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We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.
The pulmonary circulation conveys the entire output of the right ventricle via the pulmonary arteries to the alveolar capillaries and returns the blood, via the pulmonary veins, to the left atrium. The lung has a second, though far smaller, circulation, the bronchial circulation. This arises from the thoracic aorta, supplies systemic arterial blood to the lung, has some interconnections (anastomoses) with the pulmonary microcirculation and drains into the systemic venous system.
The pulmonary circulation differs from the systemic circulation in several important respects. For example, it is a low-pressure, low-resistance system; the time-average excess pressure in the pulmonary arteries is only about 2 × 103 Nm−2 (15mm Hg or 20cm H2O), or approximately one-sixth of that in the systemic arteries, while the total blood flow rate through the lungs is the same as that through the systemic circulation. Further differences are that the pulmonary arteries have much thinner walls than the systemic arteries, and the pulmonary vascular bed is apparently not regionally specialized. In addition, vasomotor control in the pulmonary vessels is believed to be relatively unimportant under normal conditions; unlike the systemic arteries and veins, the vessels do not undergo large active changes in their dimensions.
The main function of the lungs is the exchange of oxygen and carbon dioxide between the air and the blood. However, any gas for which there is a difference in partial pressure between pulmonary capillary blood and alveolar gas will diffuse across the alveolar capillary membrane.
We saw in the last chapter that in the large arteries blood may be treated as a homogeneous fluid and its particulate structure ignored. Furthermore, fluid inertia is a dominant feature of the flow in the larger vessels since the Reynolds numbers are large. The fluid mechanical reasons for treating the circulation in two separate parts, with a division at vessels of 100μm diameter, were also given in that chapter. In the microcirculation, which comprises the smallest arteries and veins and the capillaries, conditions are very different from those in large arteries and it is appropriate to consider the flow properties within them separately.
First, it is no longer possible to think of the blood as a homogeneous fluid; it is essential to treat it as a suspension of red cells and other formed elements in plasma. As will be seen later in the chapter, this comes about because even the largest vessels of the microcirculation are only approximately 15 red cells in diameter. Second, in all vessels, viscous rather than inertial effects dominate and the Reynolds numbers are very low; typical Reynolds numbers in 100μm arteries are about 0.5 and in a 10μm capillary they fall to less than 0.005 (see Table I).
In larger arteries, the Womersley parameter α (p. 60) is always considerably greater than unity. In the microcirculation, however, α is very small; in the dog (assuming a heart rate of 2Hz) it is approximately 0.08 in 100μm vessels and falls to approximately 0.005 in capillaries. This means that everywhere in these small vessels the flow is in phase with the local pressure gradient and conditions are quasi-steady.
It soon becomes clear to any student of physiology that there are many systems of units and forms of terminology. For example, respiratory physiologists measure pressures in centimetres of water and cardiovascular physiologists use millimetres of mercury. As the study of any single branch of physiology becomes increasingly sophisticated, more and more use is made of other disciplines in science. As a result, the range of units has increased to such an extent that conversion between systems takes time and can easily cause confusion and mistakes.
We see also frequent misuse of terminology which can only confuse; for example, the partial pressure of oxygen in blood is often referred to as the ‘oxygen tension’, when in reality tension means a tensile force and is hardly the appropriate word to use.
In order to combat a situation which is deteriorating, considerable effort is being made to reorganize and unify the systems of nomenclature and units as employed in physiology. For any agreed procedure to be of value, it must be self-consistent and widely applicable. Therefore, it has to be based upon a proper understanding of mathematical principles and the laws of physics.
The system of units which has been adopted throughout the world and is now in use in most branches of science is known as the Système International or SI (see p. 28).
The science of mechanics comprises the study of motion (or equilibrium) and the forces which cause it. The blood moves in the blood vessels, driven by the pumping action of the heart; the vessel walls, being elastic, also move; the blood and the walls exert forces on each other, which influence their respective motions. Thus, in order to study the mechanics of the circulation, we must first understand the basic principles of the mechanics of fluids (e.g. blood), and of elastic solids (e.g. vessel walls), and the nature of the forces exerted between two moving substances (e.g. blood and vessel walls) in contact.
As well as studying the relatively large-scale behaviour of blood and vessel walls as a whole, we can apply the laws of mechanics to motions right down to the molecular level. Thus, ‘mechanics’ is taken here to include all factors affecting the transport of material, including both diffusion and bulk motion.
The study of mechanics began in the time of the ancient Greeks, with the formulation of ‘laws’ governing the motion of isolated solid bodies. The Greeks believed that, for a body to be in motion, a force of some sort had to be acting upon it all the time; the physical nature of this force, exerted for example on an arrow in flight, was mysterious. The need for such a force was related to one of the paradoxes of the Greek philosopher Zeno: that the arrow occupies a given position during one instant, yet is simultaneously moving to occupy a different position at a subsequent instant.
We saw in Chapter 1 how real materials, in particular fluids, can be regarded as continuous if the distances over which their gross properties (like density) change is much larger than the molecular spacing. They can then be split up into small elements, to each of which the laws of particle mechanics can be applied. We have also set down those laws. Before applying them, however, we must know what forces act on such an element. As with the body sliding along the table (Fig. 2.7), the forces experienced by a representative fluid element are of two kinds: long-range and short-range.
The forces which act at long range, the body forces, are experienced by all fluid elements; the two most common examples are gravitational and electromagnetic in origin. The electromagnetic force on an element depends on quantities like its electrical charge, but the gravitational force, i.e. the weight of the element, depends only on its mass; this is the only example of body force to be considered from now on. If a fluid element P which occupies the point x at a certain time t has volume V and if the fluid in the neighbourhood of x at that time has density ρ, then the gravitational force on the element is ρVg.
Short-range forces are exerted on the element P by those other elements with which it is in contact, and by no other. They consist of all the intermolecular forces exerted by molecules just outside the surface of P on the molecules just inside.
When I arrived at the Physiological Flow Studies Unit, Imperial College, in 1971, the writing of The Mechanics of the Circulation was already underway. The book had been commissioned by Oxford University Press to be delivered in 1972 and the Tuesday afternoon book meeting was a regular event. From the outset, the purpose of the book was seen as presenting cardiovascular mechanics in a rigorous but accessible way. It was not meant to be a textbook, but an introduction to the subject that would be useful to a wide range of readers from medical students to experts in either mechanics or cardiovascular physiology.
The Mechanics of the Circulation was finally published in 1978 and it was obvious that the authors had succeeded in their purpose. It was a truly interdisciplinary book, its authors having trained in medicine, mathematics and engineering, but there was a continuity of style and content that remains unusual in multidisciplinary, multi-author books. Individual authors wrote the first drafts of the different sections of the book closest to their expertise, but they all had an equal say in the final product which, as evidenced by the time it took to write the book and the heat that was generated in those weekly meetings, was no easy task. The book had an enormous impact on the emerging field of cardiovascular mechanics and, by extension, on the development of the discipline of bioengineering as an essentially multidisciplinary field of study. It was reprinted and published as a paperback.
The book had an enormous impact on the emerging field of cardiovascular mechanics and, by extension, on the development of the discipline of bioengineering as an essentially multidisciplinary field of study. It was reprinted and published as a paperback.
Continuing demand for this book confirms that it remains relevant over 30 years after its first publication. The fundamental explanations are largely unchanged, but in the new introduction to this second edition the authors are on hand to guide the reader through major advances of the last three decades. With an emphasis on physical explanation rather than equations, Part I clearly presents the background mechanics. The second part applies mechanical reasoning to the component parts of the circulation: blood, the heart, the systemic arteries, microcirculation, veins and the pulmonary circulation. Each section demonstrates how an understanding of basic mechanics enhances our understanding of the function of the circulation as a whole. This classic book is of value to students, researchers and practitioners in bioengineering, physiology and human and veterinary medicine, particularly those working in the cardiovascular field, and to engineers and physical scientists with multidisciplinary interests.
The mammalian heart consists of two pumps, connected to each other in series, so that the output from each is eventually applied as the input to the other. Since they are developed, embryologically, by differentiation of a single structure, it is not surprising that the pumps are intimately connected anatomically, and that they share a number of features. These include a single excitation mechanism, so that they act almost synchronously; a unique type of muscle, cardiac muscle, which has an anatomical structure similar to skeletal muscle, but some important functional differences; and a similar arrangement of chambers and one-way valves. Not surprisingly, the assumption has often been made that the function of the two pumps will also be similar. Thus it has become common practice to examine the properties of one pump, usually the left, and to assume that the results apply to the other also. This may often be unjustified, particularly in studies of cardiac mechanics, with the result that our knowledge of the mechanics of the right heart and the pulmonary circulation remains very incomplete. It must also be remembered that the scope for experiments on the human heart is very limited, and we must rely heavily on experimental information from animal studies. Thus the descriptions which follow apply primarily to the dog heart.
Many factors which affect the performance of the heart are not our concern in this chapter, among the most important being the wide range of reflexes which act on the heart. For example, nerve endings in the aortic wall and carotid sinus are sensitive to stretch, and thus to changes in arterial pressure.
In the Preface to the first edition, we commented on the benefits and drawbacks of interdisciplinary research; the contributions of specialists to advance our understanding and the difficulty for the non-specialist in understanding these advances. We were thinking particularly about the mechanics of the circulation and the contributions that had been made by engineers, physicists and mathematicians working in collaboration with physiologists and medical doctors. Our goal in writing the book was to alleviate the problem of understanding these advances by providing an introductory text on the mechanics of the circulation that was accessible to physiologists and medical practitioners.
The three decades since the book was published have seen an explosive growth in research on the cardiovascular system. In 1978, bioengineering did not exist as a separate academic discipline and the field of cardiovascular mechanics was relatively small, although it had a long and distinguished history extending over more than three centuries. Today, bioengineering is widely recognized as an academic discipline and interdisciplinary research is generally accepted as essential to progress.
Our understanding of the circulation is immeasurably greater today than it was in 1978, but many problems remain unsolved and cardiovascular disease is still the largest single cause of death world-wide. Again, however, these advances have brought increased difficulty in understanding. We believe that the need for an introductory text on the mechanics of the circulation that is accessible to the non-specialist is even greater now than it was when the book was first published.