Chapter 1

Anatomy and physiology of the respiratory system

This chapter is not intended to provide a comprehensive description of the anatomy and physiology of the respiratory system; rather it is intended to provide a level of understanding that is required to underpin the remainder of this book. Readers wishing to gain a deeper insight into this interesting area are referred to the work of Davies & Moores (2010) and Lumb (2010).

THORACIC STRUCTURE AND FUNCTION

Introduction

This section will describe the principal structures whose physiology will be explored in subsequent sections of this, and other, chapters. It is not intended to provide a detailed description of thoracic structure and function; rather it is intended to provide a working knowledge to facilitate understanding of the applied aspects of this book.

The respiratory system is illustrated in Figure 1.1 and is made up of all the structures that guide air into the lungs (nose, mouth, and airways), plus the lungs themselves and the structures that surround the lungs (thoracic cavity, including the rib cage). The right lung comprises three lobes, whilst the left has two, which allows space for the heart to lie between the left lobes, sloping toward the left. The weight of both adult lungs is between 0.7 and 1.0 kg (1.5 and 2.2 pounds) when weighed at autopsy; however, in life they probably weigh twice this amount because the blood vessels within the lungs (pulmonary circulation) will be filled with about 0.9 litres of blood (weighing about 0.95 kg [2.1 pounds]). In other words, the adult human has about 2 kg (4.4 pounds) of lung tissue hanging inside the rib cage.

Figure 1.1 Schematic diagram of the respiratory system. See text for details. (With permission from Thibodeau GA, Patton KT, 1996. Anatomy and physiology, 3rd edn. Mosby, St Louis.)

The airways

The airways branch a total of 23 times, creating a tree-like structure that ends in the alveoli, where the exchange of oxygen (O₂) and carbon dioxide (CO₂) takes place (Fig. 1.2). The branches follow an irregular, dichotomous pattern in which each airway gives rise to two ‘daughter’ airways. The structure is irregular because the daughter branches may not be of equal size. The number of airways (N) in each generation (Z) is given by the equation N = Z².

Figure 1.2 Diagram illustrating the branching structure of the lung airways. (With permission from Davies A, Moores C, 2010. The respiratory system. Churchill Livingstone, London, p. 15, Fig. 2.4.)

Air enters via the nose and mouth; then it travels into the pharynx, through the glottis and down the trachea. Next, the air travels into the right and left bronchi, and then through the branching structure of the remaining airways to the alveoli. The alveoli are collections of air sacs, similar to a bunch of grapes, which are surrounded by a dense network of capillaries (think of a bunch of grapes inside a net shopping bag; Fig. 1.1). The regions of the lung without alveoli (including the airways) are known as the conducting zone (branches 1–16), whilst the regions with alveoli are known as the respiratory zone (17–23), i.e., the zone where oxygen and carbon dioxide are exchanged (Fig. 1.2). From branch 17 onwards (respiratory bronchioles), the airways begin to display alveolar buds in their walls, and by branch 20 onwards virtually the entire airway is made up of alveoli (alveolar ducts). An important feature of the conducting airways is that the larger airways, such as the trachea, are reinforced with cartilage rings that help prevent collapse, whereas the walls of smaller airways contain no supporting skeleton. The small airways possess rings of smooth muscle that, when contracted, narrow the airways (bronchoconstriction). From branch 3 onwards, the airways are surrounded by lung parenchyma, and the elastic forces that operate to recoil the lung parenchyma help to tug the airways open during exhalation (airway tethering), with their radial traction (see section ‘Mechanics of breathing: Airway resistance’).

The alveoli

The branching structure of the lungs is an impressive work of evolution that has resulted in adult human lungs having a combined surface area of about 60 m² (646 square feet), which is about the same as a singles badminton court and about 40 times the area of the skin (see Fig. 1.23). Why the need for such a huge area? Like so much of evolution, the respiratory system is a slave to the laws of physics. As will be described in detail in the next section, the exchange of oxygen (O₂) and carbon dioxide (CO₂) between the 300 million alveoli and the capillaries surrounding them occurs via passive diffusion. For this process to keep pace with the metabolic needs of the average person, especially during exercise, a vast surface area (number of alveoli and capillaries) is required for diffusion.

Figure 1.3 Drawing taken from an electron micrograph section of an alveolus showing the alveolar–capillary membrane. RBC = red blood cell. (With permission from Davies A, Moores C, 2010. The respiratory system. Churchill Livingstone, London, p.18, Fig. 2.9.)

However, this vast lung surface area would be of little use without the unique and intimate interrelationship that exists between the alveoli and their capillary network. Figure 1.3 illustrates the key feature of this structure, i.e., the minimal distance separating the alveolar air from the capillary blood. Note that on one side of the capillary the alveolar and capillary cells fuse to form a very thin septum, whilst on the opposite side of the capillary the septum is thicker, providing stability and resisting collapse.

The epithelial junctions are sufficiently leaky to allow the passage of water and solutes between the plasma and interstitial fluid, but not larger molecules, whose osmotic potential would cause oedema. These leaks also facilitate the movement of macrophages into the alveolus, where they scavenge foreign bodies (both organic and inorganic). Lining the alveoli and conducting airways is a fluid layer containing surfactant; the importance of this layer for diffusion and normal lung mechanics is explained in subsequent sections. Suffice to say, at this point, dissolving in this layer is one of the sequential steps that O₂ and CO₂ must pass through on their journey.

Respiratory pump muscles

The respiratory pump muscles are a complex arrangement that form a semi-rigid bellows around the lungs. Essentially, all muscles that attach to the rib cage have the potential to generate a breathing action, but the principal muscles are shown in Figure 1.4. Muscles that expand the thoracic cavity are inspiratory muscles and induce inhalation, whereas those that compress the thoracic cavity are expiratory and induce exhalation. These muscles possess exactly the same basic structure as all other skeletal muscles, and they work in concert to expand or compress the thoracic cavity. The structure of the rib cage is described in the section ‘Gross structure of the respiratory system’ (below).

Figure 1.4 The respiratory pump muscles.

Inspiratory muscles

The principal muscle of inspiration is the diaphragm, a domed sheet of muscle that separates the thoracic and abdominal cavities. The diaphragm attaches to the lower ribs, as well as to the lumbar vertebrae. When the diaphragm contracts, the dome flattens, moving downward into the abdominal cavity like a piston (think of a syringe barrel). This movement increases the volume of the thoracic cavity, creating a negative pressure that is proportional to the extent of its movement, and thus, to the force of contraction. Diaphragm contraction also induces the lower ribs to move upward and forward, which also increases thoracic volume. The ribs move outward because the central tendon of the diaphragm (at the crown of the dome) pushes down onto the liver and stomach, which act as a fulcrum. This has the effect of raising the edges of the diaphragm, which are connected to the rib margins, forcing them upward and outward. When the diaphragm moves downward into the abdominal compartment, it also raises intra-abdominal pressure and assists the abdominal muscles in stabilizing the spine. Contraction of the diaphragm is controlled by a single nerve, the phrenic nerve, which originates from the 3rd to the 5th cervical vertebrae.

The muscles of the rib cage are known as the intercostal muscles because they are located in the space between adjacent ribs. Each space contains a layer of inspiratory and a layer of expiratory muscle fibres. The inspiratory intercostal muscles form the outer layer, and they slope downward and forward; contraction causes the ribs to move upward and outward, similar to the raising of a bucket handle. Contraction of these muscles also serves to stabilize the rib cage, making it more rigid, as well as bringing about flexing movements. The stiffening of the rib cage enables it to oppose the tendency to collapse slightly under the influence of the negative pressure generated by the movement of the diaphragm. Without this action, the rib cage would distort, and the action of the diaphragm would be less mechanically efficient, thus wasting energy. Intercostal muscle contraction also brings about stiffening of the rib cage during lifting, pushing and pulling movements, which makes the intercostal muscles important contributors to these actions. The nerves that control intercostal muscle contraction have their origin in the thoracic vertebrae (1st to 11th).

There are also muscles in the neck region with an inspiratory action. The scalene and sternocleidomastoid (sternomastoid) muscles are attached to the top of the sternum, upper two ribs and clavicle at one end; at the other end they are attached to the cervical vertebrae and mastoid process. When these muscles contract they lift the top of the chest, but the scalene muscles are also involved in flexion of the neck. The nerves that control these muscles have their origin in the cervical vertebrae.

Expiratory muscles

The principal muscles of expiration are those that form the muscular corset of the abdominal wall. The most well known and visible of these is the rectus abdominis; the other three muscles are less visible, but arguably more functionally important: the transversus abdominis and the internal and external oblique muscles. When these muscles contract, they pull the lower rib margins downwards and compress the abdominal compartment, raising its internal pressure. The pressure increase tends to push the diaphragm upwards into the thoracic cavity, inducing an increase in pressure and expiration. However, these muscles come into play as respiratory muscles only during exercise or forced-breathing manoeuvres; resting exhalation is a passive process brought about by the recoil of the lungs and rib cage at the end of inspiration (due to stored elastic energy).

The four abdominal muscles involved in breathing also have important functions as postural muscles: in rotating and flexing the trunk, and when coughing, speaking (or singing) and playing wind instruments. The compression and stiffening of the abdominal wall generated by contraction of the abdominal muscles also optimize the position of the diaphragm at the onset of inspiration. This also enhances spinal stability and postural control.

The rib cage also contains muscles with an expiratory action. These are the internal intercostal muscles, which slope backward; contraction causes the ribs to move downward and inward, similar to the lowering of a bucket handle. Both internal and external intercostal muscles are also involved in flexing and rotating of the trunk.

Other respiratory muscles

Theoretically, any of the muscles that attach to the rib cage have the potential to function as respiratory muscles. However, they do so only under extreme conditions such as after spinal injury, or during severe respiratory distress.

Functional properties of respiratory pump muscles

The functional properties of any given muscle are determined by the type of muscle fibres it contains. Human muscles have three main types of fibres, and most muscles contain a mixture of these, in differing proportions. The relative proportions of these three fibre types determine the properties of each muscle:

• Type I: Slow contracting and relatively weak, but very resistant to fatigue

• Type IIA: Moderately fast and strongly contracting, with high resistance to fatigue

• Type IIX (also known as type IIB): Fast and very strong, but with only moderate resistance to fatigue.

Type I and IIA fibres have a high oxidative capacity (ability to use oxygen to liberate energy) and a high to moderate density of blood capillaries (delivering oxygen). These fibres are also known as oxidative fibres, and they are capable of sustaining activity for prolonged periods without becoming fatigued.

It comes as no surprise to learn that the proportion of oxidative fibres (type I and type IIA) within the diaphragm and inspiratory intercostals is approximately 80% (Gollnick et al, 1972), whilst that of the expiratory intercostals is almost 100%. This compares with around 35–45% for limb muscles (Gollnick et al, 1972). The fibres of the abdominal muscles tend to be much more variable in their composition, reflecting the multiplicity of their roles. Another important factor determining muscle fatigue is its blood supply. Inadequate blood flow (ischaemia) not only limits oxygen delivery, it also limits the delivery of substrates and the removal of metabolic by-products, all of which can hasten fatigue. The diaphragm and rib cage muscles are supplied by numerous arteries. The diaphragm, for example, is perfused by three arteries, as well as benefiting from anastamoses that provide collateral sources of blood flow between arteries. The diaphragm also has an extremely dense capillary network and a capacity to increase its blood flow that exceeds that of limb muscles (Polla et al, 2004). The diaphragm maintains perfusion at contraction forces that occlude blood flow in limb muscles. This advantage derives from the fact that it is a thin sheet of muscle that produces a negative intrathoracic pressure during contraction; this pressure gradient maintains blood flow (Buchler et al, 1985). It has been suggested that this abundant and persistent arterial supply protects the diaphragm fibres from ischaemia (Hussain, 1996), providing resistance to fatigue.

In the past, the highly fatigue-resistant characteristics of the respiratory pump muscles contributed to a key assumption regarding the likelihood that the respiratory muscles contributed to exercise limitation. Physiologists assumed that the respiratory pump muscles, especially the diaphragm, were so well evolved from their continuous work that they were immune to fatigue. It wasn’t until the 1990s that this myth was finally shattered, when exercise-induced diaphragm fatigue was measured in healthy young athletes (see Ch. 3, section ‘Respiratory muscle involvement in exercise limitation, Healthy people’).

Upper airway muscles

The first question to address is why upper airway muscles are relevant to breathing. The simple answer is that, without them, upper airway resistance would be intolerable. During normal resting breathing, the vocal folds abduct during inhalation in order to widen the laryngeal glottic opening, permitting unobstructed air flow through the larynx (Brancatisano et al, 1984). This occurs via reflex activation of the posterior cricoarytenoid (PCA) muscle. Without this activity, the vocal folds would collapse across that laryngeal opening, causing an increase in resistance to upper airway flow and leading to increased breathing effort and dyspnoea. The strength of contraction of the PCA muscles has been shown to be proportional to factors that are associated with increased levels of respiratory drive, as well as the negativity of intrathoracic pressure (Suzuki & Kirchner, 1969). During vigorous breathing the action of the PCA is supplemented by contraction of the cricothyroid (CT), which acts to tension the vocal folds, increasing the anteroposterior dimension of the larynx (Hoh, 2005). Active closure of the vocal folds (adduction) is performed by the lateral cricoarytenoid muscle (LCA), thyroarytenoid (TA) and interarytenoid (IA), but only the PCA is involved in resting breathing. However, during tidal breathing most of the closure is brought about by relaxation of the PCA rather than by activation of the adductor muscles (Murakami & Kirchner, 1972). Transient, reflex modulation of the area of the laryngeal portion of the airway plays an important role in controlling breathing frequency, duty cycle and end-expiratory lung volume, as narrowing of the airway provides an important braking effect during expiration. Active adduction is associated with activities such as vocalization, coughing and straining.

The fibre type of human laryngeal muscles has not been studied nearly so extensively as limb muscles, but a number of key observations have been made with respect to the vocal fold abductors (PCA and CT). The PCA and CT contain around 66% and 45% type I fibres, respectively. The type II fibres of these muscles are limited to IIA and IIX, but the latter are very few in number. In common with limb muscles, PCA and CT appear to contain no IIB fibres (Hoh, 2005). The proportion of fast IIX fibres appears to be larger in the adductor muscles (TA and LCA), which probably imparts a higher velocity of shortening. This may be functionally important in their role as protectors of the airway (Li et al, 2004).

Because of its role in vocalization, the LCA has been studied in relation to its fatigability. Intramuscular EMG (electromyography) suggests that prolonged, loud vocalization exercises result in changes within the EMG that are consistent with the development of muscle fatigue (Boucher et al, 2006). Thus, it is reasonable to suggest that under similarly challenging conditions for abduction (e.g., vigorous breathing) PCA and CT might be similarly susceptible to fatigue. This is discussed in relation to exercise intolerance in Chapter 3 (section ‘Respiratory muscle involvement in exercise limitation’).

Gross structure of the respiratory system

The respiratory system is housed within the thoracic cavity, which is formed by the rib cage, vertebrae, sternum and diaphragm. Within the thorax there are three further cavities: the left and right pleural cavities and the mediastinum (Fig. 1.5).

Figure 1.5 Gross anatomy of the lungs. (With permission from Davies A, Moores C, 2010. The respiratory system. Churchill Livingstone, London, p. 21, Fig. 2.12.)

The arrangement and movements generated by the respiratory muscles are described above (in ‘The muscles’). The skeletal structures that translate the muscle actions into movements are complex. The rib cage structure is such that the vertebral articulation of the ribs is higher than the sternal attachments; consequently, the ribs slope downwards anteriorly (Fig. 1.6).

Figure 1.6 The rib cage.

All 12 ribs articulate with the vertebrae, but only the first six connect individually to the sternum. Ribs 7–10 articulate with the lower sternum via a common cartilage, whilst ribs 11 and 12 have no anterior connections (‘floating ribs’). The head of most ribs articulates with the bodies of two adjacent vertebrae, whilst their tubercles articulate with the transverse process of one of these vertebrae. Nerves and blood vessels run in a channel on the underside of the ribs called the costal groove (Fig. 1.7).

Figure 1.7 The ribs and their articulations.

The sternum has three parts: the manubrium, body and xiphoid process (xiphisternum). The junction between the manubrium and body of the sternum (sternal angle) is a useful anatomical landmark as it marks the level of the bifurcation of the bronchi (carina) and the second rib.

The process by which breathing is brought about is described in the sections ‘The muscles’ and ‘Mechanics of breathing’.

GAS EXCHANGE

Diffusion

Gas exchange is the process of transferring gases across the alveolar and capillary membranes and it requires both diffusion of gas and perfusion of blood. Diffusion is a passive process, and it is for this reason that the lungs have evolved the structure that we see in terrestrial mammals. The key features of the lungs’ passive diffusion system are:

• An adequate diffusion gradient

• A large surface area for contact between air and blood

• A short diffusion distance between air and blood.

It is easy to see how disease can affect all three of these factors, sometimes simultaneously, leading to a reduction in diffusing capacity.

The diffusion gradient is provided by the difference in partial pressure of the gases (P). The partial pressure of a gas is the proportion of the total barometric pressure that the gas contributes. For example, oxygen (O₂) makes up 21% of the atmosphere; if barometric pressure is 760 mmHg (‘standard’ atmospheric pressure), the partial pressure of oxygen (PO₂) is 20.93% of 760 mmHg, i.e., 159 mmHg. As air enters the alveolus, it is warmed and humidified, and water vapour contributes 47 mmHg pressure. Since total barometric pressure cannot change, the partial pressure of all of the other gases is reduced in proportion to the amount of water added. In the case of PO₂ it is reduced to 149 mmHg:

However, the partial pressure of oxygen within the alveoli (P_AO₂) is not 149 mmHg because the inhaled breath is diluted by the air that remained in the lungs at the end of the previous breath (end-expiratory lung volume, EELV). The extent of the dilution depends upon a number of factors, including the EELV and the tidal volume (V_T); typically P_AO₂ will be around 104 mmHg, giving a diffusion gradient of around 65 mmHg. Thus, V_T affects both the flow of gas delivered to the alveoli (via the dead space to V_T ratio; see ‘Lung volumes and capacities’, below), and the extent to which inspired PO₂ (P_IO₂) is diluted by the EELV (inspired to alveolar gradient). This mixing of old and new gas also affects the diffusion gradient and exchange of CO₂ because it has the effect of raising the partial pressure of CO₂ (PCO₂) in the alveoli (P_ACO₂). Thus, it is easy to see how changes in breathing pattern can influence the driving pressure for gas exchange, leading to hypoxaemia and hypercapnia.

Under normal conditions, the movement of oxygen across the alveolar and capillary membranes is so efficient that the PO₂ of the arterial blood leaving the lungs (P_aO₂) is very close to the P_AO₂. This is known as the a–A gradient, and an increase in this gradient is a sign that all is not well with the process of diffusion. Both the diffusion surface area and the diffusion distance can influence the a–A gradient, as well as how quickly the blood traverses the alveolar capillaries. Despite the diffusion gradient for CO₂ being much smaller than that for O₂ (around 5 mmHg compared with 65 mmHg, respectively), equilibration of pulmonary arterial and alveolar PCO₂ is normally achieved. This is made possible by the fact that the solubility coefficient of CO₂ is 23 times that of O₂.

The reason that solubility affects diffusion efficiency is explained by Fick’s law, which describes the rate of movement of gases across a membrane:

where A is the diffusion area, S is the solubility coefficient of the gas, ΔC is concentration gradient for the gas (alveolar to pulmonary arterial), t is the membrane thickness (alveolar plus capillary), and MW is the molecular weight of the gas molecule (its physical size). Although CO₂ is 23 times more soluble than O₂, it has a larger MW making the actual diffusion rate 20 times greater. However, equilibrium between the alveolus and venous blood occurs at around the same time for both CO₂ and O₂ because of the lower ΔC and slower release of CO₂ from the blood compared with that of O₂. Importantly, the A in the Fick equation is not the lung surface area, but rather the surface area where there is both ventilation and perfusion, i.e., where air and blood meet. As will be explained in later sections, many factors can influence the distribution of both ventilation and perfusion, leading to ventilation / perfusion ( / ) inequality, a reduction in A and an impairment of diffusion.

Clinically, disease can affect the diffusion area, the concentration gradient and the diffusion distance (t). Problems with diffusion manifest first as hypoxaemia, because O₂ can be brought closer to the limits of its diffusional capacity by disease. In contrast, hypercapnia is normally a sign of deficiencies of alveolar ventilation.

There is one final factor that influences the efficiency of gas exchange between alveolus and blood, viz., the characteristics of the blood supply to the alveolus, and in particular the time available for the diffusion and binding / release of O₂ and CO₂. Figure 1.8 is a diagrammatic illustration of the change in pulmonary blood gases as the blood traverses the lungs. Under resting conditions, the blood spends around 0.75 seconds in contact with the alveolar regions of the lung, during which time it will traverse a number of alveoli.

Figure 1.8 Equilibrium time for O₂ and CO₂ as blood traverses the alveolar capillaries under resting conditions. (With permission from Hicks GH, 2000. Cardiopulmonary anatomy and physiology. WB Saunders, Philadelphia, p. 365, Fig. 12-17.)

It is clear from Figure 1.8 that equilibration of both gases occurs early in the journey through the capillary, and that within 0.25 seconds diffusion ceases because there is no longer a gradient and exchange is complete. The only way to increase the exchange of gas is to increase the throughput of blood. In this scenario, gas exchange is perfusion limited. Many people find it hard to understand that, in healthy people at sea level, breathing more during exercise does not improve the amount of oxygen leaving the lungs; this is because it’s already ‘as good as it gets’. However, diffusion limitation can arise in healthy people under very specific conditions including: (1) exposure to high altitude (reducing the diffusion gradient), (2) during maximal exercise, when (a) cardiac output can be so high that blood traverses the lung capillaries before full equilibration can take place, (b) cardiac output can be so high that it outstrips the ability of the respiratory pump to deliver adequate alveolar ventilation (V_A), (c) / inequality develops due to the mechanical effects of acute pulmonary oedema compressing alveoli and capillaries, and (d) the diffusion distance is increased by acute pulmonary oedema. Exercise-induced arterial hypoxaemia in healthy well-trained individuals at sea level is relatively rare and the specific contributions of the putative contributor remains incompletely understood (Guenette & Sheel, 2007).

In contrast to the rarity of diffusion limitation in healthy people, disease can inflict structural damage and functional changes that render affected individuals diffusion limited. For example:

• Loss of diffusion area due to destruction of lung tissue, and / or lung volume loss

• Alveolar hypoventilation due to mechanical constraints and breathing pattern abnormalities

• / inequality due to disturbed lung mechanics and breathing pattern abnormalities

• Increased diffusion distance due to fibrosis and oedema.

Perfusion

In the previous section, we touched upon some perfusion-related factors that affected diffusion, e.g., diffusion area. Perfusion is such an important part of the gas exchange process that it merits specific consideration in relation to gas exchange; after all, under normal conditions, gas exchange is perfusion limited.

The pulmonary vasculature is supplied via a separate, low-pressure branch of the cardiovascular system. Deoxygenated blood is returned to the lungs via the right side of the heart and the pulmonary artery. The latter is the only artery in the body to carry deoxygenated blood, which is distributed to a huge capillary network within the lungs (Fig. 1.9).

Figure 1.9 Schematic depicting pulmonary and systemic circulations and pressures. (With permission from Thibodeau GA, Patton KT, 1995. Anatomy and physiology, 3rd edn, Mosby, St Louis.)

As well as illustrating the flow of blood through both branches of the circulation, the diagram in Figure 1.9 also illustrates the pressures present within each part. Systolic / diastolic pressure in the pulmonary artery is around only 24 / 9 mmHg, compared with 120 / 80 mmHg in the aorta. The pulmonary circuit is at low pressure because of the thin, delicate walls of the capillary network, which minimizes the diffusion distance. Even small increases in pulmonary arterial pressure lead to fluid leakage and pulmonary oedema. Since the pulmonary circulation receives virtually the entire cardiac output, the fact that the pressures within it are low indicates that it has a low resistance. The reason for this low resistance is the extensiveness of its capillary network; as was described above, the capillary network can be thought of as a sheet of blood enveloping the alveoli.

Once gas exchange has taken place, the blood is returned to the left side of the heart to be distributed via the systemic circulation. In this way, the two parts of the circulation function in series, driven by a single pump. The difference in the pressures within the two sides of the circulation has a dramatic influence on the structure of the two sides of the heart: the muscular wall of the right ventricle is much thinner than that of the left, reflecting the lower resistance of the pulmonary circulation.

During exercise, cardiac output may increase from ~ 5 l·min⁻¹ to ~ 25 l·min⁻¹. This is accompanied by a small increase in systemic arterial blood pressure, and blood flow increases to exercising muscles because of vasodilatation in their vascular beds. In contrast, the pressure within the pulmonary circulation (receiving the same cardiac output) remains virtually unchanged during exercise. This is because the thin-walled pulmonary blood vessels distend, reducing pulmonary vascular resistance (PVR). In addition, there is recruitment of blood vessels in the pulmonary circulation; under resting conditions, not all blood vessels in the lungs are open fully (patent), but during exercise these vessels are recruited, and distended, stabilizing PVR.

One factor that has a strong influence upon the patency of pulmonary capillaries is alveolar pressure, which can compress the vessels. This increases their resistance, leading to redistribution of blood and heterogeneity of blood flow within the lungs. In addition, gravity, which also influences alveolar pressure (see ‘Pressures within the thorax’, below), has a potent influence upon blood flow distribution within the lungs. The effect is due to the hydrostatic pressure gradient that exists from the apex to the base of the lungs. It is very potent because pulmonary arterial pressure is so low that it is only just sufficient to pump blood to the lung apices. Perfusion pressure at the base of the lungs is equivalent to pulmonary arterial pressure, plus the hydrostatic pressure difference between the heart and base of the lungs. At the apex, perfusion pressure is equivalent to pulmonary arterial pressure, minus the hydrostatic pressure difference between the heart and apex of the lungs. This means that blood flow is distributed preferentially to the base of the lungs. As will be described in a later section (‘Pressures within the thorax’), ventilation is also distributed preferentially to the base of the lungs. However, the relative distribution of ventilation and perfusion is imperfect; there is around a three- to four-fold difference in ventilation from apex to base, compared with only a 16-fold difference in perfusion. Accordingly, there is a gradient of ventilation perfusion ratios ( / ), and gas exchange, throughout the lungs. These variations in gas exchange also lead to local variations in the alveolar gas partial pressures. These phenomena are summarized in Figure 1.10.