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How We Came to Have Lungs and How Our Understanding of Lung Function has Developed

This chapter describes how the theory and practice of lung function testing have reached their present state of development and gives pointers to the future.

CHAPTER MENU

1. 1.1 The Gaseous Environment
2. 1.2 Functional Evolution of the Lung
3. 1.3 Early Studies of Lung Function
4. 1.4 The Past 350 Years
5. 1.5 Practical Assessment of Lung Function
6. 1.6 The Position Today
7. 1.7 Future Prospects
8. References

1.1 The Gaseous Environment

The basis of respiratory physiology is Claude Bernard's concept of a 'milieu interieur' that remains constant and stable despite changes in the environment. However, the two are not independent since life on Earth has evolved symbiotically with changes in Earth's atmosphere and this process is continuing. At first, the composition of the atmosphere was determined by physical processes, and then by biological ones. Now changes in the composition of air are being driven by man's own actions. It remains to be seen how and to what extent the system will adapt.

Initially the atmosphere was mainly nitrogen. Then as the Earth cooled, carbon dioxide (CO2) was formed by chemical reactions beneath the Earth's crust and released by volcanic activity. Some of the gas was taken up by combination with minerals and deposited as sediment at the bottom of the oceans. Oxygen was released, but immediately combined with iron and other elements, and so the atmospheric concentration was very low [1, 2]. Subsequently, the concentration of oxygen increased as a result of biological activity [3]. A hypothesis as to how this happened was proposed by Lovelock [4], whose concept of the living Earth (Gaia) is on a par with evolution as one of the formative influences of our time.

Free oxygen first appeared some 3.5 × 109 years ago, coincidentally with the development of organisms capable of photosynthesis. The organisms multiplied and their growth reduced significantly the atmospheric concentration of CO2. Some organisms (methanogens) developed an ability to form free methane gas. The methane was liberated into the atmosphere, where it shielded the Earth's surface from ultraviolet light. The shielding allowed ammonia gas to accumulate and this provided a substrate for the growth of photosynthesising organisms; as a result, at the beginning of the Proterozoic era some 2.3 × 109 years ago, the atmospheric concentration of oxygen began to rise. By geological standards the increase was rapid, from 0.1% to 1% over about 1 million years (Figure 1.1).

When the ambient oxygen concentration reached 0.2%, aerobic organisms became abundant in the surface layers of lakes and oceans; at 2%, life began to move onto the land. A concentration of 3% may have been attained some 1.99 × 109 years ago. At 10% photosynthesis was at its peak; this further raised the concentration of oxygen and lowered that of CO2. The changes reduced the available substrate (CO2) and increased the formation of hydrogen peroxide, superoxide ions, and atomic oxygen that were potentially lethal to cells. Photosynthesis was reduced in consequence. With other factors, the balance between promotion and inhibition of photosynthesis formed a feedback loop that stabilised the atmospheric concentration of oxygen at its present level (21.93%, FIO2 = 0.2193; Chapter 6).

Figure 1.1 Approximate timescale for the evolution of the gaseous environment.

Source: After [4].

The concentration of oxygen stabilised at the start of the Phanerozoic era some 6 × 108 years ago. It led to the evolution of animals with skeletons. Thereafter, the concentration of CO2, and to some extent that of oxygen, appears to have oscillated in response to secondary factors. These included fluctuations in the balance between the relative dominance of plants and animals. Some 5 × 108 years ago the species that were net consumers of oxygen (e.g. bacteria, fungi, and insects) were in the ascendancy and CO2 levels were relatively high. Then, plants that fix CO2 as lignin appeared and the levels fell. The plants led to the evolution of dinosaurs and other animals that could feed off and digest the cellulose. The species flourished and the cycle was reversed. From time to time the sequence was unsettled by dust clouds from meteors and volcanic eruptions. The dust interfered with photosynthesis by obscuring the sun, but up to the present the equilibrium has always been restored.

Currently, the atmosphere is under threat from human activity. Clearance of forests and the replacement of grassland by buildings and roads are reducing the Earth's capacity for photosynthesis. Hence, the amount of CO2 removed from air is falling. Concurrently, the quantity released is increasing because of massive combustion of fossil fuels. As a result, the Earth's temperature is rising and this is increasing the formation of methane gas that could raise the temperature further. However it also has other effects, and so the long-term outcome is unpredictable. In the short term any change in gaseous equilibrium is likely to occur slowly.

In summary, living organisms first appeared in an anaerobic environment that they helped to convert to an aerobic one. Hence they were adapting to the new conditions as they were creating them. On this account, the capacity to tolerate conditions of hypoxia and hypercapnia are part of man's heritage. How this is achieved is described in subsequent chapters. The evolutionary history also indicates the importance of natural protection against oxygen radicals. However, there is only limited evidence for Berken and Marshall's suggestion [1] that the relevant mechanisms emerged during periods of what we would now regard as hyperoxia.

1.2 Functional Evolution of the Lung

Aerobic organisms developed in an aqueous medium where the amount of oxygen is determined by its partial pressure and by the solubility; this is such that the concentration in water is only about one-fortieth of that in air (Table 1.1). By contrast CO2 is highly soluble, so at physiological partial pressures the concentration in water is nearly as great as in air. The differences in solubility have consequences for gas exchange [5].

For fish the problem of obtaining sufficient oxygen was solved by the evolution of the gill system. This organ is ventilated by a large volume of water from which almost all the oxygen is extracted; the blood leaving the bronchial clefts contains oxygen in a concentration equal to that in blood leaving the lung in man. However, the large volume of water flowing over the gill takes with it much of the CO2 in solution and this lowers the CO2 tension in the blood leaving the gill to less than 0.7 kPa (5 mmHg). Mainly on this account the blood pH is relatively high (approximately 8.0 pH units at a temperature of 20 °C). At higher water temperatures the pH falls to approach that in the blood of man. Concurrently, the solubility of oxygen in water delivered to the gill clefts is reduced.

Table 1.1 Atmospheric concentrations and solubility in water of oxygen and carbon dioxide.

a Solubility in blood plasma is approximately 10% less.

atm., atmosphere; TPD, standard temperature and pressure dry.

In hot climates a high ambient temperature might cause streams to dry up, leaving any fish stranded. To meet this hazard some fish developed lung-like pouches in the back of the pharynx; they also developed primitive limbs with which to crawl along streambeds in search of water. For this type of existence a gill for the exchange of CO2 and a primitive lung for exchanging oxygen formed a life-saving combination. The lung was further developed in reptiles. In birds the pouches were adapted as reservoirs from which air was pumped in a cross-current manner through parabronchi; these supplied air to the gas exchange zones where the whole of the surface was lined with capillaries. This arrangement resulted in a very compact lung with a high capacity to transfer gas. The amphibians developed in a different way by shedding their scales to leave a soft vascular skin; this replaced the gill as a means of exchanging CO2 with the surrounding water. Somewhere between these diverging species emerged the primitive mammals and eventually man.

1.3 Early Studies of Lung Function

Erasistratus (c. 280 BCE) and Galen (129-201) (see Footnote 1.1) demonstrated the role of the diaphragm as a muscle of respiration, the origin and function of the phrenic nerve, and the function of the intercostal...