum oxygen debts of 15 and 10 dm 3 respectively. Additionally A has a Ko 2 max of 3 dm 3 minute" i and B has a K02max of 4dm 3 minute" '. The two runners are matched in two races. One race is over 400 metres and takes about 50 seconds to complete; the other is over 5 kilometres and takes about 14 minutes to complete. The runners are of the same mass and operate with the same muscular efficiency.


12r

10-

9-

7 -

6-

5

4

3

2

1

01 9 10 11 12 13 14 15

Time (minutes)

Figure 65The demand and use of oxygen by a runner during a period of vigorous exercise. (The solid line represents use of oxygen; the broken line represents demand.)

D g Which runner will win each of these two races?

Diving birds and mammals

When an aquatic bird or mammal dives for food it has only the oxygen contained within its body at its disposal. As far as gas exchange is concerned, the animal is completely isolated from its environment. Mammals, such as the Weddell seal and sperm whale, can remain submerged while voluntarily diving for one hour or more, and the emperor penguin can do so for 15 minutes (see table 16). Some of the earliest experiments on the physiology of diving were performed on domestic ducks. In 1870, by feeling the pulsations of a duck's heart through its breast, Paul Bert discovered that if the head of a duck were placed under water, its heart rate fell from 100 to 14 beats minute"' and remained at this level for the whole time that the animal was submerged. (Reduction in cardiac frequency is called bradycardia.) In 1899 another French physiologist, Charles Robert Richet, calculated that a duck 1.5kg in mass has an oxygen store of 90cm 3 . He found its resting oxygen consumption to be 30cm3 minute" 1 and yet it could survive submersion for more than 10 minutes without apparent signs of discomfort. It was concluded that oxygen consumption must be greatly decreased during a dive. This conclusion was supported by Scholander's work on ducks, penguins, and seals where he showed that the oxygen consumption at the end of a dive was lower than would be expected if aerobic metabolism had continued at the pre-dive rate during submersion. It was also found that the concentration of lactic acid increased greatly in skeletal muscle during the period of submersion but it was only upon surfacing that it increased substantially in the blood. All


these data were taken to indicate that during submersion there is restricted blood flow to most of the body (muscles, skin, intestine, kidneys) and anaerobic metabolism occurs there. Blood does, however, continue to supply the central nervous system and heart, which cannot withstand oxygen lack to any great extent. Blood pressure is maintained at near normal levels as a result of the reduction in heart rate and output. This set of adjustments is usually termed the classic diving response.

STUDY ITEM4.23 Diving and the use of oxygen

Something rather puzzling about ducks was that, when their heads were submerged, it took an average of 60 seconds before the bradycardia and vasoconstriction were at their maximum; yet with the exception of penguins, most, birds do not dive naturally for much longer than one minute (see table 16).

a State concisely what these facts suggest about the use of oxygen by these birds during diving.

To investigate natural dives, a method of recording physiological data from freely diving birds was required. A small radiotransmitter was used by Butler and Woakes in 1976 to record the heart rate of freely diving tufted and pochard ducks. It was noted that the ducks usually performed several dives in a series. Figure 66 shows part of a recording made during a series of six dives.

RestFirst spontaneous dive Last dive (of 6)

c in

CQ OUt .

„ f 400

£ 200

003-

Time (s)Figure 66Traces showing the heart rate and ventilation frequency associated with the first and last spontaneous dives of a series performed by a male tufted duck. The periods when it was submerged are indicated by the vertical dashed lines.Adapted from Butler, P. J. and Woakes, A. J., 'Changes in heart rate and respiratory frequency during natural behaviour of ducks with particular reference to diving,' J. exp. Biol.,79, 1979, pp. 283-300.


Describe the main differences between the heart rate1 immediately before2 during3 immediately afterthe two dives shown in figure 66 and the heart rate at rest (the part ofthe trace marked A).

From the evidence of figure 66, would you say that these ducks employ oxygen-conserving adjustments during spontaneous dives?

Figure 67 gives the mean rate of heart beat for tufted ducks in various conditions of exercise. Note that there is no significant difference between the oxygen uptake during a voluntary dive and the uptake while swimming at maximum sustainable speed. Despite this similarity, the heart rate during the voluntary dive is significantly lower than the rate during swimming (although it is still 2.6 times as great as during involuntary submersion). From all this evidence it is suggested that the cardiovascular adj ustments in tufted ducks during voluntary diving result from the opposing influences of exercise and the classic diving response, with the bias towards the former; it is also concluded that voluntary dives are usually completely aerobic.

^~ 300

» 200-

100

voluntary dive swimmingrest involuntarydive i

1/0 2 = 0.57 cm j s~

Figure 67The average heart rate of tufted ducks at rest, 15 seconds after involuntary submersion, during voluntary dives of 14.4s mean duration, and while swimming. Adapted from Woakes, A. J. and Butler, P. J. 'Swimming and diving in tufted ducks, Aythya fuligula, with particular reference to heart rate and gas exchange', J. exp. Biol., 107, 3/7-29, 1983.

Similar adjustments seem to occur in mammals. Kooyman and his colleagues discovered in 1980 that only 123 out of 4600 dives recorded from Weddell seals freely diving in the Antarctic were longer than 26 minutes and that it was only after these unusually long dives that there was any increase in blood lactate. After an hour-long dive, blood lactate reached 50 times the resting value and took 2 hours to return to normal.


When the seals were diving for 8 to 25 minutes rest periods lasted for only 2 to 3 minutes.

d Feeding periods for the Weddell seal may last for as much as 10 hours. What advantage does this seal gain by diving aerobically?

e If aerobic diving is used for feeding, under what circumstances would you expect the seal to use its anaerobic diving capacity?

Diving in humansAlthough the whole question of the physiological responses to breath- hold diving in Man could perhaps be reinvestigated in view of the recent findings in ducks and seals, there are, nonetheless, examples of the classic diving response being a life-saver in Man. At birth, after the placenta has ceased to provide oxygen to the newborn baby, there is a period before lung ventilation begins, during which the baby becomes progressively asphyxia There is evidence to suggest that the baby may be protected by a diving-type response of selective vasoconstriction and anaerobiosis in certain tissues. Such a response is also no doubt the reason for a number of authenticated instances of people surviving complete accidental submersion for up to 40 minutes.

Problems of diving to great depthsLimited oxygen supply is not the only problem encountered by diving animals. Many dive deeply into the oceans and this may take them to regions where food is relatively abundant. At the same time, however, they experience physiological problems which are all related to the fact that the animal submerges with some air in its body. For every 10 metres of descent the external hydrostatic pressure increases by lOf kPa, and air in a compressible container (such as a lung) will have its volume reduced in proportion to the increase in the surrounding pressure. So if there is air in the lung during the dive, the partial pressure of the individual gases will rise and they will enter the blood. As nitrogen is inert it will accumulate in the blood and tissues and may cause narcosis. If ascent after the dive is too rapid to allow this nitrogen to leave the blood via the lung, it will form bubbles in the blood and tissues (the condition called decompression sickness or Caisson disease) and may lead to death. All body fluids are at the same pressure as the surrounding environment, so if the volume of air in the lungs is not reduced sufficiently during descent (for example, if the chest wall is not sufficiently collapsible) for its pressure to increase to that of the blood, there will be too great a pressure difference between the blood and the air. Therefore capillaries will rupture, producing pulmonary oedema (commonly known as 'the squeeze'). Birds and mammals do dive deeply, and sometimes quite rapidly (see table 16), so they must somehow avoid these problems.

An important factor in avoiding both squeeze and decompression sickness is to eliminate gas from the air spaces that are lined with soft tissues; this includes the sinuses (air-filled spaces in the bones of the head around the nose) as well as the lungs. The lungs may be compressed until the only air remaining in them is the residual volume. When the thorax is fully compressed the lungs still contain about 20-25 % of their total


Tufted duckGreat northern diverEmperor penguinSea otterCalifornia grey whaleWeddell sealSperm whaleMan(assisted pearl divers)

Average duration of dive

20 25s (at 2m)47s2. 5-9 minutes57s4 minutes8-25 minutes10-20minutes1-1. 5 minutes(at 10- 25m)

Maximum recordedduration of dive

40s62s15 minutes4.25 minutes16. 5 minutes70 minutes1 h (possibly 2 h)approx. 3 minutes(at 30- 40m)

Maximumrecorded depthof dive (m)

660

26520

170600

2250100

Table 16Dive durations and depths of some aquatic birds and mammals.

capacity. Maximum compression is normally reached when external pressure on the thorax corresponds to a depth of 30-40 metres.

The man that performed the breath-hold dive to 100 metres (see table 16) may have had an extraordinarily collapsible chest. The only reliable way to remove the possibility of pulmonary squeeze and potentially fatal absorption of nitrogen in mammals that dive deeply for long periods, is to eliminate gas from the delicate exchange regions of the lung. Scholander in 1940 suggested that as a result of the oblique position of the diaphragm, a compliant thorax, and reinforced air passages in the lung, gas could be progressively displaced from the alveoli into the dead space during descent until eventually the alveoli collapsed completely. To this end the bronchioles of seals, dolphins, and whales are reinforced either with cartilage or by a layer of oblique muscle. The seals partially expire before submersion. Unlike seals, whales and dolphins dive with a full lung but their thorax is very compliant, probably as a result of the reduction in the number of true ribs and the oblique position of the diaphragm as postulated by Scholander. Data from bottle-nose dolphins indicate that total alveolar collapse does not occur until a depth of approximately 70 metres is reached and that these animals reach this depth very quickly indeed after leaving the surface.

f Explain briefly the ways in which each of the adaptations mentioned in D the preceding paragraph may be of advantage to the diving mammal.

Breathing at high altitude

'High' in this context is taken to mean about 3000 metres. When unacclimatized people ascend to this elevation, they usually experience breathlessness, severe fatigue, headache, and perhaps nausea. Many areas of the World are higher than this and are visited by climbers, but in the Himalayas and the Andes people live permanently at this altitude. There is however a critical altitude of about 5500 metres, above which


successful permanent acclimatization does not seem to take place. Native Highlanders (called Quechuas) of the Peruvian mining community of Auconquilcha live at an altitude of 5330 metres and climb an extra 450 metres each day to work but refuse to sleep at this height. Thus around 5800 metres could be considered an upper limit for permanent daily commuting!

Features that are found in humans living permanently at high altitudes include:Hyperventilation - the volume of air breathed per minute is 25 to 35 per cent greater than is normal at sea level; this is chiefly because of greater tidal volumes at each breath rather than increased rate of breathing. Reduced alkali reserve - hyperventilation, whether at sea level in a classroom or at high altitude, leads to the loss of more carbon dioxide than would otherwise occur. This leads to a rise in blood pH which is compensated for by the excretion of hydrogen carbonate ions by the kidneys. There follows a reduction in the total blood hydrogen carbonate level which restores the blood pH to its former value. Increased lung surface area — high altitude peoples tend to have rather barrel-like chests and it may be that they have a greater lung surface area; they do have a greater residual volume and vital capacity. More capillaries - there is evidence that the number of capillaries per unit area of muscle increases by 25 per cent or more. This facilitates the diffusion of oxygen by reducing the distance the oxygen has to travel and by increasing the unit blood flow. Capillaries increase in number by a form of 'budding' which may occur in response to anoxia (absence of oxygen) or, in the laboratory, electrical stimulation; what actually triggers this 'budding' is as yet unknown.More myoglobin - increases in myoglobin are about 25 per cent, although the stimulus for synthesis of this protein is not known. More haemoglobin - in the Quechuas the haemoglobin concentration is 200mgcm~ 3 compared with a sea level 'normal' of 150mgcm~ 3 . This comes from a red cell count of 6.4 x 10 12 dm~ 3 , compared with a sea level value of 5.1 x 10 12 dm~ 3 .Changes in mitochondria (the organelles in the muscle which perform many of the reactions of respiratory metabolism)-these increase in size and number.

There are many other body changes at this altitude, including a lowering of muscle glycogen and alterations in hormone levels (for example renin, aldosterone, and erythropoietin), but the factors described above are important in the main steps involved in oxygen transport. They form a very good example of adaptability of function at the cellular and biochemical level, to cope with fairly extreme changes in external and hence internal environment.

Visiting high altitudes - the mountaineerMount Everest is 8848 m high and there are many peaks over 6000 m, all visited increasingly by teams of climbers and to some extent by runners, skiers, and even canoeists. The Mike Jones expedition in 1976 canoed down the Dudh Khosi from its source at 5334m on Everest; Miura, a Japanese skier, descended the mountain from 8000m in 1970; and


Adrian and Richard Crane ran the length of the Himalayan chain in 1983. High altitude running is becoming popular, dangerous though it is. The two main problems faced at such altitudes are cold and lack of oxygen. There is a third factor, the loss of physical fitness in terms of muscle strength and local muscle endurance. It has been shown that at higher altitudes the climber progressively 'detrains' because he or she simply cannot work hard enough to maintain the fitness levels acquired at lower altitudes. At an altitude of 6000m the upper level of ventilation is 100dm 3 minute" 1 , of which about 2.3dm 3 are extractable oxygen; this amount provides about 48 kJ of energy each minute. (It has been calculated that, at s.t.p., a human produces 20.18kJ for every dm 3 of oxygen consumed.) 30 kJ are released as heat each minute, which is only half to one-third of the corresponding heat production at sea level; this means that the climbers cannot keep warm simply by physical activity. A combination of cold and hypoxia (low oxygen concentration) can lead to a strong desire to sleep which may be fatal.

It is, of course, possible to carry oxygen for supplementary use at higher altitudes but the extra oxygen available is partly used by the extra energy required to carry the heavy equipment, although on balance it has usually proved worth while. Nevertheless, more and more mountaineers climb Mount Everest without the use of extra oxygen.

Altitude Problem (m)

6000 The climber starts to need supplementary oxygenbecause of exertion.

12000 It is essential to breathe pure oxygen continuously. 15000 Even pure oxygen at this altitude is ineffective. 19 000 Blood plasma and other body fluids boil at 37 °C at this

altitude but note that death will already have occurred from hypoxia.

Table 17Extra oxygen requirements at increasing altitude.

Flying at high altitudesPeople ascend to high altitudes by a variety of devices such as powered aircraft, gliders, balloons, and spacecraft. It is possible to create an artificial atmosphere around a person, as in a pressurized cabin or suit supplied both with oxygen and with a means to absorb carbon dioxide. Thus, it is possible to ascend to any altitude, including those where the condition of weightlessness indicates a height at which there is virtually no atmosphere at all. The oxygen lack becomes noticeable at around 3700 m, and above 6000 m, unaided balloonists or those in unpressurized aircraft may lose consciousness. Commercial airlines increase their cabin pressure to a level equivalent to that of around 2500 metres, and should such a cabin be punctured (by a hijacker's bullet for example) then the captain has to dive to an acceptable altitude of, say, 3000 metres or the passengers lose consciousness. The high altitude balloonists take oxygen with them and astronauts only venture outside the pressurized confines of their craft in very sophisticated suits designed to resist cold, radiation, vacuum, and hypoxia.


The newborn baby

At the time of birth all of the functions in the baby which, during pregnancy, have been performed by the mother have to be taken over by the newborn infant. Then the systems which perform these functions have to mature. The various systems in the body achieve maturity at different rates - the central nervous system matures over a period of years, while the renal system matures in months. By contrast, the cardiovascular and respiratory systems are obliged to become relatively mature within a few hours, so it is hardly surprising that occasionally this massive adaptation fails. Such failure accounts for many of the medical problems of the newborn, and these problems are naturally more common and more severe in babies born early and, therefore, when they are less mature.

Figure 68In prematurely born infants many functions which have not yet matured have to be temporarily taken over by artificial means. In the centre of this photograph an incubator provides warmth and humidity and protects the infant from a hostile environment. On the left a ventilator takes over from the infant's breathing, while on the right fluids and nutrients are infused directly into a vein. On the far right, equipment monitors the infant's arterial oxygen concentration and heart rate. Photograph, Department of Medical Illustration, Southmead General Hospital, Bristol.

The foetal circulationTo appreciate the changes which occur at birth you must understand the differences between the cardiovascular systems of the foetus and the newborn. In the foetus the major organ of exchange for gases, nutrients, and waste products is the placenta where large blood supplies, both maternal and foetal, come into close contact. Because the lungs are not functioning, with gas exchange occurring at the placenta, the foetal circulation is single rather than double (see figure 70).


a Examine figure 69. Which vessel carries the most highly oxygenated blood?

b In the adult the carotid arteries carry highly oxygenated blood towards the brain. Why would this appear to be impossible in the foetus?

In fact the foetal brain does receive well oxygenated blood because the blood returning from the placenta in the umbilical vein is preferentially channelled across the right atrium, through the foramen ovale and into the left side of the heart (see figure 69).

superior vena cava

foramen ovale

inferior vena cava

ductus venosus""

ductus arteriosus

pulmonary artery

left ventricle

right ventricle

aorta

umbilical vein

umbilical arteries

placenta

Figure 69The circulation of blood in the human foetus.

In order to achieve a single circulation the left and right sides of the heart, which are basically separate pumps, have to be temporarily connected in parallel. A large vessel, the ductus arteriosus, connects the two outputs of the heart, the aorta and pulmonary artery, while the connection between inputs called the foramen ovale is an opening between the left and right atria covered by a muscular flap (see figure 69). Little blood flows through the lungs; their blood vessels are constricted and the resistance to flow is high, so that most of the blood entering the left atrium comes from the right, through the foramen.

c Why is it essential that blood flow to the lungs is not stopped altogether during the development of the foetus?


At birth, this system must convert to the more familiar double circulation in which the left and right sides of the heart are connected in series (see figure 70) and therefore the potential oxygen saturation of arterial blood supplying the body is much higher. In achieving this change the placenta is removed from the circulation, and the blood flow to the lungs increases greatly as they inflate; the 'parallel' connections of the foramen ovale and ductus arteriosus close.

Usually, within a minute or so of the delivery of the baby, the drop in temperature and the mechanical stimuli cause the umbilical arteries to go into spasm. In this way the low-resistance placental circulation is cut off and the aortic blood pressure rises. In practice midwives and obstetricians do not entirely rely upon arterial spasm to prevent loss of blood from the umbilical cord, so a plastic clamp or band is placed around it before it is cut.

As the infant takes its first breaths, the pulmonary blood vessels dilate and the pulmonary arterial pressure falls. This results in part directly from the inflation of the lungs and in part from a change in circulating prostaglandin levels (see page 62) which is caused by the rise in blood p02 . As the pressure falls in the right side of the heart and rises in the left side, the blood pressure gradient across the foramen ovale reverses and its flap, like that of a letterbox, shuts. The ductus arteriosus also constricts, possibly as a result of a decrease in prostaglandin secretion by the ductus wall, caused by the raised blood p02 . After closure, the lumen of the duct becomes obliterated during the next week or so. All this is quite a lot to happen in a short time. What happens when these changes do not quite take place as they are expected to do?

(RV = right ventricle; LV = left ventricle;FO = foramen ovale; DA = ductus arteriosus)

pulmonary artery ~

RV

pulmonary artery

pulmonary vein~~

aorta

lungs

LV

before birth after birth Figure 70A schematic representation of the circulation before and after birth. The thickness of the vessels represents the amount of blood flowing through them.


Figure 71Traces recorded from a full term infant, whose mass was 4 kg, with persistent foetal circulation which responded dramatically to a tolazoline infusion. In the lower tracing, 'Pa O 2 ' is the mean p0 . of arterial blood. Pressure is now usually represented in kPa; 125mmHg = 17kPa. Note also that the arrowhead above this tracing indicates the point at which the percentage of oxygen in the inspired air was reduced from 90 to 80 per cent.Dr. B. D. Speidel, Southmead General Hospital, Bristol.

HEART RATE

Some problems associated with the cardiovascular adaptations Perhaps the most common problem met nowadays is failure of the ductus arteriosus to close or remain closed. This is particularly serious in premature babies who have respiratory problems, and is a result of a combination of factors: low arterial oxygen concentration; high pulmonary artery pressure; circulatory fluid overload.

The open ductus means that a lot more blood than usual flows through the lungs and this causes a number of difficulties - it puts an extra load on the heart, which may begin to fail; it stiffens the lungs, making them inflate much less readily than usual so that the baby has to work much harder to breathe; and it may deprive organs in the rest of the body of a fully adequate blood supply. Many of these open ductuses will close spontaneously given time, but a few require drugs to assist closure. These drugs inhibit the synthesis of the prostaglandins which help to keep the ductus open. The most common one is Indomethacin but even the ubiquitous Aspirin has been used with limited success. In a small number of cases where drugs fail, surgical treatment may be necessary to bring about closure.

Another failure of cardiovascular adaptation is called persistent foetal circulation. In this case the pulmonary blood vessels fail to dilate and the pulmonary arterial pressure remains higher than the pressure in the aorta. As a result the right ventricular and atrial pressures also remain high and blood flows from right to left across the ductus arteriosus and foramen ovale as in the foetus, and the baby remains blue after birth. It is often difficult to distinguish this condition from others where the heart or large blood vessels have not developed correctly and which sometimes also lead to the baby being blue. However persistent foetal circulation usually responds to high concentrations of inspired oxygen, to drugs which dilate the pulmonary vessels (tolazoline, for instance, as shown in figure 71 ), and to time, and the outlook is good.

aei4 I !Kf-T-wlsj

RESPIRATION

125,

mmhg

TOLAZOLINE 10 mg

1


Figure 72a A histological section through the lung of a newborn lamb. The lung is properlyexpanded and the alveoli are clearly visible. (x 170.)b A similar micrograph of the lung of a newborn lamb suffering from respiratorydistress syndrome. The lung has failed to expand and little oxygenation of the blood willbe possible, (x 170.)Photographs, Animal Diseases Research Association, Moredun Institute, Edinburgh.

The development of the gas exchange systemLet us now turn to the respiratory side of newborn physiology. Of all the systems of the body, the lungs have to make the most abrupt change at birth, from no function at all to something approaching 100 per cent. The lungs of the foetus are noi completely collapsed. The developing bronchial tree, and the alveoli, are filled by a fluid secreted by epithelial cells of the lungs. The foetus makes breathing movements from a very early stage in pregnancy and the combination of fluid production and foetal breathing seems to be important in making the lungs grow. At birth the fluid must be removed from the bronchial tree and replaced with gas before pulmonary function can become established. Some of the fluid is mechanically squeezed from the lungs as the thorax is compressed during the baby's passage through the birth canal, and this fluid escapes through the baby's mouth and nostrils. The remainder is absorbed from the lungs in the first hour of life into lymphatic channels and from there into the blood stream.

The normal infant breathes vigorously very shortly after birth, as a result of the drop in temperature, physical stimuli, and the asphyxia which follows the removal of the placenta. The baby may have to generate very large inspiratory pressures during these first breaths, to overcome the viscosity and surface tension of the fluid-filled alveoli. The effect of surface tension on alveolar expansion is analogous to blowing


Figure 73A baby receiving respiratorysupport.This infant, born 12 weeksprematurely, has respiratorydistress syndrome and is beingartificially ventilated through atube from the mouth into thetrachea. His arterial oxygen level ismonitored by the black electrodeon his back, while he receives fluidsand nutrients infused into a vein inhis right leg. The woollen cap,besides holding the tracheal tube inplace, also reduces heat loss fromhis head.Photograph, Department of MedicalIllustration, Southmead GeneralHospital, Bristol.

up a party balloon - it is the first few breaths which are the hardest, but as the balloon expands the tension decreases. To reduce this surface tension epithelial cells secrete an extremely thin layer of an agent known as surfactant, which coats the internal surface of the alveoli, reducing the surface tension markedly and enabling the pressure within the alveoli to remain relatively constant whatever their diameter.

What then can go wrong with breathing in a newborn baby ? One of the commonest conditions that doctors have to treat is known as respiratory distress syndrome. This condition is due to a lack of surfactant and the baby is unable to expand its lungs because of the high surface tension. (See figure 72.)

The production of surfactant increases during pregnancy, so the risks of this condition are increased in premature babies. These babies will become blue because pressure in the pulmonary artery remains high owing to the failure of the lungs to inflate properly. As a result of this high pressure, deoxygenated blood will cross the foramen ovale and ductus arteriosus from right to left as in persistent foetal circulation. Blood which does manage to flow through the lungs may be less than fully saturated since it will perfuse alveoli which are not completely expanded. The treatment is to give respiratory support, sometimes taking over breathing altogether by a tube passing into the trachea, until the baby's surfactant production has improved (seefigure 73 ). Attempts have been made to put artificial surfactant into the lungs, but so far, with no great success.

Delayed clearance of the foetal lung fluid can cause problems leading to a raised ventilation rate. This is particularly common in babies who have been born by surgical operation (Caesarian section) and have not therefore had any of the lung fluid squeezed out. Luckily this condition corrects itself within a day or so.

Haemoglobin and the foetusIn order to transfer oxygen across the placenta to the foetus, foetal blood must have a greater affinity for oxygen than the mother's blood. This is indeed the case and is largely due to the foetus having a different type of haemoglobin (see section 4.1). During the four to six months after birth the foetal haemoglobin is replaced by adult haemoglobin, improving the respiratory functions of the infant.


STUDY ITEM4.24 Foetal haemoglobin

Examine the dissociation curves for foetal and adult haemoglobin (figure 74). Bear in mind that the p02 of foetal tissues will be around 3 kPa, whereas that of adult tissues may be around 5 kPa.

a Show how the possession of foetal haemoglobin is vital to the survival of the foetus.

b Explain why it is necessary to replace foetal haemoglobin with adult D haemoglobin after birth.

100

80

60

40

20

0

foetal haemoglobin

4.3 Blood technology

The need for blood transfusions

Blood is clearly an absolutely vital component of a working human body, and yet, being a liquid tissue, it is fairly easily lost from the circulation as a result of injuries. It escapes also during major corrective surgery, and occasionally an individual may suffer from one of the diseases which reduce the body's ability to manufacture blood cells. Whatever the cause, if an individual suffers a substantial blood loss it is essential that the loss is made good.

4 6 8 10 12 14

P02 < kpa )

Figure 74The oxygen haemoglobin dissociation curves for foetal and adult blood.

Blood donation

It was not until 1900 that the ABO blood groups were first discovered and it was shown that some of them could be mixed together without ill effect whereas others could not. In early attempts at blood transfusion, however, the main problem was that blood clotted within ten minutes of collection. During the First World War this problem was overcome by adding sodium citrate to the blood and so, during the 1920s, voluntary donor panels were set up in Britain. However it took the Second World War to get the blood transfusion service properly established and by 1940 there were eight regional transfusion centres, and the National Blood Transfusion Service came into being in 1948. In 1984 there were twenty regional centres in the UK.

Any person in normal health between the ages of 18 and 65 may donate blood two or three times a year without adverse effect. Each regional centre has its panel of local donors who are called to attend donor sessions at four- or six-monthly intervals throughout the year. In 1980 two million donations were collected in the UK.

Before blood is issued to hospitals certain tests are performed on each unit. The ABO and Rhesus (Rh) types are checked to ensure that there have been no labelling errors and special tests are performed to make sure that the donation is not infected with hepatitis, cyto- megalovirus, or syphilis. (Figure 75.)

Where a donor is discovered to have a rare blood type, details are sent to the Blood Group Reference Laboratory in Oxford where a record is kept of all special donors. The details of these donors are sent at


Blood donor session

blood donationplus samples 1 and 2taken from the donor

Regional transfusion centre

apiisample

1

Bisample

2

v7 \^Jd group blood tested ;ked for infections

results collated by computer:

if results satisfactory

transfused into patient

after laboratory tests on patient's blood and a further one on donor's red cells hospital

blood bank

blood donation goes into blood bank ready for issue to hospital

Figure 75How blood for transfusion reaches a patient.

regular intervals to all transfusion centres. There are a few patients who require a blood type so rare that there may not be enough donors in their own country. For these exceptional cases the international panel of donors may be explored to find where there are healthy donors in other countries. Some 28 nations contribute details to this international panel.

Components of blood

In normal health the bone marrow and lymphoid tissue manufacture sufficient numbers and proportions of the various cellular components of blood (see figure 76) but in illness or injury this may not be the case. Not only may whole blood need to be given to a patient but one or more of its individual components may be needed. Various procedures may be employed on donated blood to prepare and to preserve for as long as possible healthy whole blood and a variety of concentrates.


whole blood donation

plasma

platelets, white blood cells

red cells

Ife: • :K|S

centrifugation

cellular elements plasma

platelet \ Concentrat s processed to make:white cell ' specific coagulation factors

albumin red cell concentrates immunoglobulins

human plasma protein fractionFigure 76The components of blood.

Storage of blood

A typical, 450-cm3 donation of blood consists essentially of 220 cm3 of red cells and 230cm 3 of plasma mixed with 63cm 3 of anticoagulant solution and is stored at a temperature between 2 and 6 °C that lowers the rate of metabolism of the cells and reduces their consumption of respiratory substrate. Three different anticoagulant solutions are currently used: acid-citrate-dextrose (ACD), citrate-phosphate-dex trose (CPD), and citrate-phosphate-dextrose-adenine (CPDA). The citrate acts as an anticoagulant by converting ionized calcium, which is necessary for normal blood coagulation, into insoluble calcium citrate. The dextrose is used as a substrate by the red cells to support their metabolism during storage. The other components (phosphate and adenine) are used to slow down the inevitable depletion of the ATP content of the red cells.

Red cells have a normal life span of 120 days in the circulation; however, when blood is stored at 4 °C there is a slow but progressive loss of viability. (The viability of white cells and platelets decreases rather faster, and within the first 24 hours of storage there are noticeable decreases in the functional activity of these cells.) In the body ATP helps to regulate glucose metabolism of the red cells and maintains the integrity of the red cell membranes whilst DPG, as was mentioned earlier in this chapter, regulates the binding of oxygen within the cells. The concentration of both of these compounds falls during storage, with the result that the cells, when transfused, are susceptible to destruction because they are not able to function efficiently. Just over 50 per cent of red cells stored in ACD or CPD for 30 days would be destroyed within 24 hours of being transfused into a patient. A minimum requirement for stored blood is that it must allow at least 70 per cent survival of transfused cells after transfusion. These conditions are satisfied when blood is stored in ACD or CPD for 21 days and no longer. CPDA allows storage for up to 35 days because the extra phosphate and adenine help to maintain the red cell content of ATP and DPG.


When stored cells are transfused the lost DPG is fairly quickly regenerated and normal dissociation curves are obtained by between 16 to 24 hours after the transfusion. This loss of function has little clinical significance unless the patient has lost a massive amount of blood or unless there is a pre-existing heart or lung condition that interferes with oxygen delivery. In such cases blood of no more than ten days' storage is usually selected for replacement transfusion.

Using special freezing techniques red cells may be stored in liquid nitrogen for years. They are treated with glycerol (propane-1,2,3-triol) to protect them and then frozen. Such units may be quickly thawed after removal of the glycerol by washing and the red cells are then resuspended in plasma or in saline. Frozen red cell banks are most useful for the establishment of longterm depots of red cells of rare types.

Figure 77A single pack.

Preparation of the blood components

The technique of preparing most blood components has been made relatively easy by the use of the sterile plastic packs into which the blood is collected. Approximately 40 per cent of all blood transfusions will use whole blood, for which the donation is collected into a single pack and no further processing or centrifugation takes place (figure 77). About 60 per cent of donations are collected either into a double pack or a triple pack (figure 78).

Figure 78A triple pack ready for use.Photographs, National Blood Transfusion Service.

Blood that will be used to produce concentrated red cells and plasma is collected into a double pack. After collection into the primary pack containing the anticoagulant, it is centrifuged to throw the cells to the bottom part of the pack. Approximately 200cm 3 of the supernatant plasma are then expressed into the satellite pack which is disconnected and immediately frozen and stored.


Platelet concentrates are prepared, using a triple pack. The donation is collected into the principal pack which is lightly centrifuged leaving the platelets suspended in the supernatant plasma. 200cm 3 of this plasma are then expressed into the first satellite pack and the principal unit, containing the concentrated cells, is disconnected. The remaining packs are centrifuged at high speed to concentrate the platelets, after which 150 cm 3 of the supernatant plasma are expressed into the remain ing empty pack, which is also frozen and stored. The platelets are stored at 22 °C and have a shelf life of no more than five days.

Use of the components

Whole blood is used to restore blood volume where there has been excessive blood loss. The blood volume in an adult is approximately 5 dm 3 . If more than 1 dm 3 is lost then it must be replaced by whole blood. Whole blood is also used in open heart surgery and for other operative procedures where it is expected that there will be blood loss in the order of 1 dm 3 or more.

Red cell concentrates can be safely used for most transfusions where red cells are required and their use is gradually superseding that of whole blood. Such concentrates may be used in conditions where the bone marrow fails to function properly, as in leukaemia, with the result that the patient becomes anaemic. Such patients require red cells to raise their haemoglobin levels but they do not want the extra volume of the donor plasma.

Platelets normally survive in the circulation for nine days and are necessary for normal coagulation. When separated from freshly donated blood, however, they only retain their functional activity for five days. Platelet transfusions are used mainly in the treatment of malignant diseases such as leukaemia, where replacement of the bone marrow by abnormal cells grossly impairs platelet production.

White cell concentrates contain the white cell layers from ten or more units of freshly donated blood. Transfusions of these cells are used to treat patients with very low white cell counts, who also have severe bacterial infections that are not responding to antibiotics.

Fresh whole plasma, after being separated from the blood donation, is stored at — 30 °C or below. It contains clotting factors, fibrinogen, albumin, immunoglobulins, and other proteins, and is used primarily as the source material for the production of these factors. However, when it is thawed out at 37 °C and immediately transfused it is invaluable in helping to control bleeding in patients who lack more than one clotting factor.

Specific clotting factors. There are at least twelve of these, many of them being made in the liver, and, in addition to platelets and calcium ions they are essential for normal blood coagulation. (See figure 79.) There are some hereditary bleeding diseases, such as haemophilia, which are caused by a deficiency of one of these factors. Each of them may be prepared by fractionating multiple pooled donations of fresh plasma and can be used to treat patients with these disorders.

Human plasma protein fraction is an end product of fractionation and


blood and tissue coagulation factorsplatelets calcium

become 'activated'and convert • ' ' . ' ! "

prothrombin —————————+• thrombin

> which acts on .

fibrinogen

to create

fibrin clot

Figure 79A simplified diagram of blood coagulation.

consists of approximately 5 grams of albumin per 100 cm 3 . Its main use is in the emergency treatment of sudden, severe blood loss, where it is transfused to maintain blood volume until whole blood is available. It is also used in cases of severe burns to replace the fluid that is lost as a result of damage to the skin. (This product has now replaced dried plasma, which is no longer used.)

Albumin. Concentrated solutions can be prepared from pooled plasma donations and are used to treat conditions where the blood albumin level is low. Albumin is vital in maintaining the correct water balance of the tissues by its substantial contribution to the low water potential of blood.

Monoclonal antibodies

At first, most antibodies used were either obtained from a special panel of blood donors who had themselves developed specific or multi-specific antibodies after receiving a blood transfusion, or from animals which had been immunized against specific human blood group antigens. Immunologists are now able to generate cell lines that can secrete very specific (monoclonal) antibodies. A mouse is immunized with an antigen and the antigen-sensitized lymphoid cells are removed from the spleen of the mouse and fused with cells from a mouse bone marrow tumour to form hybrid cells. These cells will grow continuously in culture and secrete antibodies specific for the antigen with which the animal was immunized. A clone of cells derived from the fusion of one antibody-forming cell with one tumour cell is called a hybridoma. By means of this new technique, it may be possible to produce unlimited amounts of both common and rare antibodies that can be used not only for laboratory purposes but also for treating disease.


Transfusion

Human red cells carry many inheritable blood group antigens (for example, ABO, MN, Rh). Fortunately, in the majority of instances, only the ABO and Rh antigens are of primary importance during transfusion. Apart from the naturally occurring anti-A or anti-B antibodies, those corresponding to other red cell antigens are not normally present, although they may develop following a transfusion. Before a patient receives a transfusion of blood, tests are carried out to ensure that no abnormal antibodies against red cell antigens are present. A patient is transfused with blood of the same ABO and Rh group as his own and specialized tests are performed to ensure that the donation will be compatible.

A patient may die as a result of receiving blood of the wrong group. If blood is transfused too quickly or in too great a volume it may overload the circulation (particularly in the young and the elderly) and give rise to acute heart failure. Patients who receive regular transfusions may develop antibodies against donors' white cells and/or platelets and very occasionally produce antibodies against proteins in the blood. When these situations arise it is necessary to filter out white cells and platelets from the donation or to wash the red cells in solutions to remove the plasma completely.

The rhesus blood group system

Rhesus antigens are only present on red cells and are well developed before birth. For practical purposes blood is called rhesus positive (Rh + ) if the red cells contain the so-called D antigen, and rhesus negative (Rh —) if they do not. If an Rh — mother is carrying a baby whose red cells contain the D antigen it is possible that she may develop rhesus antibodies (anti-D) if her baby's blood enters her circulation during pregnancy or at the time of delivery. At a subsequent pregnancy these antibodies may begin to destroy her developing baby's Rh + red cells since the antibody can cross her placental barrier and enter the baby's circulation. The result of this is that the baby could become anaemic or even die in the uterus. This particular anaemia is called haemolytic disease of the newborn. It can now be almost completely prevented by administering anti-D immunoglobulin to all Rh — mothers who give birth to Rh+ babies, shortly after delivery. The immuno globulin destroys the Rh + red cells before they have time to stimulate an antibody response in the mother.

Summary

Most bloods which transport oxygen are found to contain a pigment which enables them to carry more oxygen than water would (4.1). Haemoglobin, the pigment in mammalian blood, is a complex protein and it is the structure of the pigment molecule which largely deter mines how much oxygen it can transport and how efficiently it does so (4.11).It is important that oxygen can be absorbed at the lungs easily and released to the tissues readily (4.11).


4 The dissociation curve of haemoglobin demonstrates its ability to function as a temporary oxygen carrier (4.13).

5 The shape and form of dissociation curves enable us to predict the affinity of the pigments for oxygen (4.13).

6 Humans put themselves into positions, activities, or locations inwhich oxygen is in short supply; the body is able to adapt to meet the new demands quite readily although there are limits to the extent to which changes are tolerated (4.2).

7 Training is aimed at making the maximum use of the oxygen that the athlete can obtain, and obtaining as much as possible during his or her event (4.21).

8 Animals that dive can use anaerobic respiration and a series ofcirculatory adjustments enabling them to make prolonged dives (4.23).

9 Under many circumstances diving animals are aerobic and do not use these modifications (4.23).

10 The problem associated with high altitude breathing is not the actual lack of oxygen but its limited availability; this is due to low atmospheric pressure (4.2).

11 There are many adaptations, both temporary and permanent, enabling humans to work at high altitudes (4.2).

12 The newborn child experiences oxygen lack because of the immaturity of its vascular and respiratory systems (4.2).

13 Modifications to the circulation occur shortly after birth; failure of these changes can lead to very severe problems of oxygen supply to the tissues (4.2).

14 Problems of this sort can often be helped by intensive care by specialized medical teams and equipment (4.2).

15 Blood is such a vital tissue and such a manoeuvrable one that it is relatively easily lost, fairly simply regained, and needed frequently in operations and in treatment of accident victims (4.3).

16 A sophisticated technology has sprung up around blood, enabling transfusion to be safely carried out (4.3).

17 A number of the many components of blood may be separated from the whole fluid, so that one donation may aid more than one patient (4.3).


HARRISON, R, J. and KOOYMAN, G. L. Carolina Biology Readers No.6, Diving in marine mammals, 2nd edn. Carolina Biological SupplyCompany, distributed by Packard Publishing Ltd., 1982.HEATH, D. and WILLIAMS, D. R. Studies in Biology No. 112, Life athigh altitude. Edward Arnold, 1979. (A thorough account of all theadaptations to life at altitude.)HEMPLEMAN, H. V. and LOCKWOOD, A. P. M., Studies in Biology No.99, The physiology of diving in man and other animals. Edward Arnold,1978.ROBERTS, M. B. V. Biology. A functional approach. Nelson, 1982.


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