Airways expand as lung volume is increased, and at full inspiration (total lung capacity, TLC) they are 30-40% larger in calibre than at full expiration (residual volume, RV). In chronic obstructive pulmonary disease (COPD) the small airways are narrowed and this can be partially compensated by breathing at a larger lung volume.
Control of airway tone
Bronchomotor tone is maintained by vagal efferent nerves and, even in a normal subject, is reduced by atropine or β-adrenoceptor agonists. Adrenoceptors on the surface of bronchial muscles respond to circulating catecholamines; there is no direct sympathetic innervation. Airway tone shows a circadian rhythm, which is greatest at 04.00 and lowest in the mid-afternoon. Tone can be increased transiently by inhaled stimuli acting on epithelial nerve endings, which trigger reflex bronchoconstriction via the vagus. These stimuli include cigarette smoke, solvents, inert dust and cold air; airway responsiveness to these increases following respiratory tract infections even in healthy subjects. In asthma, the airways are very irritable and as the circadian rhythm remains the same, asthmatic symptoms are usually worse in the early morning.
Airflow
Movement of air through the airways results from a difference between the pressure in the alveoli and the atmospheric pressure; alveolar pressure is positive in expiration and negative in inspiration. During quiet breathing the pleural pressure is sub-atmospheric throughout the breathing cycle. With vigorous expiratory efforts (e.g. cough), the central airways are compressed by positive pleural pressures exceeding 10 kPa, but the airways do not close completely because the driving pressure for expiratory flow (alveolar pressure) is also increased.
Alveolar pressure (PALV) is equal to the pleural pressure (PPL) plus the elastic recoil pressure (PEL) of the lung.
When there is no airflow (i.e. during a pause in breathing) the tendency of the lungs to collapse (the positive recoil pressure) is exactly balanced by an equivalent negative pleural pressure.
As air flows from the alveoli towards the mouth there is a gradual loss of pressure owing to flow resistance(Fig. 14.7a).
In forced expiration, as mentioned above, the driving pressure raises both the alveolar pressure and the intrapleural pressure. Between the alveolus and the mouth, there is a point (C in Fig. 14.7b) where the airway pressure equals the intrapleural pressure, and the airway collapses. However, this collapse is temporary, as the transient occlusion of the airway results in an increase in pressure behind it (i.e. upstream) and this raises the intra-airway pressure so that the airways open and flow is restored. The airways thus tend to vibrate at this point of 'dynamic collapse'.
The elastic recoil pressure of the lungs decreases with decreasing lung volume and the 'collapse point' moves upstream (i.e. towards the smaller airways - see Fig. 14.7c). Where there is pathological loss of recoil pressure (as in chronic obstructive pulmonary disease, COPD), the 'collapse point' starts even further upstream and causes expiratory flow limitation. The measurement of the forced expiratory volume in 1 second (FEV1) is a useful clinical index of this phenomenon. To compensate, these patients often 'purse their lips' in order to increase airway pressure so that their peripheral airways do not collapse. On inspiration, the intrapleural pressure is always less than the intraluminal pressure within the intrathoracic airways, so there is no limitation to airflow with increasing effort. Inspiratory flow is limited only by the power of the inspiratory muscles.
Flow-volume loops |
In subjects with healthy lungs, effects of flow limitation will not be apparent, since maximal flow rates are rarely achieved even during vigorous exercise. However, in patients with severe COPD, limitation of expiratory flow occurs even during tidal breathing at rest (see Fig. 14.8b). To increase ventilation these patients have to breathe at higher lung volumes and allow more time for expiration which both reduce the tendency for airway collapse. To compensate they increase flow rates during inspiration, where there is relatively less flow limitation.
The measure of the volume that can be forced in from the residual volume in 1 second (FIV1) will always be greater than that which can be forced out from TLC in 1 second (FEV1). Thus, the ratio of FEV1 to FIV1 is below 1. The only exception to this occurs when there is significant obstruction to the airways outside the thorax, such as with a tumour mass in the upper part of the trachea. Under these circumstances expiratory airway narrowing is prevented by the tracheal resistance (a situation similar to pursing the lips) and expiratory airflow becomes more effort-dependent. During forced inspiration this same resistance causes such negative intraluminal pressure that the trachea is compressed by the surrounding atmospheric pressure.
Inspiratory flow thus becomes less effort-dependent, and the ratio of FEV1 to FIV1 becomes greater than 1. This phenomenon, and the characteristic flow-volume loop, is used to diagnose extrathoracic airways obstruction (Fig. 14.8c).
When obstruction occurs in large airways within the thorax (lower end of trachea and main bronchi), expiratory flow is impaired more than inspiratory flow but a characteristic plateau to expiratory flow is seen (Fig. 14.8d).
Ventilation and perfusion relationships
For efficient gas exchange there must be a match between ventilation of the alveoli ([Vdot]A) and their perfusion ([Qdot]). There is a wide variation in the [Vdot]A/[Qdot] ratio throughout both normal and diseased lung. In the normal lung the extreme relationships between alveolar ventilation and perfusion are:
- ventilation with reduced perfusion (physiological deadspace)
- perfusion with reduced ventilation (physiological shunting).
An increased physiological shunt results in arterial hypoxaemia. The effects of an increased physiological deadspace can usually be overcome by a compensatory increase in the ventilation of normally perfused alveoli. In advanced disease this compensation cannot occur, leading to increased alveolar and arterial Pco2, together with hypoxaemia which cannot be compensated by increasing ventilation.
Hypoxaemia occurs more readily than hypercapnia because of the different ways in which oxygen and carbon dioxide are carried in the blood. Carbon dioxide can be considered to be in simple solution in the plasma, the volume carried being proportional to the partial pressure. Oxygen is carried in chemical combination with haemoglobin in the red blood cells, and the relationship between the volume carried and the partial pressure is not linear (see Fig. 15.5, p. 960). Alveolar hyperventilation reduces the alveolar Pco2 and diffusion leads to a proportional fall in the carbon dioxide content of the blood. However, as the haemoglobin is already saturated with oxygen, there is no significant increase in the blood oxygen content as a result of increasing the alveolar Po2 through hyperventilation. The hypoxaemia of even a small amount of physiological shunting cannot therefore be compensated for by hyperventilation.
In individuals who have mild disease of the lung causing slight [Vdot]A/[Qdot] mismatch, the Pao2 and Paco2 may still be normal. Increasing the requirements for gas exchange by exercise will widen the [Vdot]A/[Qdot] mismatch and the Pao2 will fall. [Vdot]A/[Qdot] mismatch is by far the most common cause of arterial hypoxaemia.
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