sign in sign up
<<
Home , Circulatory system, Pulmonary circulation, Respiration (physiology)

Thorax 1994;49 Supplement:S5-S8 S5

Evolution and the : first published as 10.1136/thx.49.Suppl.S5 on 1 September 1994. Downloaded from

Peter Harris

We were sitting, I recall, in the canteen of the their characteristic colour, was chlorophyll. Medical School at Birmingham. It must have The problem for the rest of the inhabitants been 1958. I had just returned from a year and ofthe planet was that the new process ofenergy a half at the , New York, transformation had a highly toxic waste prod- my mind still reeling from the experience of uct. This was . Its is not due to working in the cardiopulmonary laboratory of the diatom of the molecule of oxygen, but Andre Cournand. Donald Heath had returned to other forms of oxygen known as oxygen free from the Mayo Clinic where he had coolly radicals. The free radicals are highly reactive reshaped the face of pulmonary vascular path- chemically and attack many organic molecules.' ology. And it was there, in the canteen, that They inactivate enzyme by oxidising we planned to write a book on the pulmonary their sulphydryl groups, and they destroy circulation. It was the beginning of a col- membranes by forming peroxides. laboration and friendship which was to last to The new photosynthetic process was highly this day and through which I came to ap- successful to the extent that the earth's at- preciate, among many other things, those ima- mosphere gradually accumulated oxygen. Such ginative intellectual processes whereby static pollution spelt death to most of the forms of anatomical images of dead under the life then existing, and the threat to the world microscope can be transfigured into dynamic community must have been immense. concepts of living pathological processes. Doubtless, through genetic processes they During the succeeding 30 years our mutual responded by developing mechanisms ofchem- interests led us on a series ofexpeditions to high ical defence. Some were simple intracellular altitudes which, in unexpected ways, added a compounds such as glutathione which could depth of understanding and insight into com- scavenge the free radicals. Others, such as mon diseases back home. We were concerned, superoxide dismutase, were enzymes. Even not with the short term problems of ac- today these defences are still protecting the climatisation encountered by the occasional cells in our bodies, preventing - for example - http://thorax.bmj.com/ visitor to the mountains, but with the evidence our adipose tissue from going rancid inside us. for genetic adaptation in populations of and animals that have, for generations, been fated to spend their entire lives there. Oxygen as fuel Such studies have, inevitably, prompted The of life is always opportunistic and, wider considerations of the way in which ge- at a certain point, some organisms learned how netic influences have fashioned the and, to use the properties of oxygen as an electron in the following review, I shall try to give a donor and proton acceptor and to harness its on September 25, 2021 by guest. Protected copyright. more general background ofthe ofthe reduction to the formation of ATP. An even lungs and to show how important evolutionary more astonishing step was the takeover by nuc- influences may be in understanding the pul- leated organisms of these oxygen utilising monary circulation. forms, which became incorporated in their cytoplasm as mitochondria where they have remained ever since. In this extraordinary way Pollution of the with oxygen oxygen changed from being a lethal pollutant Life on our planet began in an atmosphere ofthe atmosphere to become the element most devoid of oxygen. The first organisms derived generally essential to life on the planet. their from the breakdown of complex molecules which had been formed in the im- mense heat of the creation of the world. Some and convection of the primitive pathways of anaerobic meta- Life had its origin in , and the first cells bolism persist to this day in every cell of our floated freely in that medium which is essential bodies. to all living organisms. The cell wall was a It may be that the supply of such complex subtle compromise between the necessity to molecules became used up. Perhaps for this maintain a barrier which would protect an reason, or more probably out of random dis- identity and the necessity to import and export covery, about a billion and a half years ago a materials. Because of their minute size the group of microorganisms discovered a way of unicellular organisms were able to exchange producing biologically useful energy from the food and excrement directly across their sur- sunlight which fell unfiltered on the earth. face. The movement of such materials to and S Polo 2171, were the algae. The essential was 30125 Venice, These blue-green from the cell primarily by diffusion, al- Italy substance through which the conversion of en- though the random currents of the watery en- P Harris ergy could be effected, and which gave them vironment must also have provided a fortuitous S6 Hamis help. As multicellular organisms developed and of 90-150 ml/min/kg, while that of fishes3 is grew larger, however, simple diffusion became about 10-40 ml/min/kg. Thorax: first published as 10.1136/thx.49.Suppl.S5 on 1 September 1994. Downloaded from inadequate and they needed to impose their A visit to the local butchers and fishmongers own convective streams on the surrounding will illustrate the reason for the increase in water in order to maintain an adequate ex- oxygen consumption. Mammalian and avian change. Many simple organisms, such as the flesh is mostly red, while flesh is white. coelenterates and , use the surrounding The white of the fish derives water as their sole means of convective trans- its energy mainly from an anaerobic glycolytic , which serves the combined functions of breakdown, while the red skeletal muscle of ingestion, , and . the and is rich in mitochondria As animals grew ever larger and more com- and the carrier pigment which per- plex, an internal convective system mits an increased use of oxygen. Glycolysis can also became essential. The external convective provide energy only for short intense periods system was retained and, in primitive of activity. The great advantage of oxidative such as amphioxus or the , provides is that it permits the prolonged a means for filtering food at the same time activity that has made the warm blooded ani- as for respiratory exchange. Even in such an mals so dominating a force on the planet. advanced form of life as the the function of the external convective system is still mixed. The passage of water through the mouth is The cardiovascular system used for ingestion, while its movement across In the and molluscs the internal the serves to exchange, not only respiratory convective system is an open one. The cardiac gases, but also water and salts and ammonia, pump moves through the directly the chief end product of nitrogenous meta- into the intercellular spaces, whence it returns bolism. to the through ostia. In the The migration of the animals on to dry land the cardiovascular system has become - for the imposed great restrictions on the external con- most part - a closed one, the blood being vective system. In amphibia considerable ex- separated from the interstitial liquid by change of water, , urea, and respiratory . There are points in the circulation, gases could still take place across the moist however, where this separation is not complete . Exploration far from the water's edge - in the , , marrow, and renal glom- required an impervious skin and so those func- eruli. In addition the provides tions of the skin largely became discarded. a direct communication between the blood and Instead the skin took over the fuinction of re- the interstitial liquid. gulation of which was required The fish heart4 comprises a single by the evolution of warm blood. By now the and . The blood is expelled from the exchange of respiratory gases was restricted ventricle into the ventral , then passes http://thorax.bmj.com/ to the newly evolved lungs where a certain through the gills before reaching the dorsal obligatory loss of water and heat also took aorta. The supply of blood to the tissues is place, while the excretion of nitrogenous waste from the through a second was restricted to the kidneys. bed in series with the exchange capillaries of Motion of the body as a whole is also a form the gills. of external convection. The ambivalence of The heart is composed of two the function of movement is expressed at its atria and one ventricle. Systemic venous blood simplest in the Paramecium. Does it swim? Or returns to the right atrium, while blood from on September 25, 2021 by guest. Protected copyright. is it simply renewing the water around it? Many the primitive lungs passes to the left atrium. fish use swimming to force water across the The presence of a spiral in the conus gills and to trap food in the . The arteriosus and the positions of the atrio- movement of any predator is only an extension ventricular orifices are believed to direct most of the same principle. And we all walk away of the systemic return to the lungs, and most from our own excrement. In these ways move- of the pulmonary venous blood to the rest of ment of the body takes its place alongside the the body. other convective systems. In mammals and birds the systemic and pulmonary circulations have become com- pletely separated, apart from a minute com- Oxygen requirements munication through the bronchial circulation. The development of the warm blooded mam- mals and birds was accompanied by a tenfold increase in oxygen consumption. Such an in- Pulmonary and systemic crease was made possible by the new external convective medium. Oxygen is relatively The separation of the into insoluble in water (about 0 3ml/100ml/ two parts was accompanied by a striking differ- 100mmHg), and its abundance in air per- ence in the two arterial pressures. The reason mitted an impressive decrease in the volume for a high systemic arterial is usually of ventilation.2 On the other hand, the internal ascribed to the necessity of perfusing the head convective medium was not so substantially in the upright posture. Guyton,5 for instance, changed, so that the internal distribution of the states: "One ofthe obvious purposes ofpressure increased consumption of oxygen could be met control is to keep the pressure high enough so only by an increased . The car- that blood can flow to all tissues of the body diac output of most mammals is in the region even when some of the tissues are far above Evolution and the pulmonary circulation S7

the level of the heart. For instance, in giraffes it suffered from two weaknesses - a sus-

the is regulated to a ceptibility to obstruction of the airways and a Thorax: first published as 10.1136/thx.49.Suppl.S5 on 1 September 1994. Downloaded from level between 200 and 300 mm Hg; this much susceptibility to flooding. The first was inherent pressure is required to assure blood flow to the in the to-and-fro convectional system. Powerful top of the head. At the other extreme the reflex glossopharyngeal systems evolved to pro- regulated level of the arterial pressure in prim- tect the from inhaling obstructing itive fishes may be as low as 30 mm Hg; because material, while in the terminal airways an in- there are no hydrostatic gradients in fishes this genious feedback system controlled the per- is an adequate pressure to assure blood flow to fusion according to the alveolar all tissues." of oxygen and thus maintained ventilation:per- However, the arterial pressure of the turkey fusion ratios and the systemic arterial oxygen is as high as that of the ,6 and aortic saturation. The implications of this in the ad- rupture in turkeys is a common problem for aptation ofhumans and animals to high altitude breeders. And why is the of the are discussed by David Williams (pages S9- mouse as high as ours, or that of the sparrow S13). The second defect, a susceptibility to even higher? Or why does the seal need a blood flooding, was inherent in the new interface pressure four times as high as the dogfish? between air and water. Pulmonary oedema A survey of the arterial pressure throughout could never occur in the fish. It is one of the the vertebrates7 reveals that a high blood pres- prices of evolution. sure is a feature of the warm blooded animals. It arrived together with the separation of the circulation into two parts, and with the vastly Pulmonary oedema increased capacity for physical which I shall not discuss here the forms of pulmonary accompanied the use of oxygen by red muscle. oedema resulting from chemical attack of the The explanation for the high arterial pressure alveolar capillary wall except to note that, in of the warm blooded animals8 lies in the ca- many of these, free radicals of various origins pacity of the heart to increase its output during have been implicated. exercise. During maximal exercise there is a Oedema of haemodynamic origin depends massive vasodilatation of the vessels supplying on the pulmonary . The low the muscles, so that the total systemic resistance arterial pressure in the pulmonary circulation, is near the lowest anatomically possible. The together with the low arterial resistance and perfusing pressure during exercise is thus what relatively high venous pressure, allow a total it has to be in order to supply the muscles with drop in pressure across the lungs of only about blood. Even if the system had been set at a low 5 mm Hg. Undoubtedly this contributes to the resting pressure, the arterial pressure during constancy of the capillary pressure. The chief exercise would have to increase to ap- threats to the pulmonary capillary pressure proximately this level. In that case, at the mo- come from a displacement of blood from the http://thorax.bmj.com/ ment when the left ventricle had to increase its systemic to the pulmonary compartments, and output it would be subjected to a substantial an increase in total plasma volume. increase in . Experience from the iso- The pulmonary is only about lated heart shows how unadapted to this is the one tenth of the systemic blood volume. This myocardium.9 It seems that it proved most makes the pulmonary capillary pressure par- effective for the body to maintain a stable high ticularly sensitive to any disability of the left arterial pressure and to modulate the local ventricle. When the output of a ventricle is

supply of blood by variations in regional peri- reduced blood is transferred from the com- on September 25, 2021 by guest. Protected copyright. pheral resistance. partment upstream to the compartment down- stream. It is therefore easy to see how a small reduction in output of a damaged left ventricle Evolution of the could lead to sufficient blood being transferred The lung was the which evolved to meet from the systemic to the pulmonary com- the greatly increased requirements for oxygen partment to cause a substantial increase in derived from a new external convective pulmonary capillary pressure. (The same is not medium. It required the redesigning of both true of the right ventricle since the maximal internal and external convective systems. In- quantity of blood that could be shifted from ternally the circulation was divided into two the lungs into the systemic circuit is somewhat parts, which maintained the primitive low per- less than a pint, and the effect should not be fusion pressure in the lungs while increasing different from that of giving a person a "unit" greatly the perfusion pressure in the rest of of blood.) It is a matter of evolutionary mis- the body. Externally an elaborate system of fortune, therefore, that the left ventricle has to branching airways emerged from a single out- support an afterload much greater than does pouching of the pharyngeal ectoderm. The the right, and that the , sub- lightness of the air permitted a to-and-fro con- jected to an evolutionally imposed high pres- vectional motion instead ofthe continuous one- sure, are susceptible to . way flow across the gills. Separating the two To these possible effects of a damaged left systems was a vast and delicate exchange mem- ventricle are almost always added the effects brane less than 1 ,um thick. It was as big as a ofan increase in total blood volume. The reason squash court, and yet had been organised in a for this lies in the importance which the body space the size of a football, small enough not gives to the maintenance of the arterial pres- to be an encumbrance. sure."'°" Any threat to the arterial pressure The efficiency of the design is staggering, yet evokes a response ofthe sympathetic and : S8 Harris :aldosterone systems which sustain and flooding which are of everyday concern in

the arterial pressure at the expense of an ex- the wards. Thorax: first published as 10.1136/thx.49.Suppl.S5 on 1 September 1994. Downloaded from pansion of the blood volume and retention of 1 Loesser KE, Kukreja RC, Kazziha SY, Jesse RL, Hess ML. salt and water.21-14 Oxidative damage to the myocardium: a fundamental mechanism of myocardial injury. Cardioscience 1991;2: 199-216. 2 Dejours P. Principles of comparative respiratory . Amsterdam: North-Holland, 1975. Conclusions 3 Johansen K. Comparative physiology: and The pulmonary circulation is the meeting place circulation in fishes. Ann Rev Physiol 1971;33:569-612. 4 Satchell GH. Circulation in fishes. Cambridge: Cambridge of two great convectional transport systems. University Press, 1971. How it came to be as it is can be elucidated 5 Guyton AC. The relationship of cardiac output and arterial pressure control. Circulation 1981;64: 1079-88. by considerations of evolutionary necessities. 6 Gresham GA, Howard AN, Jennings IW. Dietary and First among these is the development of an in the turkey. Jf Pathol Bacteriol 1963;85: 291-8. increasing need for oxygen in the evolving spe- 7 Altman PL, Dittmer DS, eds. Biological handbooks: respiration cies. Second is the emergence from the andcirculation. Bethesda: Federation ofAmerican Societies for Experimental Biology, 1973. and the exploration of dry land. The physical 8 Harris P. Evolution and the cardiac patient. Cardiovasc Res two convectional systems 1983;17:373-8. requirements of the 9 Elzinga G, Westerhof N. How to quantify pump function have necessitated compromises. On the cardio- of the heart. Circ Res 1979;44:303-8. 10 Harris P. Congestive cardiac failure: central role of the vascular side has come a dependence on a high pressure. Br Heart J 1987;58:190-203. arterial pressure, fiercely defended by ne- 11 Harris P. Role of arterial pressure in the oedema of heart disease. Lancet 1988;i:1036-8. urohumoral mechanisms at the expense of a 12 Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole-Wilson PA, retention of water and salt. On the external Harris P. of cardiac origin. Circulation 1989;80: 299-305. side has been the need for a large exchange 13 Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole-Wilson PA, combined with the convenience of Harris P. Pathogenesis of edema in constrictive peri- interface, carditis. Circulation 1991 ;83: 1880-7. an organ of limited dimensions. The system of 14 Anand IS, Chandrashekhar Y, Ferrari R, Sarina R, Guleria R, Jindal SK, et al. Pathogenesis of congestive state in to-and-fro ventilation into a blind tree of air- chronic obstructive pulmonary disease. Circulation 1992; ways carries with it the twin perils of blockage 86:12-21. http://thorax.bmj.com/ on September 25, 2021 by guest. Protected copyright.