contours of breathing - gas transport - ers-education

Contours of Breathing - Gas Transport

G.J. Tammeling and Ph.H. Quanjer

respiratory function expert; but the expert in respiratory physiology is concerned with the normal. The author himself has recently twice undergone a very sophisticated investigation of respiratory function in Australia and in the United States. It struck him, and distressed him also, that the re-sults were to be used to supplement the limited series of ‘normal test subjects’, despite his insisting that this classification was at the very least open to serious doubt. Thus much of the benefit which has been achieved by further refined techniques is lost again in the haphazard sampling of the very important reference data. It is therefore gratifying that the authors are specialized respiratory phys-iologists, and good teachers, and that they also have a long and extensive clinical experience behind them. The contribution of theory and research to clinical practice receives a fresh impetus from this work, which originates from Leiden where Boerhaave carried out his pioneering work.

This is a word of guidance along the reader’s journey. This journey may sometimes be long, and how the book is received will depend on its appearance and on its character. A book’s appearance is judged on ‘love at first sight’ and there is no reason to doubt the success of this book on that score. Knowing the authors there is also every reason to anticipate that the character of the book will be good. The journey will thus go well, and the book should be well received. Boehringer Ingelheim B.V. will not be sorry that they have organized this journey so generously.

N. G. M. Orie, Groningen, August 1978

Preface

Monsieur Jourdain in Molière’s “Le Bourgeois Gentilhomme” was amazed to learn that he had been speaking prose without knowing it for forty years. He might have

been upset therefore to be told that he was a mammal, and greatly astonished if he had known that when breathing he was making unconscious use of a highly developed physi-ological system. There is no doubt that this complex but necessary part of our autonomic system is highly developed. It is therefore important that the different aspects of normal and pathological energy transport, its regulation and the function of the lungs and the airways should be described in accordance with recent views.

This is achieved extremely well in the atlas written by my friends and former collabora-tors Tammeling and Quanjer, even if this book is not all light reading, but anybody who is studying a certain aspect of the physico-chemical events occurring during breathing, and who wishes to set them against the background of macro- and micro-anatomy of the lung will find the important points briefly, succinctly described and nicely illustrated in this first part of “Contours of Breathing”.

For the many people who wish to look again at the finer points of a certain facet, be it the analysis of a difficult respiratory problem, or the design of an experiment in pulmonary physiology, this book is a welcome asset. Workers in the basic sciences such as anatomy, histology and pharmacology, and in the clinical specialties including pediatrics, anes-thesia and cardiology will find that this book gives them a sound and reliable basis for their clinical and experimental problems. This book will also be helpful to technicians in clinical physiology laboratories.

The book provides a good example for the present day student, who is beginning his clinical studies, of how his theoretical knowledge can be integrated with clinical expe-rience. When he goes into practice, it will remain a useful reference work. For the older doctor reading the whole book would make too heavy demands on his time, and he should restrict himself to the parts which are appropriate to his knowledge and interest.

But there is more to it. Respiratory physiology, a laboratory science, subserves the whole clinical practice of respiratory diseases. It developed early and advanced rapidly in the 40’s and 50’s, but the fruits of this development have not yet all been gathered. It is clear that clinical practice often lagged considerably behind this rapid development. The tech-nical, physical and physiological aspects of lung function were often studied very thor-oughly, and could usually be accepted by the clinician as they stood. But the conclusions often did not tally with a much too limited analysis of the indices investigated.

For the patient with, say, asthma or bronchitis this can be attributed only partially to the



The initiative for the production of this volume came from Mr. J. Siebelink. Production and coor-dination were under the care of Mr. A. E. J. W. van der Vegte; the illustrations were produced by Studio Rastorfer (Munich), and the manuscript was prepared with the assistance of Mrs. G. Sand-wijk-Stuart and Mr. H. H. v. d. Meij. The authors have also taken advantage of the literature review service of the Netherlands Asthma Foundation. The authors would value any comments passed on by readers.

Leiden, April 1978.

G. J. Tammeling and Philip H. Quanjer

Aim high in hope and work,Let your watchword be order,And your beacon beauty.

D.H. Durnham (1846-1912)

Introduction

Disorders of the respiratory organs are among the commonest diseases in the West-ern World and have enormous social significance. Many doctors are confronted

with pathophysiology of the respiratory system every day. The field therefore requires considerable attention during both undergraduate and postgraduate medical training. Unfortunately, many students regard respiratory physiology as one of the most difficult parts of the medical course. Much the same is true of the general practitioner and the specialist, who has to delegate lung function tests to experts with specific physiological and technical skill. One must take into account, when imparting knowledge about the normal physiology and pathophysiology of respiration, that doctors and students vary enormously in the breadth and depth of their knowledge and experience. The doctor with many years’ experience, whose training lies in the dim and distant past, differs from his colleague whose knowledge extends deeper than his practical daily routine. They differ not only in the depth and content of their knowledge but also in their mental adaptation to new concepts.

“Contours of breathing” is based on a series of lectures on respiratory physiology for second-year medical students. The material has been supplemented on the basis of experience gained in different teaching situations relative to clinical application of lung function tests. Internationally accepted views, development and agreed concepts may be found together with personal findings and ideas. The publication is an arrangement of illustrations with corresponding short texts.The degree of difficulty varies from one illustration to another, depending on the topic. The reader should select what interests him at his own level of knowledge. This is facil-itated by the fact that most illustrations and their corresponding texts can be consulted separately. Abbreviations, terms, definitions, and basic concepts are explained in the appendix.

The present volume is confined to gas transport; form and function; volume and ventila-tory capacity; volume flow, and lung mechanics. The second volume deals with alveolar ventilation, gas exchange, diffusion, ventilation/perfusion, blood gases, acid-base balance and regulation of breathing.



1.1 Energy transport, signal transfer and regulation

In physiology, and in particular in clinical investigations of function, attention is paid to biological systems and tissues, their function in organs, the place of these organs in

the individual organism, and the interaction of the individual with its environment. The cell, the tissue, the organ, the organism and the environment are concentric structures in which life manifests itself. Energy transport, signal transfer and regulation are the pro-cesses which make life possible. Characteristic of all living organisms is that they grow, feed, develop, reproduce and - finally - die. They react in appropriate ways to changes in the environment, and may be able to stay alive in widely differing circumstances by maintaining the stability of its internal environment (homeostasis: Claude Bernard, see Cannon). The highly evolved organism can maintain the stability of its internal environ-ment by the use of regulating mechanisms. Acid production in the human body amounts to the equivalent of at least 10 litres of a normal solution of acid per day. This production is subject to marked and fairly rapid variations. Despite this, the pH is maintained within very narrow limits (7.36-7.45). The production of heat by the body at rest can vary be-tween 70 and 140 Watts (1-2 kcal. per minute), but despite this fact the body temperature remains within 0.5°C of the normal value. The body has enormous reserves available for homeostasis, and provision is made for functional failure by the pairing of a number of organs. As far as reserves are concerned a distinction is made between depots (e. g. the storage of energy in the form of fat) and functional reserves (e. g. maximum ventilatory capacity being some 20 times that of resting value). The organism is capable of adapting itself to its surroundings. The level at which homeostasis is regulated depends on exter-nal factors. The homeostasis of people living in high mountainous areas differs from that of those living at sea level. The homeostasis of people living in the Arctic is not the same as in those who live in the desert. Adaptation to the different environments has been termed heterostasis (Kao).

References:Cannon WB. The wisdom of the body. Norton and Co., New York, 1932.Kao FF. An introduction to respiratory physiology. Excerpta Medica, Amsterdam, 1972.



1.2 Phylogeny and ontogeny of the gas exchange system

The embryological development of the respiratory organs gave rise in the 19th centu-ry to the hypothesis that the development of the individual (ontogeny) recapitulated

that of the species (phylogeny): respiration in a fluid medium gives place to respiration in air. During phylogeny, parts of the respiratory apparatus maintained their function in a modified form (e. g. the pharynx) whereas others acquired a different respiratory or non-respiratory function. Thus, the sphincter of the swim bladder became the larynx while parts of the gills developed into the external auditory meatus. At the same time the functions of the respiratory system were expanded, e.g. by the inclusion of the olfacto-ry system. One essential aspect of the respiratory organs did not change, however: gas exchange continued to occur across a moist epithelial surface.

Phylogeny In monocellular organisms the cellular fluid is in direct contact with the external envi-ronment and gas exchange can occur directly through the membrane. In large multi-cellular organisms the distance between the cell and the external gas exchange system is bridged by a circulatory system. Depending on the external environment, the gas exchange system may be the body surface, gills or lungs. In some organisms, more than one organ is involved in external gas exchange, such as the skin, lungs, or gills and skin together.

Ontogeny In the first phase of embryonic development, gas exchange occurs in the trophoblast, which is embedded in the maternal tissue and supplied by the mother’s circulatory system. Later, blood islets are formed in the extra-embryonic mesenchyme, in which a lumen lined by endothelial cells forms. The extra-embryonic vessels invade the embryo and make contact with the embryonic blood vessels. The extra-embryonic vessels in the villi are also in contact with the maternal blood in the intervillous spaces. In this way a placental fluid/maternal fluid gas exchange system is formed. At birth, this changes to gas-fluid exchange in the lungs.

References Crelin ES. Development of the respiratory system: CIBA Clinical Symposia: 22, no 4, 1975.Langman J. Medical embryology, The Williams and Wilkins Company, Baltimore, 1966 Rahn H.

In: ‘Development of the lung’ (Ed: de Reuck A.V.S., Porter R.); CIBA-Symposium, Churchill, London, 1967.



References Hughes GM. In: ‘Development of the lung’ (Ed. de Reuck AVS, Porter R). CIBA Symposium; Churchill, Lon-

don, 1967.

1.3 Water and air breathing

Comparative physiology provides insights into the phylogenetic development of organs and organ systems. Comparisons of systems of gas exchange (external respiration) in various existing species (fish, amphibia and land animals) illustrates the phylogenetic development of the respiratory organs of vertebrates at the time of transition from life in water to life on land.

Anabas, the lungfish, and the Amphibia can be seen as representing intermediate stages in the gas exchange. Anabas is a fish which lives in water poor in oxygen, which periodically surfaces to take up an air bubble for transfer into an organ evolved for this purpose. Such air bubbles are necessary for the provision of oxygen. The gills are poorly developed and are mainly used for the excretion of carbon dioxide.

The lungfish gulps in air and passes the gas to a diverticulum of the pharynx which is a homologue of the lung, and from which oxygen is taken up. The poorly developed gills serve for external gas exchange of carbon dioxide.

In the amphibians, carbon dioxide excretion occurs mainly through the skin. The moist skin is the only organ which can function for this purpose, whether in water or in air. The skin takes over this function from the gills.

Desiccation is a great threat to carbon dioxide excretion. Excretion is promoted by an increase in the carbon dioxide gradient across the skin, i.e. an increase in the carbon dioxide concentration in the organism. Adaptation to a higher carbon dioxide tension is accompanied by a number of necessary conditions:(a) reduction of the carbon dioxide effect on the oxyhaemoglobin dissociation curve;(b) improvement of the buffering capacity of the blood, and(c) reduced sensitivity to carbon dioxide by the respiratory centres.

In terrestrial animals the entire process of external gaseous exchange occurs in the lung.

At the time of transition from life in water to life on land, first provision had to be made for an organ adapted to oxygen uptake (in Anabas and in the lungfish), probably be-cause the gill is better adapted to the exchange of carbon dioxide than of oxygen. In the second instance, provision had to be made for the excretion of carbon dioxide: respira-tion through the skin is a transitional stage.



1.4 Gas transport between air and tissue

In gas transport between the atmosphere and the tissue, ventilation and cir cu lation (active processes) are coupled in series with diffusion across the alveolar-capillary

membrane and in the tissues (passive processes). The transport capacity of the blood plays an important part in all this. The extent of gas transport (i.e. the number of litres of oxygen and carbon dioxide per unit time) depends on the tissue metabolism. The level of gas tension at which transport occurs is determined by the level of ventilation and circu-lation, by diffusion in the alveolar-capillary membrane and tissues, and by the transport capacity of the blood.

OxygenThe total capacity of oxygen in the adult human body amounts to about 1.5 L (68 mmol). The most important component is represented by the oxygen bound to haemoglobin, followed by oxygen in the alveolar gas. The oxygen bound to myoglobin is difficult to cal-culate and has no general function. At rest, oxygen consumption amounts to about 0.25 L/min (11 mmol/min). Thus about a sixth of the total quantity of oxygen present in the body is used per minute. This means that oxygen reserves are small relative to demand, i.e. that absence of oxygen can only be tolerated for a very short time.

A fortiori, this also applies during work, when oxygen consumption per minute is great-er than the total available oxygen in the organism. Anaerobic energy exchange cannot immediately compensate for an oxygen deficit and can only do so to a limited extent and for a short period. Aerobic tissue metabolism occurs under very low oxygen tension (see here). This is possibly connected with the phylogeny of cellular metabolism. Oxygen transport in biologically useful quantities can only occur at very high oxygen gradients because the solubility of oxygen in fluids is relatively low.

Carbon dioxideThe total quantity of carbon dioxide in the adult human body is about 6.2 L (279 mmol). The most important storage sites are the tissues and the blood. Carbon dioxide produc-tion at rest amounts to about 0.20 L/min (9 mmol/min). The output per minute thus amounts to about a thirtieth of the total storage capacity. The relationship between trans-port and storage is thus much less critical for carbon dioxide than it is for oxygen.

A marked increase in the total quantity of carbon dioxide can be tolerated quite well if it builds up slowly and the pH is maintained within narrow limits by means of the body’s compensation mechanisms. The difference in partial pressure of carbon dioxide between the tissues and the alveolar space is small. Despite this a considerable quantity can be transported because carbon dioxide is very soluble in body fluids and is transported in chemically bound forms.



Ventilatory disturbance A disorder of ventilation causes a decrease in alveolar oxygen tension and thus a decrease in oxy-gen tension in the blood supplied to the tissues. The cause is usually:(a) hypoventilation as a result of a reduction of functioning lung tissue;(b) a disorder of breathing mechanics;(c) a disorder of regulation; or(d) an increase in the dead space ventilation.These disorders can be compensated by an increase in capillary tissue circulation, an increase in the haemoglobin content of the blood, and a change in oxygen affinity of the haemoglobin. The arteri-ovenous difference in oxygen tension is reduced by the compensatory mechanisms, and the oxygen gradient in the tissues remains relatively favourable. A ventilation disorder must be considerable in extent before symptoms of disordered metabolism become manifest.

1.5 Normal and abnormal oxygen gradient

Normal

The oxygen tension (see A.6) drops from 20 kPa (150 mm Hg) in the atmospheric air to less than 0.7 kPa (5 mm Hg) in the intracellular fluid. Four oxygen gradients can

be distinguished.

There is a steep oxygen gradient between the outer air and the alveolar space. This results from alveolar gas exchange (uptake of oxygen and release of carbonic acid) and the saturation of the alveolar gas with water vapour (BTPS). The gradient depends on the relation between alveolar ventilation and perfusion and is connected with the dead space ventilation. The alveolar oxygen tension varies slightly as a result of the respiratory movements. The mean alveolar oxygen tension is calculated indirectly from the simpli-fied alveolar gas equation: PA,O2 = PI,O2 - PA,CO2/Rin which PA,O2 = alveolar oxygen tension, PI,O2 = oxygen tension of the inspired gas, PA,CO2 = alveolar carbon dioxide tension, and R = the respiratory quotient.

The gradient between the alveolar oxygen tension and that in the blood in the pulmo-nary veins is small, and in normal circumstances is due to a slight shunt circulation and to regional differences in ventilation/perfusion relationships. The gradient increases as the mixed venous oxygen tension decreases due to a low cardiac output and/or haemo-globin concentration.

In normal circumstances the oxygen tension in the systemic arteries and arterioles is practically the same as that in the pulmonary veins; the oxygen tension remains high (12 kPa = 90 mmHg) almost until the cells which are to consume the oxygen are reached.

The oxygen gradient is greatest in the tissues, where metabolism takes place. This is the most difficult part of gas transport: diffusion into the extracellular and the intracellu-lar fluid. A reduction of oxygen tension in the external air has no significant effect on the in-tracellular oxygen tension as long as the ventilation and circulation can act as regulating processes to compensate for the change.



1.6 Abnormal oxygen gradient (continued)

Disturbance of alveolar gas exchange

A disorder of alveolar gas exchange will bring about an abnormally steep oxygen gradient between the gas in the alveoli and the blood in the pulmonary veins. The

following disorders will be considered:(a) regional differences in ventilation/perfusion relationships, of which the most ex-

treme example is a pulmonary shunt circulation and alveolar dead space ventilation and

(b) increased diffusion resistance in the alveolar-capillary membrane. In the first place these disorders are compensated as far as possible by an increase in alveolar ventilation, i.e. a reduction of the gradient between the atmosphere and the alveoli. Thereafter the compensation mechanisms are the same as those for a disorder of ventilation (see here):(a) an increase in tissue circulation;(b) an increase in the haemoglobin content of the blood, and(c) an alteration of the oxygen affinity of haemoglobin.

Disturbance of systemic circulationA central circulatory disorder accompanied by abnormal blood gas values is usually the result of an abnormal right-to-left shunt in the heart or great vessels, or of reduced cardiac output as a result of heart failure. The oxygen tension of the blood flowing to the tissues is abnormally low. Satisfactory tissue oxygenation is usually not initially achieved by an increase of ventilation but by increased circulation and by alteration of the trans-port properties of the blood. In some cases an increase in peripheral circulation is not possible, and the only possible compensation mechanism is a change in the transport properties of the blood.

A peripheral circulatory disorder with abnormal blood gas values occurs in reduction of the tissue circulation, either due to local causes such as vascular occlusion or stasis, or to a reduction of cardiac output. In this case the oxygen tension of the blood remains normal but the oxygen gradient in the tissues is steep because the relation between supply (blood circulation) and demand (metabolism) is unfavourable. The compensation mechanisms are limited to:(a) an increase in the oxygen capacity of the blood;(b) a reduction of the oxygen affinity of the haemoglobin and(c) an increase in arterial oxygen tension produced by increased ventilation. The latter is, however, of almost no practical significance. Disorders in the tissue oxygen gradient caused by abnormalities in the internal environment such as oedema are com-parable with disturbances in the peripheral circulation as far as internal gas exchange is concerned.



lated most closely with the properties of the enzyme systems involved. The chemical energy of ATP is used for different types of work, all depending on circumstances and type of cell: chemical, osmotic, electrical or mechanical work. These types of work subserve several types of activity in the living organism: cell renewal, cell growth, active transport, production of electrical potentials, mechanical work, and the production of heat.

References Guyton AC. Textbook of medical physiology: 4th ed. Saunders, Philadelphia, 1971.Kuyper ChMA. Natuur en techniek 1976; 44: 784, 1976 and 1977; 45: 22.

1.7 Metabolism and energetics

A highly complex, well-ordered structure comprising large quantities of molecules rich in energy must be maintained within the cell to ensure its continued existence.

The fabrication of such molecules requires a continual supply of energy. The energy released by the combustion of nutrients (glucose, amino acids and fatty acids) is stored in the form of high energy phosphate bonds. Adenosine triphosphate (ATP) contains two such bonds (at 37° C, 34 kJ (≈ 8 kcal) of available energy per bond). There are several stages in the energy-producing catabolic process. The first step for glucose is glycolysis. Under anaerobic conditions, two molecules of pyruvic acid are formed from one molecule of glucose. The energy released appears in the form of two molecules of ATP. Glycolysis is not an efficient system for energy production, since only 10 % of the chemical energy present in the glucose ‘molecule is released. Aerobic metabolism (oxidative phosphorylation) occurs in the mitochondria and produces much more energy than anaerobic metabolism or fermentation. The energy re-leased is also stored in the form of ATP. Two “active acetic acid” molecules (acetyl-CoA) come from each molecule of glucose, and acetyl acetic acid is formed from fatty acids and amino acids. The acetyl-CoA penetrates the mitochondria together with oxygen and is broken down in the Krebs’ (citric acid) cycle into hydrogen atoms and molecules of carbon dioxide. The carbon dioxide diffuses out of the mitochondria into the cytoplasm, and thence out of the cell. The hydrogen atoms combine with oxygen under the control of oxidative enzymes, and the energy released is used to form ATP from ADP and in-organic phosphate (the respiratory chain). Any material from which acetyl-CoA can be formed is suitable for aerobic metabolism. One glucose molecule produces two acetyl-CoA molecules, via pyruvic acid. One molecule of a fatty acid produces many molecules of acetyl-CoA by means of 13 oxidation, and thus produces many high energy phosphate bonds per molecule. Whenever the oxygen tension at the site of metabolism is above 0.7 kPa (5 mm Hg), oxygen is not an inhibiting factor and intracellular consumption of oxygen depends exclusively on the amount of ADP available. Oxygen consumption is also determined by the oxygen tension when the Po2is below 0.7 kPa (5 mmHg). In normal cir-cumstances the oxygen tension in the mitochondria is probably below 0.3 kPa (2 mmHg). The relationship between oxygen tension, ADP concentration and oxygen consumption is corre-



As the body temperature drops (hypothermia), ventilation must be so regulated that the carbon dioxide content of the blood is not changed, the intracellular pH remains close to neutral, and the dissociation of the protein buffer remains constant. This requires a reduction in arterial carbon dioxide tension, i. e. a relative increase in ventilation over metabolism. This is, however, a debatable point.

References Rahn H, Reeves RB, Howell BJ. Amer Rev Resp Dis 1975; 112: 165.Rahn H. Bull Europ Physiopath Resp 1976; 1: 5.Reeves RB. Proc Int Union Physiol Sc 1977; XII :93.

1.8 Maintenance of the acid-base state

Regulation of the acid-base state is essential for the functioning of the living organism. The intracellular pH is actively maintained around pH 7 (neutrality). At this point most metabolites are virtually completely ionized. Complete ionization is an efficient mecha-nism for maintaining the products of metabolism within a cell or organelle (Davis, see Rahn). The maintenance of the intracellular pH at around neutral is thus essential for metabolism.At a given temperature the ionic product of water is constant: [H+ · [OH-] = Kw. From this it follows that pKw = pH + pOH. In a neutral solution: [H+] = [OH-] and pH = pOH. Thus if the pH is neutral, pN = pH = pOH = 0.5 pKw. The pN depends on the temperature. As the temperature changes, the intracellular pH follows the change in pH at the neutrality of water. This implies that the pK of the intracellular buffer mechanism must follow the changes in the neutrality of water. Cellular and extracellular fluids contain three important buffer systems: protein, phosphate and CO2-bicarbonate. The systems are highly dependent on temperature, par-ticularly the protein buffer system (Reeves). In order to maintain intracellular neutrality, the pK of the protein buffer system must lie around neutrality and must change with temperature as the pH does at neutrality. The protein buffer which satisfies this demand is the imidazole group in histidine. With change in temperature, the extracellular pH alters parallel with the pH at neu-trality of water and the intracellular pH. The pH gradient between the extracellular and intracellular fluids is thus constant (temperature independent) and amounts to 0.7 pH units (K’). This indicates that the extracellular [H+] is five times less than the intracellular [H-]. This large H+ gradient is necessary for the removal of acid metabolites. Regulation of the extracellular pH is achieved by protein buffering (imidazole group), alveolar venti-lation (CO2) and renal excretion or retention (H+ or HCO3

-). In normal circumstances the body temperature varies from region to region. During work, the skin temperature falls to about 25°C and the muscle temperature can rise to 41°C, while the central temperature remains at about 37°C. As a result of the constant carbon dioxide content of the blood, the following alterations occur:Blood T pH PCO2 °C unit mm Hg kPaSkin 25 7.60 22 2.9Lung 37 7.40 40 5.3Muscle 41 7.35 48 6.4Since pH neutrality is highly dependent on temperature, the definition of acidosis and alkalosis is very difficult in such circumstances. The acid-base regulation is directed towards maintenance of the degree of activity of the protein buffer. This is an advantage to the organism because the distribution of ions and water remains constant, as does the store of carbon dioxide at varying temperatures.



1.9 Regulation of a biological system

Living organisms show a high degree of stability in changing surroundings and react appropriately to changes in the environment. This is made possible by the presence

of large numbers of regulatory processes. The condition under which a process occurs is influenced by internal and external factors (the internal and external environment). A regulatory system by means of which the condition of a biological process is held as far as possible at the reference point is called a homeostatic system (see here). An organ-ism must have a model of a process to be able to control that process and must test it against the process. The making of models is an essential property of the living organism (Verveen). A biological process is under the influence of a constant energy load (X1) and a disturbing energy flux (X2), as well as a corrective energy flux from a store (Y4). The resultant of these energy streams determines the actual regulated condition of the controlled process (Y1). This condition is observed by means of an organ, the sensor. The sensor transforms the condition of the process in a feed back signal to an organ (com-parator). This compares the signal with an independent commanding signal (X3) and delivers a controlling signal (Y3) to the effector. The effector is an organ which influenc-es the condition of the process by a change (in this case a correction) in the supply of energy from the store. The system has a ring structure. The pathway from the comparator is via the effector, which produces the required energy from the store, to the process. The condition of the process is relayed via the sensor to the comparator. It is thus a negative feed back system. When the feed back signal (Y2) corresponds with the commanding signal (X3), the process has reached the desired optimal condition.

An example is the biological process for maintaining the oxygen tension in the arterial blood; the constant load (X1) is the oxygen consumption in the tissues; irregularities in metabolism due to changing from resting conditions to work, or to alterations in the environmental temperature, are disturbances (X2). The condition of the process, i.e. the arterial oxygen tension, is observed by a chemoreceptor (the sensor). This transmits a signal to a comparator which compares this with a set point and relays a commanding signal (X3) to the effector. How the comparator and the set point for oxygen tension act, and where they are localized, are only partially known. The effector is the ventilation: the oxygen tension is adjusted by changes in ventilation. The process is, of course, much more complex. The arterial carbon dioxide tension (or pH) plays a part in addition to the arterial oxygen tension, whereas ventilation itself forms the subsidiary part of another regulatory system. In biology, systems are usually compound and many processes are regulated, often as a result of conflicting information inputs. Optimum conditions can-not be achieved, and the actual situation arrived at is usually a compromise.

ReferenceVerveen AA. Annals of System Research 1972; 2: 117.



1.10 Ventilatory regulation of oxygen transport

Gas transport between the atmosphere and the tissues comprises several different processes: ventilation, the transport of gases by the blood, circulation, and the diffu-

sion of gases into the lungs, blood, lymph and tissues. Regulation systems are necessary for the mutual adjustment of these processes and for their adaptation to the internal en-vironment. The optimal conditions for the body cells are attuned to gas transport which is as efficient as possible. Gas transport can be regulated by alterations in gas tension in the blood (the effector is ventilation), in the transport properties of the blood (the oxygen binding capacity and the acid-base balance), and in the volume flow of the blood (the effector is the circulatory system). These effectors are themselves regulated processes which influence each other.

Only the ventilatory regulation of oxygen transport is discussed in greater detail below. This regulatory system includes at least two sorts of sensors: chemoreceptors and mech-anoreceptors. The sensors for the one process can be localized in another process, so that the regulatory system is very complex. A simplified example will now be given.

Internal gas exchange (metabolism) is the loading and disturbing factor in oxygen transport. From the point of view of regulation of the volume flow and the transport properties of blood, the extent of oxygen transport is determined by the oxygen tension in the arterial blood. The arterial oxygen tension, i.e. the condition of the process YA,1, is monitored by a sensor (chemoreceptor). This transmits a feed back signal (YA,2) to the comparator A which compares the signal with a commanding signal from set point A (XA,2) and relays a controlling signal (YA,3) to the effector (the ventilator, i.e. the lungs). The activity of the ventilator is so adjusted that the regulated gas tension corresponds with the set point. Ventilation itself is also a process requiring regulation.

The ventilatory status (YB,1) is monitored by sensors in the respiratory organs (mech-anoreceptors, stretch receptors and baroreceptors) which send a signal (YB,2) to the comparator B which compares it with the set point (XB,2) and relays a signal (YB,3) to the effector, i.e. the respiratory muscles. The final, regulated condition of the arterial gas tension (YA,1) thus depends on two relayed signals: YA,3 and YB,3. There may be an interaction between the set points A and B. The regulating system of oxygen transport is thus very complicated even if the circulation and transport properties of the blood are not taken into account, nor the fact that chemoreception is a compound process to which the carbon dioxide concentration and pH contribute as well as the partial pressure of oxygen.

Reference Kao FF. An introduction to respiratory physiology. Excerpta Medica, Amsterdam, 1972 .Verveen AA. Annals of Systems Research 1972; 2: 117.

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