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Normal physiology of the respiratory system 

Normal physiology of the respiratory system
Normal physiology of the respiratory system

Göran Hedenstierna

and João Batista Borges

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date: 27 November 2020

Key points

  • Functional residual capacity (FRC) is lowered in supine position and reduced further by anaesthesia. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) goes with very low lung volume, frequently below 1 L.

  • Compliance of the lung is increased in emphysema, but reduced in lung fibrosis and during anaesthesia, the latter because of reduced ventilated lung volume. ALI/ARDS are found with very low lung compliance and frequently with low chest wall compliance.

  • Airway resistance is increased in obstructive lung disease, but also during anaesthesia and in ALI/ARDS because of reduced lung volume with decreased airway dimensions.

  • Inspired air goes mainly to lower, dependent lung regions, but a shift to upper lung can be seen during anaesthesia and in ALI/ARDS, because of low lung volume promoting airway closure in dependent regions.

  • Lung blood flow goes mainly to dependent lung regions and more so with increase in alveolar gas pressure. Besides a gravitational perfusion distribution there is also a non-gravitational perfusion inhomogeneity that may possibly exceed gravitational inhomogeneity.

Lung volumes and ventilation

The lungs contain 2–300 million alveoli with a total surface area, for gas exchange, of approximately 140 m2. The alveoli are reached via 23 generations of airways with a rapidly increasing total surface area from 2.5 cm2 at the trachea to 70 cm2 in the 14th generation that enters the acinus, to 0.8 m2 (8000 cm2) in the 23rd generation [1]‌. Gas flow velocity decreases as the area increases. For an ordinary breath, the average velocity of gas in the trachea is around 0.7 m/sec, but at the alveolar surface it is no higher than 0.001 mm/sec (Fig. 71.1, left part). This is much slower than the diffusion rate of O2 and CO2. Transport of O2 and CO2 is therefore accomplished by diffusion in the peripheral airways and in the alveoli, not by convective flow.

Fig. 71.1 The airway tree from generation 1 (trachea) to generation 23 (terminal bronchioli) (left panel), the vertical distributions of ventilation and blood flow (upper right) and airway closure and alveolar collapse (lower right).

Fig. 71.1 The airway tree from generation 1 (trachea) to generation 23 (terminal bronchioli) (left panel), the vertical distributions of ventilation and blood flow (upper right) and airway closure and alveolar collapse (lower right).

The gas volume in the lung after a maximum inspiration is called total lung capacity (TLC) and is typically 6–8 L [2]‌. TLC can increase in patients with chronic obstructive pulmonary disease (COPD), and decrease in fibrosis and other restrictive disorders.

Even after a maximum expiratory effort, some air is left in the lung, preventing collapse. This remaining gas volume is called residual volume (RV) and amounts to 2–2.5 L. The maximum volume that can be inspired and expired is called vital capacity (VC), and is around 4–6 L. It is reduced in restrictive lung diseases, frequently before a decrease in RV. What may not be equally clear is that VC is also reduced in obstructive lung disease. This is an effect of the chronic ‘air trapping’ that increases RV, mainly at the expense of VC [2]‌.

The volume in the lungs after an ordinary expiration is called functional residual capacity (FRC) and is approximately 3–4 L [2]‌. It is increased in obstructive lung disease and reduced in restrictive disorders. It is reduced by 0.7–0.8 L when supine compared with an upright position and by another 0.4–0.5 L by anaesthetics, muscle relaxants, and possibly sedatives (lowered muscle tone) [3].

All inspired air does not reach the alveoli. Approximately 100–150 mL will be confined in the airways and does not participate in gas exchange. This ‘anatomical deadspace’ is approximately 30% of tidal volume; that is, the VD/VT ratio is 0.3 [4]‌. The remaining part of ventilation reaches the alveoli and respiratory bronchioles (with some alveoli tapered on the airway wall). Thus, ‘alveolar ventilation’ is around 5 L/min, similar to cardiac output, which is also approximately 5 L/min. Accordingly, the overall alveolar ventilation-perfusion ratio is 1.

Ventilation through a mouthpiece, facemask, or tubings adds an apparatus deadspace of 25 to a few hundred millilitres. Intubation of the trachea reduces anatomic dead space almost to half, 70–80 mL. Pulmonary emboli and obstructive lung disease increase deadspace by ventilation of alveoli that are not perfused or ventilated in excess of perfusion (‘alveolar dead space’). The sum of the anatomic and alveolar dead spaces is called ‘physiological dead space’.

Compliance of the respiratory system

The lung recoils like an elastic rubber balloon. The pressure needed to keep the lung inflated at a certain volume is pleural minus alveolar pressure, or ‘transpulmonary pressure’ (Ptp) [5]‌. Oesophageal pressure (Pes) is for technical and safety reasons substituted for pleural pressure. A change in lung volume (Δ‎V) divided by the concomitant change in Ptp gives lung compliance. Normally, it is around 0.2–0.3 L/cmH2O (2–3 L/kPa). It is increased in emphysema, but reduced in fibrotic lung disease and during anaesthesia, the latter being a consequence of reduced ventilated lung volume [6]. It can be markedly reduced in acute lung injury (ALI, ARDS) [7]. If a lung is resected, the measured compliance is reduced, despite the fact that the remaining lung tissue is unaltered (a compensatory expansion may occur).

The chest wall also exerts elastic impedance to breathing that goes undetected during spontaneous breathing because the chest wall is part of the pump itself. During muscle relaxation, on the other hand, the separate compliances of the lung and the chest wall can be measured by dividing Δ‎V with Δ‎Ptp (lung) and Δ‎V with Δ‎Pes (chest wall). Compliance of the chest wall is approximately the same magnitude as compliance of the lungs, around 0.2 L/cmH2O. It may go down in obesity and in ALI/ARDS, especially in so called ‘extra-pulmonary ARDS’ [7]‌.

Resistance of the respiratory system

Pressure is required to force gas flow (V’) through the airways during respiration. In addition, movement of lung tissue and chest wall during inspiration and expiration exerts resistance (R) [8]‌. In the mechanically-ventilated subject airway, lung tissue, and chest wall resistances are mostly measured together as Rtot = (peak airway–end-inspirtory airway pressure):V’, but techniques are available for recording of the individual components.

In larger airways, gas flow is turbulent and proportional to the square of the pressure. In smaller airways, flow is laminar and is linearly related to pressure. Thus, most of the energy or pressure involved in creating flow of gas is expended on overcoming resistance in the larger airways [8]‌. Only about 20% of the measured airway resistance, in a normal subject, is located in the small bronchi [9].

Airflow resistance is normally around 1 cmH2O/L/sec. Since airway dimensions vary with lung volume, resistance goes up with decrease in volume. At RV resistance may be 4–6 cmH2O/L/sec, similar to that in moderate asthma [10]. Breathing through a size 8 endotracheal tube causes a resistance of 5 cmH2O/L/sec at a flow of 1 L/sec and size 7 tube increases resistance to 8 cmH2O/L/sec [11].

The resistance of lung tissue and the chest wall has been studied to a lesser extent. Lung tissue resistance amounts to around 1 cmH2O/L/sec in normal cases, but can be increased three- to four-fold in chronic lung disease. Even less has been studied regarding chest wall resistance. However, the sum of lung tissue and chest wall resistance is markedly increased in acute respiratory failure, demanding mechanical ventilation [12].

Distribution of inspired gas

During quiet breathing, inspired air goes mainly to the lower, dependent regions—basal, diaphragmatic areas in the upright or sitting position, dorsal units in the supine position, and left lung in left lateral position [9]‌. The reason for this seemingly gravitational orientation of something as light as gas is the combined effect of the curved pressure–volume relationship of the lung tissue and the increasing pleural pressure down the lung (Fig. 71.1, upper right).

With increasing flow rate, more inspired air goes to the upper, non-dependent lung regions [13]. This is because the airways are more expanded in the upper than in the lower regions and resistance becomes increasingly important with increasing gas flow.

Airway closure

Airways become narrower during expiration, as can be inferred from the previous discussion. If the expiration is deep enough, airways in dependent regions will eventually close. The volume above RV at which airways begin to close during expiration is called the closing volume (CV), and the sum of RV and CV is called closing capacity (CC)[14]. Airway closure is a normal physiological phenomenon and is caused by increasing pleural pressure during expiration. When pleural pressure exceeds atmospheric pressure it will compress the airway and close it. Because pleural pressure is higher in dependent regions than higher up, closure of airways begins in the bottom of the lung. With increasing age, pleural pressure is ‘positive’ at higher lung volume, and at an age of 65–70 years, airway closure may occur above FRC [14].

Airway closure plays an even greater role in the supine position, because FRC is reduced, whereas CC is not. Closure of airways may occur above FRC, even at an age of 45–50 years. Airway closure is more common during anaesthesia because of the decrease in FRC, whereas CC seems to be unaltered [6]‌. If the anaesthetized patient is ventilated with a high concentration of O2, the alveoli will collapse behind continuously closed airways, thus producing atelectasis (see Fig. 71.1, lower right) [6]. Airway closure is also more common in obstructive lung disease [14].

Diffusion of gas

Oxygen diffuses passively from the alveolar gas phase into plasma and red cells, where it binds to haemoglobin. Carbon dioxide diffuses in the opposite direction, from plasma to the alveoli. The amount that can diffuse over the membranes for a given period is determined by:

  • The surface area available for diffusion.

  • The thickness of the membranes.

  • The pressure difference of the gas across the barrier.

  • The molecular weight of the gas.

  • The solubility of the gas in the tissues that it has to traverse.

Diffusion limitation is of importance in lung fibrosis and in emphysema, but seems not to be an important issue in anaesthesia and intensive care. For further details, see ref. [15].

Pulmonary perfusion: pressure–flow relationship

The pulmonary circulation is a low-pressure system with a pulmonary artery pressure of approximately 20/8 mmHg. The lower pressure is an effect of larger vascular diameter and shorter distance of the pulmonary vessels than the systemic ones. As a consequence of the lower resistance, pulmonary capillary blood flow is pulsatile, contrary to the steady flow in systemic capillaries [16]. Another consequence of the low pressure is that the capillary and alveolar walls can be made very thin without causing any leakage of plasma, and this facilitates diffusion of O2 and CO2, but also of oedema formation if the vascular pressure goes up.

Distribution of lung blood flow

The ‘classical’ model of lung blood flow distribution is related to gravity [17]. Pulmonary artery pressure (PAP) increases down the lung by 1 cmH2O/cm distance. This causes a PAP difference between the upper and lower regions of 11–15 mmHg, depending on the height of the lung. There is thus less driving pressure to the top of the lung. If alveolar pressure is increased, as during positive-pressure ventilation, it may exceed PAP and compress the pulmonary capillaries and prevent blood flow (so called zone I). Further down, arterial pressure exceeds alveolar pressure and blood flow will be established. The increasing PAP down the lung and the constant alveolar pressure increase blood flow down this ‘zone II’. Further down the lung, both arterial and venous pressures exceed that in the alveoli (zone III). Despite similar increase in arterial and venous pressure, perfusion increases down this zone, by increasing dilation of vessels. In the bottom of the lung perfusion decreases, presumably because of increasing interstitial pressure (zone IV; Fig. 71.1, upper right).

There is also accumulating evidence that there are morphological or functional differences (or both) between lung vessels that—and perhaps more importantly than gravity—determine blood flow distribution with more inhomogeneity in a horizontal than vertical plane (‘fractal distribution’) [18].

Hypoxic pulmonary vasoconstriction

Hypoxic pulmonary vasoconstriction (HPV) reduces blood flow in hypoxic lung regions. A major stimulus for HPV is low alveolar oxygen tension, whether caused by hypoventilation or by breathing gas with a low PO2. The stimulus of mixed venous PO2 is much weaker [19]. The strength of the constriction is also dependent on the size of the lung segment exposed to the hypoxia, being stronger the smaller the region is.

Chronic lung disease with hypoxaemia also causes HPV, but the slow progress of the disease allows time for remodelling of the pulmonary vascular wall, with thickening of the wall preventing oedema formation [19].


1. Haefeli-Bleuer B and Weibel ER. (1988). Morphometry of the human pulmonary acinus. Anatomical Record, 220, 401–14.Find this resource:

2. Quanjer PH, Tammeling GJ, Cotes JE, et al. (1993). Lung volumes and forced ventilatory flows. Report Working Party ‘Standardization of Lung Function Tests.’ European Community for Steel and Coal. European Respiratory Journal Supplement, 16, 5–40.Find this resource:

3. Wahba RWM. (1991). Perioperative functional residual capacity. Canadian Journal of Anaesthesia, 38, 384–400.Find this resource:

4. Astrom E, Niklason L, Drefeldt B, et al. (2000). Partitioning of dead space—a method and reference values in the awake human. European Respiratory Journal, 16, 659–64.Find this resource:

5. Grassino AE and Roussos C. (1997). Static properties of the lung and chest wall. In: Crystal RG, West JB, Weibel ER, and Barnes PJ (eds) The Lung: Scientific Foundations, 2nd edn, pp. 1187–202. Philadelphia: Lippincott-Raven.Find this resource:

6. Hedenstierna G, Edmark L. (2005). The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Medicine, 31, 1327–35.Find this resource:

7. De Chazal I and Hubmayr RD. (2003). Novel aspects of pulmonary mechanics in intensive care. British Journal of Anaesthesia, 91, 81–91.Find this resource:

8. Pedley TJ and Kamm RD. (1997). Dynamics of gas flow and pressure-flow relationships. In: Crystal RG, West JB, Weibel ER, Barnes PJ (eds) The Lung: Scientific Foundations, 2nd edn, pp. 1365–80. Philadelphia: Lippincott-Raven.Find this resource:

9. Milic Emili J. (2005). Ventilation distribution. In: Hammid Q, Shannon J, Martin J (eds) Physiologic Bases of Respiratory Disease, pp. 131–41. Hamilton, Ontario: BC Decker.Find this resource:

10. Jonson B. (1970). Pulmonary mechanics in normal men studied with the flow regulator method. Scandinavian Journal of Clinical and Laboratory Investigations, 25, 363–73.Find this resource:

11. Holst M, Striem J, and Hedenstierna G. (1990). Errors in tracheal pressure recording in patients with a tracheostomy tube—a model study. Intensive Care Medicine, 16, 384–9.Find this resource:

12. Tantucci C, Corbeil C, Chasse M, et al. (1992). Flow and volume dependence of respiratory system flow resistance in patients with adult respiratory-distress syndrome. American Reviews of Respiratory Diseases, 145, 355–60.Find this resource:

13. Bake B, Wood L, Murphy B, et al. (1974). Effect of inspiratory flow-rate on regional distribution of inspired gas. Journal of Applied Physiology, 37, 8–17.Find this resource:

14. Milic-Emili J, Torchio R, and D’Angelo E. (2007). Closing volume: a reappraisal (1967–2007). European Journal of Applied Physiology, 99, 567–83.Find this resource:

15. Hughes JMB and Bates DV. (2003). Historical review: the carbon monoxide diffusing capacity (Dlco) and its membrane (D-M) and red cell (Theta.Vc) components. Respiratory Physiology & Neurobiology, 138, 115–42.Find this resource:

16. Dawson CA and Linehan JH. (1997). Dynamics of blood flow and pressure-flow relationships. In: Crystal RG, West JB, Weibel ER, and Barnes PJ (eds) The Lung: Scientific Foundations, 2nd edn, pp. 1503–22. Philadelphia: Lippincott-Raven.Find this resource:

17. Hughes M and West JB. (2008). Gravity is the major factor determining the distribution of blood flow in the human lung. Journal of Applied Physiology, 104, 1531–3.Find this resource:

18. Glenny R. (2008). Gravity is not the major factor determining the distribution of blood flow in the human lung. Journal of Applied Physiology, 104: 1533–6.Find this resource:

19. Sylvester JT, Shimoda, LA, Aaronson, PI, and Ward Jeremy PT. (2012). Hypoxic pulmonary vasoconstriction. Physiological Reviews 92, 367–520.Find this resource: