Surfactant Function and Composition

Why aren’t drops of water flat? Why can some bugs walk on water? Why do babies with RDS have collapsed alveoli? All three of these questions have one explanation: surface tension.

Definition:

Surface tension is a force that reduces the exposed surface of a liquid to the smallest possible area. Surface tension is created at an air-liquid interface through the attraction of molecules in a liquid to each other. The molecules at the surface do not have other liquid molecules above them. For this reason, the molecules at the surface have an unbalanced attraction from molecules below the surface and next to them, but not from above them.

FIGURE 1. Surface tension results from uneven attraction on surface molecules of a liquid

The net direction of surface tension is parallel to a flat surface and toward the middle of a curved surface.

History:

Making the connection of surface tension to pulmonary mechanics was first done in 1929 by Kurt von Neergaard. He compared fluid-filling and air-filling lungs. As seen in figure 2, it takes considerably more pressure to fill lungs with air than with a liquid, in this case saline. Saline filling eliminates any air-liquid interface so only lung tissue elastic fibers oppose filling pressures. Air filling creates a gas-liquid interface; thus, both surface tension and tissue elastic fibers oppose inflation. As the figure shows, more than 80% of the lung elastic forces at full distension are from surface tension. But, at end expiration, both liquid- and air-filled lungs have the same volume. At end expiration, there is no elastic pressure or surface tension pressure remaining to further deflate the lung, meaning surface tension is zero.

Figure 2. Inflation of an excised lung with gas requires 4x as much distending pressure as inflation with a liquid

Lung Surfactant Composition and Activity:

Surfactants are molecules that have a preference for an interface location. (Interface location means air-water interface.) Amphipathic molecules, like surfactant, have two different regions. One region is polar, hydrophilic (water-liking), and the other region is non-polar, hydrophobic (water-hating).

The majority of lung surfactant amphipathic molecules are phospholipids, the same family of molecules that form all the cell membranes and intracellular membranes. The water-loving head of these molecules is a phosphate group + an alcohol group. The tails are two long-chain fatty acids.

Figure 3. Schematic of amphipathic molecule

These molecules form a film that lines the inside of the lung. This film of surfactant molecules at the air-liquid interface lowers the attractive forces between surface molecules of the liquid. The amount of surface tension lowering generated by a lung surfactant film is dependant on the nature of the concentration of the surfactant on the surface. Therefore, surface tension is reduced the most when a monolayer film of surfactant molecules is squeezed close together in expiration.

The surfactant film is produced when molecules enter the surface, a process called "adsorption." During inspiration, the molecules in the film separate as the alveolar surface expands. During expiration, the molecules in the film get squeezed together as tightly as possible, and in fact, some are "squeezed out" of the film because there is no room for them. However, these "squeezed out" molecules remain "associated" with the film and they re-enter the film during the next inspiration, a process called "respreading."

Of the six cell membrane-type phospholipids, only one type, the phosphatidylcholines, make up 90% of lung surfactant phospholipids, and half of these have fatty acid tails with no double bonds (saturated). These are essential for tight packing during surface contraction in expiration.

Four proteins are associated with surfactant. They are named sequentially, A to D (e.g. surfactant protein A is SP-A).Two of the proteins, SP-A and SP-D, are large and have multiple functions in the lung. The other two, SP-B and SP-C, are small, extremely hydrophobic (lipid-like), and have only surfactant-related functions. Only 1 protein, SP-B, is essential for lung surfactant activity, and babies born with congenital SP-B deficiency die of unrelenting RDS without lung transplants. Mice bred to be deficient in SP-B also die at birth. Mice bred deficient in any one of the other surfactant proteins are healthy.

The action of SP-B is to interact with the phospholipids to get them in the surface (adsorption and respreading) and to "order" the phospholipids on the surface (facilitate the close packing) during expiration.

Function of Lung Surfactant

A) Keeping Alveoli Open in Expiration

It is important that the alveoli remain open during expiration and not collapse. Oxygenation of the blood needs to be continuous, not intermittent as it would be if alveoli collapsed after every breath. Lungs with significant surface tension will collapse in expiration. Lung surfactant keeps alveoli open in expiration by lowering surface tension to ~ 0.

In RDS in premature infants, the reason for the respiratory failure is that most of the lung alveoli are collapsed because of surfactant deficiency.

B) Assuring Even Inflation of Alveoli in Inspiration

When an alveolus inflates during inspiration, the surface tension rises, which stops further inflation, and inhaled air is diverted to less well-aerated alveoli. The rise in surface tension during inspiration prevents over-distention of some alveoli and facilitates even distribution of the inhaled gas among all 300,000,000 alveoli that branch from the airway.