In Figure 2.1 the subject is breathing through his nose because the lips are closed and the tongue lies against the palate. When you breathe through the mouth – for example when you blow out a candle or suck through a straw – the soft palate is arched upward to form a seal against Passavant’s ridge at the top of the pharynx. This form of airways obstruction is a normal function. Similarly, under normal circumstances, the genioglossus muscle of the tongue has a high resting tone in conscious subjects, and this holds the tongue forward, preventing it from obstructing the airway. During sleep, and particularly in those suffering from the dangerous condition of obstructive sleep apnoea, the tongue falls against the back wall of the pharynx and obstructs breathing. The muscle tone of the pharynx itself becomes reduced, particularly during REM (rapid eye movement) sleep and in OSA the pharynx collapses under the negative pressure of inspiration. Blocking of the airways by the tongue also and almost inevitably occurs during general anaesthesia and requires immediate attention from the anaesthetist.

Most, but not all, healthy persons breathe through the nose unless exercising. The resistance to breathing of the nose is about twice that of the mouth and nearly half the total resistance of the airways. The disadvantage of this is offset by the advantage obtained by the air-conditioning and filtering activities of the nose, which warm, moisten and filter the air before it comes in contact with the delicate respiratory regions of the lungs. Newborn babies have great difficulty breathing through their mouths: they are almost obligate nose breathers and become very distressed when their nose is blocked. Their predominantly nose breathing may be associated with their ability to suckle and breathe at the same time. On the other hand, many animal species, such as rabbits, manage to eat and breathe at the same time by having lateral food channels on either side of the larynx (see below) that bypass the airway. Marine mammals such as whales have completely separate air and food channels, with the airway ending at the back of the head.

In humans the nose extends from the nostrils (external nares) to the choanae (internal nares), which empty into the nasal part of the pharynx. Each nostril narrows to form its nasal valve, and at this level the total cross-sectional area of the airways is narrower (3 mm²) than anywhere else in the system. This narrowing imposes the majority of the high resistance to airflow found in the nose (see Chapter 5) and, combined with the sharp turn the inspiratory air must make as it enters the wide (140 mm²) lumen of the cavum of the nose, causes turbulence. The walls of the nasal cavum are rigid bone projecting out into the airway from the lateral walls as the turbinates. These have a large surface area (150 cm²) covered by vascular mucosal erectile tissue important in the ‘air-conditioning’ activities of the nose. This mucosal tissue can swell considerably in conditions such as rhinitis (described above), and it is here that nasal decongestants such as oxymetazoline, an agonist of α adrenergic receptors on vascular smooth muscle, act to clear a blocked nose by causing the vascular smooth muscle to contract.

Case 2.1 Structure of the respiratory system: 1

Obstructive sleep apnoea

Mr Sinclair is 50 years old. He is rather overweight for his height: he is 168 cm tall but weighs 102 kg. He also drinks rather heavily and is a smoker.

For the past 2 years, Mrs Sinclair has slept in a different room from Mr Sinclair because of his very loud snoring and restlessness at night. Recently, Mr Sinclair has been feeling more and more tired during the day. For some time, he has been regularly falling asleep when he arrives home from work. Over the past month or so, he has found it increasingly difficult to concentrate at work and on one occasion recently, he was caught sleeping at his desk by his manager and he is facing disciplinary action. Mrs Sinclair eventually persuaded her husband to visit his doctor.

Mr Sinclair’s doctor referred him to a specialist in sleep medicine. The doctor suggested that he may be suffering from obstructive sleep apnoea (OSA). He explained that during periods of deep sleep, Mr Sinclair’s airway was becoming obstructed. During an episode of obstruction, Mr Sinclair’s sleep becomes lighter until the obstruction is overcome. These episodes of obstruction and sleep interruption are responsible for Mr Sinclair’s daytime sleepiness. The doctor went on to suggest that Mr Sinclair might be treated with a nasal continuous positive airway pressure device.

In this section we will consider:

1. What causes obstructive sleep apnoea?

2. What are the signs, symptoms and treatment of obstructive sleep apnoea?

Normal physiological swelling of the mucosa and consequent restriction of airflow takes place asymmetrically over a period of time, so that one nasal passage is more constricted than the other. Thus both nasal passages are not uniformly constricted, with the major constriction, and therefore airflow, alternating between nostrils over a period of hours. This oscillation of airflow may help to sustain the nose in its air-conditioning activities by allowing one channel to rest while the other carries out most of the work.

The major function of the upper airway is to air-condition the inspirate. It is not essential to breathe through the nose to do this, and the mouth will make a fairly good job of warming and humidifying inhaled air before it reaches the larynx. However, the mouth has not evolved for that purpose and the unpleasant consequences of using it are well known to anyone who has had to breathe through their mouth because a cold has obstructed their nasal airways.

The larynx – intubation of the airways

A common cause of accidental airway obstruction is the inhalation of food into the trachea. Normally, to prevent this during swallowing, the larynx, a box-like structure at the upper end of the trachea, is elevated (moved towards the head) by the muscles attached to it and the epiglottis folds backward, forming a very effective seal, like the ‘trapdoor’ over the entrance to the larynx. Because the ‘trapdoor’ can only open outwards, increased pressure in the pharynx makes the seal of the epiglottis on the larynx tighter and it can withstand considerable inward pressures of up to 100 kPa.

If this system of preventing solids entering the airways fails, powerful cough reflexes can be provoked by nerves in the lining of the larynx and trachea.

The larynx (see Fig. 2.1) is in fact a rather complicated box made up of plates of cartilage. It can be closed off by drawing together the two curtains of muscle which make up the vocal folds across the lumen of the larynx. Effective coughs depend on the closure and rapid opening of these ‘curtains’, which under less extreme circumstances are used to produce and modify the sounds that make up speech. The vocal folds can be drawn together so strongly that they are airtight against the greatest efforts to breathe the subject can make. This is clearly a ‘bad thing’ and can occur accidentally when an anaesthetist is trying to get an endotracheal tube into a patient’s trachea. This dangerous closing of the larynx is called laryngospasm. A picture of what an anaesthetist would see when approaching the larynx is shown in Fig. 2.2.

Fig. 2.2 The vocal folds, as might be seen by an anaesthetist about to intubate a patient.

Bronchoscopy

It is frequently useful to inspect the airways below the larynx. First the trachea (part of which is extrathoracic), and then the intrathoracic airways. The instrument used for this is called a bronchoscope and may be of the rigid ‘open tube’ type through which the airways are inspected, or the flexible fibreoptic variety (Fig. 2.3) which, as well as providing a view of the inside of the airways through its fibreoptic system, contains channels through which a variety of sampling and surgical instruments may be passed. Each type of bronchoscope has its advantages, but 95% of bronchoscopic procedures carried out these days are fibreoptic. Biopsy forceps, brushes and needles, balloon catheters and laser fibres can all now be passed through flexible bronchoscopes to carry out procedures after an initial inspection of even very small intrathoracic airways.

Fig. 2.3 Bronchoscopes. Both fibreoptic flexible (A & C) and rigid (B & D) types are shown. The vast majority of investigations these days are carried out with the flexible type. To insert the rigid bronchoscope the patient’s head has to be raised and rotated as shown.

The intrathoracic airways

The trachea is a single tube leading from the extrathoracic environment of the neck, where it is anchored at one end at the larynx, into the intrathoracic environment containing the lungs. It is the first of the conducting airways of the lungs. The conducting airways, as their name implies, conduct air to the respiratory airways, where the exchange of gas that makes up respiration takes place. The structure of these conducting airways differs from that of the respiratory region, mainly in having cartilage and smooth muscle in their relatively thick walls. This cartilage is particularly prominent in the trachea, where it forms horseshoe-shaped incomplete rings, with the two free ends facing backward and closed with a layer of smooth muscle (trachealis) with the oesophagus lying against it.

The airways of the lungs are often referred as the bronchial tree, and casts in which the airways are filled with plastic material and then the tissues dissolved away look like a deciduous tree in winter. The branches of this ‘tree’ can be represented in diagrammatic form as the ‘generations’ of a family tree (Fig. 2.4). In some bronchitic patients secretions sometimes fill small airways, solidify, and are coughed up as small ‘casts’ of part of this ‘tree’.

Fig. 2.4 The naming of airways. There is of course a gradual change in structure from one type of airway to another. One particular type of airway can occur at different distances into the lungs. (After Weibel, 1963)

The trachea is the first and largest of about 23 generations of airways. The airways of each generation arise from the previous one by a system of irregular dichotomous branching airways. Dichotomous because each ‘mother’ airway gives rise to two ‘daughter’ airways, and irregular because the daughters, although smaller than the mother, are not necessarily of equal size. The naming of these generations is illustrated in Figure 2.4, from which it may not be obvious that the number of airways (N) in a generation (Z), (counting the single trachea as generation 0) is:

The effect of dichotomous branching of individual airways on the total cross-sectional area (the sum of the cross-sectional areas of all the airways at that level) is remarkable and is shown in Figure 2.5. Notice that ‘Total cross-sectional area’ is measured on a log scale, and so this value increases much more than it appears to in the figure.

Fig. 2.5 Total cross-sectional area of the human airways. The total cross-sectional area at any level in the bronchial tree is the sum of the cross-sectional areas of all the airways at that level.

The functional consequences of this increase are profound because it causes the velocity of the air to fall rapidly as it moves into the lung. This effect is discussed in more detail in Chapter 5. The dimensions of some of the airways that make up the bronchial tree are given in Table 2.1.

Table 2.1

Dimensions of some of the airways of the human tracheobronchial tree. Note the enormous increase in cross-section and percentage total volume in the last few generations

As you go deeper into the lung the transitional and respiratory generations of the airways bear more and more alveoli until the alveolar sacs are totally made up of them. Alveoli do not look like the bunches of grapes or balloons stylistically represented in many textbooks, but rather pock-marked cavities with holes (pores of Kohn, K in Fig. 2.7C) between many adjacent alveoli and with macrophages wandering over their surface ready to engulf and digest foreign particles (see Figs 2.6, 2.17).

Fig. 2.6 Scanning electron micrograph of an alveolus. A, alveolus; C₁, C₂, C₃, capillaries; E, endothelial cell; P₁, type I pneumocytes; P₂ type II pneumocyte; L, lamellar bodies. From Young and Heath 2000.

It is a testament to the remarkable power of evolution that computer models which can analyse a branching system of tubes tell us that the branching angles and the changes in diameter of the airways of the human lungs are just right to cram the maximum alveolar surface into the minimum volume.

Histological structure of the airways

The microscopic structure of the wall of the airways changes as you go deeper into the lungs. Three ‘snapshots’ of airway wall structure are shown in Figure 2.7 but of course the structure changes gradually from generation to generation.

Fig. 2.7 Airways wall structure. The classification of airways would depend on the characteristics of structure illustrated here. (A) Bronchus; (B) bronchiole; (C) alveolus. RBC, red blood cell; K, pores of Kohn; EP, epithelial nucleus; EN, endothelial nucleus.

The conducting airways consist of three general layers which vary in proportion depending on airway type:

• The inner mucosal surface consists of ciliated epithelium and underlying mucus-secreting goblet cells. The activity of the cilia and the secretions of the globlet cells make up the mucociliary escalator (see Air-conditioning, below), which is important in removing inhaled particles in the lungs.

• Outside the mucosal layer comes a smooth muscle layer in which the fibres are in continuous bundles. This smooth muscle is found in decreasing amounts from the largest airways right down to the entrances to the alveoli.

• The outermost layer is of connective tissue, which in the large bronchi contains supporting cartilage. As the airways penetrate the lung they first lose their cartilage support and smooth muscle occupies a greater percentage of the airway wall. Then the ciliated epithelium becomes the squamous type, finally forming the respiratory region of the lung.

Bronchitis and the Reid Index

The arrangement representing bronchial structure illustrated in Figure 2.7 and described above is modified in chronic bronchitis in a way that provides a histopathological quantitative diagnosis of the disease. The Reid Index provides a measure of proportion of bronchial glands to total wall thickness (Fig. 2.8). In normal lungs mucous glands occupy less than 40% of total wall thickness. In chronic bronchitis this proportion is altered by hyperplasia of the glands. A characteristic of chronic bronchitis is an increase in the products of these glands.

Fig. 2.8 The Reid Index. The percentage of bronchial wall thickness occupied by gland tissue is known as the Reid Index, and is used as a measure of chronic bronchitis.

The respiratory region

The respiratory regions of the lungs show a wonderful degree of adaptation. They carry out the functions of a respiratory surface while withstanding the assaults of a polluted atmosphere and the mechanical trauma of being stretched and then relaxed about 12 times a minute for the whole of your life as a result of the movements of breathing.

One of the characteristics of the respiratory surface of any animal is that it should be thin, offering minimal separation between the outside medium (air or water) and the blood. This is beautifully demonstrated in the lungs, which are the only place in our body where blood capillaries come into direct contact with the outside air, as a result of the fusion of the type I epithelial cells (which make up about 95% of the lining of the respiratory zone; Fig. 2.6) with the pulmonary capillary endothelium. This fusion results in an ultrathin layer ideal for the diffusion of gas but not much good for support. Evolution has resulted in this thinning occurring on only one side of the pulmonary capillaries, whereas the cells on the other side remain separate and more robust, supporting the capillary in its place (Fig. 2.9).

Fig. 2.9 The alveolar–capillary membrane. This diagram of an electron micrograph shows the way the alveolar and capillary cells on one side of the alveolar septum fuse to form an ultrathin layer which offers little barrier to diffusion. The other side of the septum is thicker and provides physical support. RBC, red blood cell.

The junctions between the endothelial cells of the capillaries are ‘leaky’ and allow an easy flux of water and solutes between the plasma and the interstitial space. The junctions between the epithelial cells, however, are sufficiently ‘tight’ to prevent the escape of large molecules such as albumen into the alveoli, which would result in pulmonary oedema. Macrophages can easily push their way through the epithelial junctions to carry out their scavenging activities on the air side of the alveolus.

The rounded type II cells, much less numerous than type I and found at the junctions of alveolar septa, are the stem cells from which type II epithelial cells are formed. They are also important in producing lung surfactant (see Chapter 3).

Blood vessels

The pulmonary circulation only offers one-sixth of the resistance to blood flow that the systemic circulation offers. It is therefore a low-pressure system and this is reflected in the thin walls of its arteries. These arteries follow the airways through the lungs in connective tissue sheaths. The pulmonary arterioles are also very different from systemic arterioles, having very little smooth muscle in their walls. This absence of smooth muscle in the arterioles, and of course the capillaries and venules, persuades many scientists to consider the microcirculation of the lungs as a whole, rather than making a special case of the capillaries, which snake along several alveolar walls, one after the other, before reaching the venules. Venules join to form veins which, unlike the arteries, do not travel with the airways but make their own way along the septa that separate the segments of the lung. The airways and pulmonary blood vessels down as far as the terminal bronchioles receive their nutrition from the bronchial circulation which, as part of the systemic circulation, is distinct from the pulmonary circulation of the lungs. Part of the bronchial circulation returns to the systemic venous system in the normal way, but part drains into the pulmonary veins, ‘contaminating’ their oxygenated blood with deoxygenated blood. This situation constitutes a ‘shunt’ (see Chapter 7, p. 97).

Pulmonary hypertension

Hypertension (high blood pressure) can occur in the pulmonary circulation as well as in the systemic circulation. Pulmonary mean arterial pressure is normally about 15 mm Hg. This means that the limited smooth muscle in the pulmonary system is normally quite adequate to control flow. Pulmonary hypertension can arise for extrapulmonary reasons, such as mitral stenosis or left ventricular failure, both of which prevent the heart pumping away blood returning from the lungs. Congenital defects which allow blood to pass from the left (high-pressure) side of the heart to the pulmonary circulation also produce pulmonary hypertension.

By far the most common causes of pulmonary hypertension are changes in the pulmonary vessels themselves. They may be blocked by emboli, circulating fat, amniotic fluid or cancer cells. They may be obliterated by destruction of the architecture of the capillary beds by emphysema, or the smooth muscle in their walls may be provoked to contract by low oxygen tension, resulting from high altitude or diseases such as bronchitis and emphysema.

The clinical features of pulmonary hypertension are mainly the result of the increased pressure, producing oedema in the lung and imposing a pumping load on the right heart which it has not evolved to cope with. The patient complains of chest pain, dyspnoea and fatigue. Heart sounds are modified and the ECG demonstrates right ventricular hypertrophy.

The lymphatics

The perivascular spaces of the alveolar wall are drained by lymph vessels. The lymph system of the lungs begins as tiny blind-ended vessels just above the alveoli. These join to form lymphatics in close approximation to the blood vessels and airways. They are an important feature in the control of fluid balance in the lung and can contain considerable amounts of lymph, particularly during pulmonary oedema, when they produce the characteristic ‘butterfly shadow’ on the chest X-ray (Fig. 2.10).

Fig. 2.10 X-ray of ‘butterfly shadow’ in pulmonary oedema.

As in other tissue the lymph system plays a key role in immune defence in the lungs. These reactions are more the province of a textbook of immunology, but can be classified in outline as:

• immediate hypersensitivity

• antibody-dependent cytotoxicity

• immune complex reactions

• cell-mediated immune reactions.

Many immune disorders have the characteristics of asthma, whereas those causing interstitial lung disease are characterized by restrictive patterns (see Chapter 4).

The nerves

Innervation of the airways of the lungs is separate from that which brings about breathing (see below) and consists of afferent and efferent parts. The most dramatic efferent (motor) effects produced are on bronchomotor tone. The parasympathetic efferent supply is of most importance in this, and arrives at bronchial smooth muscle via preganglionic fibres which course through the jugular and then the nodose ganglia of the vagus nerves. As this is a parasympathetic outflow the fibres synapse in ganglia on the bronchi before sending short postganglionic fibres to the bronchial smooth muscle where they release acetylcholine to produce bronchoconstriction (Fig. 2.11).

Fig. 2.11 Innervation of the diaphragm, intercostal muscles and lungs. The efferent (motor) systems are shown. The afferent (sensory) system is mainly in the vagus nerves.

The sympathetic nervous system, which is anatomically represented, has yet to be proved to have functional importance. The NANC (non-adrenergic non-cholinergic) system, which runs in the vagus nerve, secretes a variety substances that contract and relax bronchial smooth muscle, depending on circumstances.

Afferent nerves from receptors near the alveoli (J receptors), in the smooth muscle of airways (stretch receptors), and free nerve endings between the epithelial cells of airways (rapidly adapting, irritant, receptors) conduct sensation and sensory reflex information from the lungs to the brain, where it influences patterns of breathing (see Chapter 11) and bronchomotor tone.

The pulmonary circulation is innervated by sympathetic and parasympathetic nerves, but unlike the situation in the airways the sympathetic supply is of greater functional importance than the parasympathetic, and even then it only appears to exert a significant effect under conditions requiring ‘fight or flight’.

The limited importance of all these nervous systems is demonstrated by the success of transplanted lungs which are in fact denervated!

Gross structure of the respiratory system

As with other organs the general name for the functional tissue of the lungs is parenchyma. The vast majority of the volume of what we see as the lungs when the chest is opened is in fact alveolar tissue surrounding air spaces (see Table 2.1). These air spaces make the lungs so insubstantial and light that they are the only organ that floats when placed in water, hence the Middle English name for lungs: lights.

Each lung is anatomically divided into lobes, made up of segments which are subdivided into lobules (Fig. 2.12).

Fig. 2.12 Gross anatomy of the lungs. Each lung is divided into lobes made up of segments subdivided into lobules by fibrous tissue.

The lungs lie on both sides of the mediastinum which contains the trachea, heart, major blood vessels, nerves and oesophagus. The trachea divides into the right and left main bronchi at the carina, which is close to the aortic arch and the division of the pulmonary artery into its left and right branches. The main bronchi, pulmonary arteries and veins penetrate each lung at the hila. The lobes of the lungs are covered, except at their ‘roots’ at the medial surface, by a thin layer of tissue called the visceral pleura. The mediastinum and chest wall are lined by the parietal pleura. It helps some students to visualize the arrangement of the pleurae by thinking of a plastic bag, full of lungs, inside a second plastic bag, the two bags being the visceral and parietal pleurae, respectively (Fig. 2.13).

Fig. 2.13 Schematic diagram of the pleurae. It is important to remember that there is no real ‘space’ between the pleurae, just a few millilitres of slippery fluid.

The pleurae secrete a few millilitres of viscous fluid which lubricates them as they rub against each other during breathing, this fluid constitutes a ‘space’ between the pleurae, but it is important to remember that this tiny space is fluid not air filled. Most animals have pleural space, although it is not essential for life. Elephants are said to lack one, and surgeons sometimes fix the lungs to the chest wall in patients with ruptured lungs, thereby obliterating the space.

Pleurisy

Inflammation of the pleura is called pleurisy and may be ‘dry’, where there is no appreciable effusion, or associated with an effusion, which may be of a variety of compositions. The pain of dry pleurisy is the result of the raw plurae moving over each other, and the patient complains of sharp localized pain associated with inspiration or coughing. Dry pleurisy occasionally accompanies pneumonia or carcinoma. Effusions of fluid into the pleural space result from a variety of conditions and can be of sufficient volume to collapse the lungs. If these effusions contain little protein they are known as transudates; if they contain much protein they are called exudates.

The diaphragm and chest wall

The base of the roughly cylindrical container which is the thorax is formed by the diaphragm. This is a sheet of muscle surrounding a large central tendon (Fig. 2.14).

Fig. 2.14 The diaphragm in coronal section. This figure illustrates how far into the chest the diaphragm bulges. This enables it to act very like the piston in a syringe as its muscle fibres shorten when stimulated by the bilateral phrenic nerves.

The diaphragm lies surprisingly high in the thorax, the central tendon being about level with the eighth thoracic vertebra. Muscle fibres attached to the tendon run down obliquely to originate at the xiphisternum (see above), the lower margins of the ribcage and the upper lumbar vertebrae. Innervation of the diaphragm is by the right and left phrenic nerves, each of which serves its half of the diaphragm. The phrenic nerves originate from cervical spinal cord segments C3–C5 (‘C3, 4 and 5 keep the diaphragm alive’), with the major contribution being made by C4. Both nerves run through the thorax in contact with the mediastinum, penetrate the diaphragm, and innervate it from its inferior surface (see Fig. 2.11).

The walls of the thorax are made up of the ribcage (Fig. 2.15), which consists of the sternum anteriorly, to which ribs 1–6 are joined at about 45° by the costal cartilages. At the spinal column the ribs articulate by costovertebral joints which may involve more than one vertebra. Ribs 7–10 are joined by costal cartilage to the ribs above, and ribs 11 and 12 are free-‘floating’ at their anterior end.

Fig. 2.15 The ribcage. This ‘cage’ is much more flexible than prepared specimens or models sometimes suggest. The intercostal muscles stretch between the ribs.

Case 2.1 Structure of the respiratory system: 2

Causes of OSA

In order for efficient gas flow to take place from the mouth to the alveoli, the airways that make up the respiratory system obviously need to be open and patent. The trachea and larger airways are held open by partial rings of cartilage within their walls. The smaller airways and the alveoli are held open by the tension in the lung tissue surrounding them. Above the larynx, the airway is held open by the actions of airway-dilating muscles, including genioglossus and palatopharyngeus. Were it not for the actions of these muscles, the upper airway would collapse, particularly in the supine position. During sleep, the tone in skeletal muscles throughout the body is reduced and this applies equally to the muscles which keep the upper airways patent. It is therefore normal for the upper airway to become narrowed during sleep.

In patients with OSA, the airway narrowing is more pronounced than normal and leads to periods of airway obstruction. There are a number of reasons why this happens, but obesity is the most important. It is thought that in obese patients, the pressure exerted by the fat in the neck tends to cause the airway to collapse. When the tone in the genioglossus and palatopharyngeus is reduced, as during sleep, airway obstruction may result.

The airway may remain obstructed for only a few seconds, or it may be well over a minute before the patient takes his next breath. During this time, the patient may become hypoxic and will begin to make vigorous efforts to try and breathe against the obstructed airway. Furthermore, he will become increasingly aroused from his sleep. Eventually, he regains the tone in his airway-dilating muscles and the airway obstruction is relieved. (Patients do not usually waken.) After the obstruction has been relieved, ventilation resumes and the patient’s sleep deepens. This leads to a reduced tone in the airway-dilating muscles and the cycle starts to repeat itself.

Although obesity is probably the most important factor leading to OSA, there are other predisposing factors. These include anatomical variations predisposing to airway narrowing, such as enlarged tonsils, airway tumours and abnormalities of the mandible. Sedative drugs, including alcohol, may also predispose to sleep apnoea, probably by affecting sleep patterns and by reducing muscle tone. A small number of cases of OSA may be explained by abnormalities of neuromuscular function.

Between the ribs are the three layers of the intercostal muscles:

1. External intercostals, running forward and downward

2. Internal intercostals, at right-angles to the externals, therefore running downward and posteriorly

3. Innermost intercostals, whose fibres run in the same direction as those of the internals.

These muscles are innervated by intercostal nerves from the anterior primary rami of spinal cord segments T1–T11.

Many muscles which do not have a primary role in respiration have their origins on the thorax. They move the head and neck and the upper limbs, for example. These muscles can be enlisted to aid breathing and are therefore called accessory muscles of respiration. The majority of these muscles aid inspiration, with only the flexors of the spine and the muscles of the anterior abdominal wall aiding expiration. Nevertheless, because of the mechanical advantage the accessory expiratory muscles have over the inspiratory muscles, we can blow out more powerfully than we can breathe in.

How breathing is brought about

Anyone who has sucked up fluid with a syringe has demonstrated how inspiration takes place. Before we go into the details of how the two processes are similar, we need to establish two very important facts:

1. The lungs do not have muscles that contribute to breathing: the small amount of muscle they contain controls the diameter of the airways.

2. Air will only flow from a region of high pressure to a region of low pressure. In inspiration the pressure in the elastic alveoli is made low by stretching them by reducing the pressure around them by expanding the chest. Air is thus sucked into the lungs. During expiration pressure in the lungs is increased by decreasing the size of the chest, thereby compressing the gas in the lungs.

The reduction in pressure around the lungs which brings about inspiration is mainly the result of activity in the phrenic nerves, causing the diaphragm to flatten and descend in the chest like a plunger in a syringe. This draws air into the chest. In quiet breathing inspiration is the only active part of breathing; expiration is largely passive and is the result of the elastic recoil of the lungs pulling them and the diaphragm back into their resting position – something like a balloon deflating when its neck is released.

The central tendon of the diaphragm moves 1–2 cm during breathing at rest, but can move up to about 10 cm during vigorous breathing. Movement of the diaphragm normally accounts for about 75% of the volume of breathing, but is not essential for life: if the diaphragm is paralysed, other respiratory muscles can take over to a large degree. In quiet breathing only some (and not always the same) diaphragmatic muscle fibres contract with each inspiration. This may explain why we rarely suffer from fatigue of the diaphragm.

If we liken the diaphragm to the plunger of a syringe, the ribs can be likened to its walls. The action of the intercostal muscles on the ribs (mainly the second to the tenth) can, however, alter the diameter of the chest and so actively draw air into and expel it from the lungs. This is largely because the ribs are set at an angle, sloping down from the horizontal, and are capable of being raised and lowered (see Fig. 2.14).

The external intercostal muscles cause two types of movement during inspiration:

1. ‘Pump-handle’ movements, in which the anterior end of each rib is elevated like the action of an old-fashioned water pump.

2. ‘Bucket-handle’ movements, in which the diameter of the chest increases, each rib on either side acting like the raising of the handle of a bucket from the horizontal position.

Both these types of action increase the diameter of the chest and thus draw air into the lungs by reducing the pressure in the chest. Not only do the external intercostal muscles help to bring about this reduction in pressure, but by stiffening the chest wall during inspiration they prevent a ‘sucking-in’ of the chest (just as you can suck in your cheeks) that would take place if they did not contract. The action of the intercostal muscles accounts for about 25% of maximum voluntary ventilation. The importance of the ribs and intercostal muscles to breathing is seen in patients whose ribs are broken and who exhibit what is known as ‘flail chest’ in which the chest wall moves in during inspiration and out during expiration.

Although expiration is largely passive during quiet breathing (resulting from the elastic recoil of the lungs–like a balloon collapsing) expiratory muscles can contract actively during high levels of breathing or if the airways are obstructed by disease. Under these conditions the abdominal muscles are the most important muscles of expiration. By squeezing the contents of the abdomen up against the diaphragm they force it up into the chest, thereby expelling air from the lungs. These abdominal muscles are especially active during a cough or a sneeze, as will be apparent if you press your fingers into your abdomen and cough. The internal and innermost intercostal muscles, like the external intercostals, occupy the spaces between the ribs and are innervated by segmental nerves. They pull the ribs down, reduce the diameter of the chest, and so contribute to expiration. Like the external intercostals, they reinforce the spaces between the ribs and prevent the chest from bulging out during expiration. The changes in size and shape of the chest brought about by the activity of the diaphragm, intercostals and accessory muscles are transmitted to the outer surface of the lungs. Because the lungs are so flexible, any change in pressure on their surface is rapidly transmitted to the air within the alveoli. This does not mean that the actual pressure in the fluid between the layers of pleura that form the covering of the lungs and the lining of the chest is the same as the pressure in the alveoli (see Chapter 5): in fact, it is important for the student to realize that they are very different.

Embryology

A knowledge of the embryological origins of anatomical structures is often of use in understanding their physiological function, and many clinical situations. For example, the phenomenon of referred pain can be explained on the basis of common embryological origins of structures. Development of the fetal and neonatal lung can explain many differences in the function of the immature and the adult lung.

Prematurity, particularly with birthweights less than 2500 g, can result in respiratory distress in the infant because of the immaturity of type II pneumocytes, which produce surfactant (pp. 18, 36). This respiratory distress syndrome, also called hyaline membrane disease, develops within minutes or hours of birth and is characterized by high breathing rates requiring great effort owing to the reduced compliance of the lungs. When premature delivery of an infant is threatened its ability to secrete surfactant is estimated by measuring the ratio of lecithin to sphingomyelin in its amniotic fluid. If necessary, the activity of the type II pneumocytes can be enhanced by the administration of corticosteroids, and after birth exogenous surfactant can be administered as an aerosol. Nevertheless, mortality can be as high as 40%, which demonstrates how, even in the full-term baby, the development of the respiratory system is only just sufficiently complete.

In the 4-week-old human embryo the beginnings of the respiratory system are first seen as an outpouching, the laryngotracheal bud, on the ventral surface of the endoderm of the digestive tract (Fig. 2.16). As the bud elongates the proximal portion forms the trachea and the distal end bifurcates to form first the two main bronchi and then the more distal parts of the bronchial tree, eventually forming a limited number of alveoli. The whole of the epithelium lining the entire respiratory tract is therefore derived from endoderm. The cartilage, muscle and connective tissue which make up much of the structure of the lungs develop from embryonic mesoderm that becomes associated with the laryngotracheal bud.

Fig. 2.16 Lateral view of a 4-week human embryo. The laryngotracheal bud is beginning to divide to form the two lungs.

The lung undergoes five overlapping phases of development:

• microvascular maturation.

In the pseudoglandular phase, which lasts from the fifth to the 17th week, the lung resembles a primitive compound gland, with the airways down to terminal bronchioles becoming visible. From week 16 to week 26 is the canalicular stage, with the airway generations of the future respiratory regions being formed. At the same time the airways are pushing through the surrounding mesenchyme, picking up a sleeve of capillaries which forms a local network that grows with the airway. From week 25 to birth the future alveolar ducts and alveolar sacs are produced by growth and branching of the irregularly shaped saccules at the ends of the prospective respiratory bronchioles. Although alveolar formation has started as early as week 36 of gestation, at birth there are only 50 million alveoli present, compared with 300 million in the adult lung. Alveolization continues for about 2 years after birth. The maturation of the microvasculature of the lung parallels alveolization during the first 2 years of independent life. From then onwards, the lung compartments grow in proportion to each other and to body weight.

Summary 3

• There are no muscles in the lungs that bring about breathing.

• Inspiration is brought about mainly by the diaphragm descending, like the plunger in a syringe.

• Expiration is largely passive due to the elasticity of the lungs, like a balloon deflating.

• Active expiration, as in exercise, involves the muscles of the abdomen.

Air-conditioning

The characteristics of all respiratory surfaces do not lead to their physical robustness (thin walls, vascular, moist). Therefore, it is of evolutionary advantage to have the respiratory surface of the lungs protected from damage by the air, or anything in the air, that must be moved over them during respiration. Even under the most congenial conditions the air around us is cold and dry compared with the respiratory surface of the lungs.

Case 2.1 Structure of the respiratory system: 3

Signs and symptoms of OSA

Often, the first person to complain about a patient’s OSA is his or her spouse! OSA is invariably associated with loud snoring as the airway becomes narrowed and this combined with the cycles of obstruction and arousal can lead to a very poor night’s sleep for anyone in the same room as the patient. By the time a patient presents for treatment, their spouse has often resorted to sleeping alone.

The main symptom that the patient complains of is daytime drowsiness. Because their sleep patterns are so disrupted by cycles of apnoea and arousal, these patients are very tired and sleepy during the day. This somnolence may begin to impinge upon the patient’s work and home life as their ability to concentrate for long periods of time begins to diminish. At worst, the patient may have a tendency to lose concentration or even fall asleep at the wheel of their car – motor accidents are more common in patients with OSA.

Other symptoms that the patient may complain of include morning headaches and night sweating and relatives may notice personality changes. For reasons that are not fully understood, patients often complain of having to get up to urinate during the night, sometimes on a few occasions.

Treatment is aimed at reducing the incidence of airway obstruction. The patient is advised to lose weight and to limit alcohol consumption, particularly before retiring to bed.

The most effective form of treatment, and the one tried by Mr Sinclair, is nasal continuous positive airway pressure (NCPAP). The patient wears the small mask strapped over his nose at night. The mask forms an airtight seal around the patient’s nose. A continuous positive pressure, generated by a small pump, is applied to the mask. This pressure is transmitted to the upper airways and tends to prevent them from collapsing.

Other treatments are available – a surgical treatment of the condition that was at one time popular is the uvulopalatopharyngoplasty (UPPP). This operation involves removing the uvula and part of the soft palate. It has only a limited success rate and is associated with complications including fluid refluxing into the nose during drinking. It is therefore infrequently performed today.

Heat and water

Because temperature and water vapour gradients between mucosa and inspired air are greatest in the nose and upper airways, these regions carry a large portion of the air-conditioning burden. This burden is, however, shared with the lower airways. During nose breathing at rest air transit through the nose takes < 0.1 s. During that time temperature is raised (if in comfortable room air) from 20°C to 31°C by the time the air leaves the internal nares and to 35°C by the time it reaches the mid trachea. Humidification takes place equally rapidly, inspired air being close to saturation by the time it reaches the pharynx. Humidification of inspired air places a thermal demand on the body because of the high latent heat of vaporization of water. Five times as much heat is used to vaporize water to saturate inspired air than is used to warm that air. The air-conditioning process is a metabolic ‘expense’, and up to 40% of this cost is recovered from the expired air which warms and moistens the nasal mucosa as we breathe out. Desert animals such as camels and gerbils have highly developed turbinate systems in their noses which recover more heat and water than do ours.

This countercurrent exchange of heat and water in our nose is well demonstrated under cold conditions, when the mucosa of the nose is much colder than the exhaled air from deep in the lungs. Under these conditions sufficient water may condense to form a drop on the end of the nose. This is a purely natural physical phenomenon, not ‘a cold’ or other pathological condition.

At rest most people breathe through their nose, although 15% of the population are habitual mouth breathers. We all resort to mouth breathing during heavy exercise. The mouth is surprisingly good at air-conditioning, and by the time the air reaches the glottis conditions are very similar whether you are breathing through nose or mouth. The disadvantage of mouth breathing is in expiration, when much less heat and water is recovered. We have all experienced the discomfort of the dry mouth which often accompanies the nasal obstruction of a cold.

Particles and vapours

The respiratory system is threatened by many of the particles and chemical vapours in the air. The upper and conducting airways are much more robust than the respiratory surface, and they bear the brunt of protecting the respiratory surface by filtering these particles and vapours out of the inspired air.

Particles must be relatively small to penetrate the respiratory tract to any depth, and it is their size and shape that determine where they land. Where they land determines how they are dealt with.

An aerosol is a cloud of particles or droplets that remains stable and suspended in the air for some time. Because the volume (and hence the mass) of a drop is related to the cube of its diameter and its surface area is related to the square of its diameter, large drops fall faster than smaller ones. A shower of rain falls to the ground; a mist remains suspended for some time (Stoke’s Law tells us that the terminal velocity of a falling sphere is proportional to the square of its radius). Scientists interested in the way aerosols behave in the lungs often convert the weight and shape of the particles into the size of the aerodynamically equivalent spheres. The mass median diameter of an aerosol is the diameter about which 50% of the total particle mass resides. The mass median aerodynamic diameter (MMAD) is the product of the mass median diameter and the square root of the particle density. Using this system we see 95% of particles > 5 mm MMAD impact on the walls of the nose and pharynx, where they are trapped by the sticky mucus. This impaction is the result of turbulence and the particles’ momentum throwing them out of the airstream, when they rapidly change direction. In our noses the mucus that has trapped the dust is wafted to the pharynx by cilia. It is then swallowed. In dogs the cilia beat toward the outside and this contributes to the wet nose of a healthy dog. Slightly smaller particles (1–5 mm) survive the twists and turbulence of the upper airways and are removed by sedimentation in the small airways. Sedimentation is the settling of particles’ under gravity, and this slow process is only effective in the small airways because their diameter is so small that the particles have only a little way to fall. Small though they are, these particles are too massive to be much affected by the buffeting of the gas molecules around them that constitutes the phenomenon of diffusion. Particles which reach the wall of the small airways are trapped in the mucus there and travel up the mucociliary escalator at a rate of about 2 mm s⁻¹ to the pharynx in considerable amounts, to be swallowed. The mucus blanket which traps the particles is 5–10 mm thick and in two layers. The outer gel layer rests on a less viscous layer in which the cilia beat toward the mouth at a frequency of about 20 Hz.

The smallest particles of all (<0.1 mm) are deposited by diffusion of gas molecules producing Brownian motion. The particles are ‘jostled’ until they bump into the wall of a small airway or alveolus. In this region particles are stuck to the walls by surface tension because there is no secretion of mucus. They are also beyond the end of the ciliary escalator. In the alveolar region amoeboid macrophages (Fig. 2.17) engulf particles and carry them to the escalator, or take them into the blood or lymph. When the dust load is large the macrophages dump their load around the respiratory, bronchioles, and any pathologist from a coal-mining area will have seen the black ‘halos’ so formed. Bacteria are particularly susceptible to the attentions of macrophages, which kill them with enzymes and oxygen-based free radicals (see Metabolic activity, p. 26) or transport them out of the lungs. The activities of these phagocytic cells ensure that the alveolar region of the lung is effectively sterile.

Fig. 2.17 Alveolar macrophage. Formed from monocytes produced in the bone marrow, these phagocytic cells contain enzymes destructive to microorganisms. These enzymes can produce emphysema in patients deficient in the protective protein α₁-antitrypsin. M, macrophage; C, septal capillary; P₁, type 1 pneumocyte; AP, alveolar pore; BM, basement membrane; Ly, lysosomes; L, lipid droplets. (Source: Young and Heath 2000.)

The free radicals and proteases produced by macrophages to deal with foreign material have the potential to damage the lung itself; how these dangerous substances are neutralized is described below (Metabolic activity, p. 36).

The influence of impaction, sedimentation and diffusion on particles of different aerodynamic diameters is illustrated in Figure 2.18.

Fig. 2.18 Deposition of particles in the lung. Notice that the aerodynamic diameter is a log scale and that there is a point at about 0.5 mm diameter where deposition is minimal.

The majority of particles of 0.5 mm aerodynamic diameter are not deposited: they ride the airflow into the lungs and back out again with expiration. Figure 2.18 represents the case during quiet breathing. Treatment of disease with therapeutic aerosols requires slow deep breathing to ensure deep penetration and sufficient time for diffusion. The increased ventilation of exercise enhances impaction and the danger of heavy work in dusty environments.

Particles account for only a small fraction by weight of the pollutants we breathe (Fig. 2.19).