This chapter is vaguely relevant to Section F3(x) from the 2023 CICM Primary Syllabus, which expects the exam candidates to be able to "describe the production, properties, and role of surfactant". The topic has come up just once in the written paper, in Question 6 from the second paper of 2012 which asked about the structure of surfactant as well as its effects on surface tension and lung mechanics. The college comment to this SAQ is remarkably detailed, and was very useful in the process of structuring this chapter.
Surface tension and the Law of Laplace:
- Surface tension is the force of attraction between liquid molecules at the liquid-gas interface, expressed in Newtons per meter, which tends to minimise surface area.
- The surface tension of the alveolar fluid, in its tendency to minimise surface area, is a force promoting the collapse of the alveolus.
- The relationhsip of this force to sphere size is described by the Law of Laplace.
- Law of Laplace (P = 2γ/r) states that the pressure difference between the inside and the outside of an elastic sphere ("Laplace pressure") is inversely proportional to the radius.
Consequences of Laplace's law for alveoli
- Smaller partially deflated alveoli will have lower compliance and higher Laplace pressure at any given surface tension
- Increased Laplace pressure upon small alveoli promotes their collapse, as they empty into neighbouring larger alveoli.
- Alveolar surface tension adds to the pulmonary capillary hydrostatic gradient (i.e. it promotes the ultrafiltration of oedema fluid)
- Composed of phospholipid (lecithin) 85%, protein 10%, neutral lipid 5%.
- Secreted by Type 2 alveolar cells, and recycled by them (through endocytosis)
- Half life of 5-10 hours
- Production is stimulated by catecholamines and corticosteroids, and inhibited by surfactant proteins (negative feedback)
Effects of surfactant
- Alveolar surface tension decreases virtually to zero, particularly when alveoli deflate and phospholipid particles are brought closer together
- When the alveoli are fully inflated, surfactant phospholipid molecules are farther apart, which decreases compliance on lung deflation, i.e. it produces hysteresis
- Increased lung compliance results from decreased surface tension
- Decreased surface tension results in a decreased capillary-alveolar hydrostatic pressure gradient, decreasing ultrafiltration of fluid
For surface tension and the law of Laplace, the most illuminating article is probably Prange (2003). Alveolar surfactant seems to be exceptionally popular, and there are several good reviews out there, but many are weakened by excessive detail; the best balance of brevity and thoroughness seems to be Goerke (1998)
Surface tension does not appear to have a formal definition, but this exerpt from the Oxford dictionary seems suitably definition-like:
"the tension of the surface film of a liquid caused by the attraction of the particles in the surface layer by the bulk of the liquid, which tends to minimize surface area."
This is a property of liquids, or specifically of liquid-gas interfaces. The molecules of liquids tend to stick together by strong intermolecular attractive forces (eg. the hydrogen bonds in water), and so the surface of a liquid naturally tends to collect the liquid into a roundish blob (or a sphere, where gravity is not an issue). At least when we are talking about liquids which have these strong intermolecular attractive forces (eg water, the surface tension of which is around 72 mN/m at 25°C). With increasing temperature, surface tension decreases; with increasing intermolecular forces it increases. A good example of extreme surface tension is liquid mercury, which has a surface tension of 487 mN/m. On the other hand, liquid helium is the all-time champion of low surface tension (0.37 mN/m).
The college examiners, in their comment to Question 6 from the second paper of 2012 make reference to something called "La Place's law", likely a reference to Laplace's law (after Pierre-Simon, marquis de Laplace). Its a very famous relationship, and in case one is ever in need of a dozen examples of where it becomes useful in medicine, one may be referred to the excellent article by Jeffrey Basford (2002). For a version which fits an alveolocentric model of the universe, the Young-Laplace-Gauss equation can be represented as:
What is the significance of this? Well, the law itself is fairly straightforward. It basically says that the pressure inside an elastic sphere is inversely proportional to the radius, provided the surface tension remains stable. Obedient to this relationship, at any given surface tension value smaller spheres with smaller radii will have higher transmural pressure, i.e. they want to collapse more than larger spheres. The implications of this law for alveoli are:
That all sounds very scientific, but how well does it represent the goings-on at the alveolar coalface? Probably to some minimal degree, seems to be the answer. Physiology textbooks have been pulling the wool over our eyes, according to Henry Prange (2003). Important points to note regarding the misapplication and limitation of Lapace's law would be:
So, it is probably not 100% applicable to the reality of human lung mechanics. It is an example of medicine misappropriating the precise and streamlined reputations of physics and engineering, trying to press some crisp mathematical edges into the gooey mess of human biology. To borrow Prange's words,
"We biologists often seem driven to seek the elegant and sophisticated mechanisms of physics in the far more complex structures of plants and animals. We are prone to fall into the trap of injecting physics into our work wherever we can, whether or not its use is justified or correct."
When discussing the effect of water surface tension on lung compliance, a famous diagram is often pulled out which demonstrates what would happen of that air-liquid interface was not there. It is a compliance curve of a cat lung (Cat 27's lung, to be precise) which was filled with saline.
This specific version of this diagram comes from T.E. Morgan (1971), but its origins are much older. These data were first published in 1929 by Kurt von Neergaard. At a basic level, this demonstrates that the surface tension of the alveoli makes the lung much more difficult to inflate, i.e. it is one of the most important determinants of lung compliance. With surface tension abolished (no surface, no tension!) the lung inflates apparently effortlessly, and notably also loses the poorly compliant early part of the compliance curve. We are all grateful to Dr Hopkinson, one of the readers, who has submitted this video of a PV look from a surfactant-lacking neonate, as it illustrates the same concept:
The surface tension of water is about 70 mN/m at body temperature, whereas the surface tension of the alveolar surface fluid is obviously quite different. Clements (1957) used a Wilhelmy balance to test the surface tension of mushed lung extract ("mince of whole lungs in normal saline, filtered through loosely-packed cotton") and determined that its surface tension varied from 46 to 10 mN/m, with a substantial hysteresis. This was later confirmed by Schurch Goerke & Clements in 1976. Lachmann et al (1980) demonstrated what this difference means for lung compliance by comparing rabbit lungs before and after a lavage which removed all the surfactant. Their graphics (below) demonstrate the substantial decrease in compliance (it was essentially halved).
So, what is lung surfactant, and where does it get these miraculous properties, and how does it compare to, say, dishwashing detergent?
It is much better than dishwashing detergent, which generally only decreases the surface tension of water down to about 25-30 mN/m. For those with the need to know absolutely everything about this substance, an excellent monograph by Notter & Wang (1997) would be more than enough to agitate their passions. Its 118-page length and the complexity of its contents notwithstanding, in a crime against good typography practice Reviews in Chemical Engineering for some reason published it in a bold font, making it even more difficult to read. No matter: the most important points will be summarised here.
Generally speaking, at the gas-liquid interface, phospholipids tend to form monolayers which are oriented with the hydrophilic heads buried in the water and the hydrophobic tail chains pointing out into the air. The aim of the game is to pack as much of this stuff at the air-liquid interface as possible; the water molecules' attraction to each other is the main reason for the surface tension, and so if you eliminate all the surface water molecules by filling the surface with phospholipid, theoretically the surface tension should be minimised. That is the theory behind the choice of dipalmitoyl phosphatidylcholine, which really isn't found anywhere else except the lungs. As a surfactant agent, this one is a good choice because its disaturated form can be "packed to a very high density at the air–water interface" (Pérez-Gil et al, 2008). You can't do that with many of the other phospholipids because they have "kinked" unsaturated chains which don't line up neatly. Thus, as the alveoli shrink in expiration and their internal surface area decreases, the DPPC molecules bunch together and form an impenetrable waterless carpet at the interface, essentially a solid (albeit a very thin one). Theoretically, this solidification of surfactant should decrease surface tension to zero (Morley & Bangham, 1981). In other words, lung surfactant might under certain circumstances beat the surface tension record of creepy-as-hell superfluid liquid helium, which tends to sneak out of its beaker and generally behaves like a swarm of bosons.
The old CICM syllabus also asked for production and regulation of surfactant, implying that there may be some scenario where one might experience an unregulated surfactant excess. That is in fact the case if one has alveolar proteinosis. Apart from that example, Whitsett et al (2010) describe a range of conditions where the production of surfactant is altered with profound effects.