Surfactants: Function, History, Composition, Types, Magnitude, Production, Degradation and Medical Uses

It is a fluid secreted by the cells of the alveoli (the small air sacs in the lungs) that serves to reduce the surface tension of the pulmonary fluids.

The surfactant contributes to the elastic properties of the lung tissue, preventing the alveoli from collapsing.

Pulmonary surfactant is a surface active lipoprotein complex (phospholipoprotein) formed by type II alveolar cells. The proteins and lipids that make up the surfactant have hydrophilic and hydrophobic regions.

Adsorbing the air-water interface of the alveoli, with hydrophilic groups in the water and the hydrophobic tails facing the air, the main lipid component of the surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces the surface tension.

As a medicine, lung surfactant is on the WHO Model List of Essential Drugs, the most important drugs needed in a basic health system.


  • To increase lung compliance.
  • To prevent atelectasis (collapse of the lung) at the end of expiration.
  • To facilitate the recruitment of collapsed airways.

The alveoli can be compared to the gas in the water, since the alveoli are moist and surround a central air space.


Compliance is the ability of the lungs and the chest to expand. The pulmonary compliance is defined as the volume change per unit pressure change through the lung.

This difference in the volumes of inflation and deflation at a given pressure is called hysteresis and is due to the air-water surface tension that occurs at the beginning of inflation.

However, the surfactant decreases the alveolar surface tension, as observed in the cases of premature infants suffering from infant respiratory distress syndrome.

The normal surface tension for water is 70dyn / cm (70mN / m) and in the lungs it is 25dyn / cm (25mN / m); however, at the end of expiration, the compressed surfactant phospholipid molecules decrease the surface tension to very low levels, close to zero.

Reduces the pressure difference needed to allow the lung to inflate. Compliance with the lung decreases and ventilation decreases when the lung tissue becomes diseased and fibrotic.

Alveolar size regulation

As the alveoli increase in size, the surfactant extends further along the surface of the liquid. This increases the surface tension by effectively reducing the expansion speed of the alveoli.

It also means that the speed of contraction is more regular, because if you reduce the size more quickly, the surface tension will be reduced more, so that other alveoli can contract more easily than they can.

Prevent the accumulation of fluids and keep the airways dry

The surface tension forces also extract fluid from the capillaries to the alveolar spaces. The surfactant reduces fluid accumulation and keeps the airway dry by reducing these forces.

Innate immunity

The immune function of the surfactant is attributed mainly to two proteins: SP-A and SP-D. These proteins can bind to sugars on the surface of pathogens and, therefore, opsonize them for their uptake by phagocytes.

The degradation or inactivation of surfactant can contribute to an increased susceptibility to inflammation and lung infection.


  • ~ 40% de dipalmitoilfosfatidilcolina (DPPC).
  • ~ 40% of other phospholipids (PC).
  • ~ 10% surfactant proteins (SP-A, SP-B, SP-C and SP-D).
  • ~ 10% neutral lipids (cholesterol).
  • Traces of other substances.



Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid with two saturated chains of 16 carbons and a phosphate group with a bound quaternary amine group.

dipalmitoylphosphatidylcholine is the strongest surfactant molecule in the pulmonary surfactant mixture.

This occurs mainly because the phase transition temperature between the gel and the liquid crystal of pure DPPC is 41.5 ° C, which is higher than the human body temperature of 37 ° C.

Other phospholipids

Phosphatidylcholine molecules form ~85% of the lipids in the surfactant and have saturated acyl chains. Phosphatidylglycerol (PG) has chains of unsaturated fatty acids that fluidize the lipid monolayer at the interface.

Neutral lipids and cholesterol are also present. The components of these lipids diffuse from the blood to type II alveolar cells where they are assembled and packaged for secretion into secretory organelles called lamellar bodies.


The proteins constitute the remaining 10% of the surfactant. Half of this 10% are plasma proteins, but the rest is formed by the apolipoproteins, surfactant proteins SP-A, SP-B, SP-C and SP-D.

Apolipoproteins are produced by the secretory pathway in type II cells. They undergo much post-translational modification, ending in the lamellar bodies.

The SP-A and SP-D proteins confer innate immunity since they have carbohydrate recognition domains that allow them to coat bacteria and viruses promoting phagocytosis by macrophages .

The SP proteins reduce the critical temperature of the dipalmitoylphosphatidylcholine phase transition to a value below 37 ° C, which improves its adsorption and the propagation speed of the interface.

Each SP protein has different functions, which act synergistically to maintain an interface rich in dipalmitoylphosphatidylcholine during the expansion and contraction of the lung.

Then SP proteins selectively attract more dipalmitoylphosphatidylcholine to the interface than other phospholipids or cholesterol, whose surfactant properties are worse than dipalmitoylphosphatidylcholines.

SP also binds dipalmitoylphosphatidylcholine at the interface to prevent dipalmitoylphosphatidylcholine from being squeezed when the surface area decreases.

Magnitude of surface tension within the lung

Although the surface tension can be greatly reduced with the pulmonary surfactant, this effect will depend on the concentration of the surfactant at the interface.

The concentration of the interface has a saturation limit, which depends on the temperature and composition of the mixture.

Because during ventilation there is a variation of the surface area of ​​the lung, the concentration of the interface of the surfactant is usually not at the level of saturation.

The surface increases during inspiration, which opens space for new surfactant molecules to be recruited at the interface.

Meanwhile, upon expiration of the surface area decreases, the surfactant layer is compressed, bringing the surfactant molecules closer together and further decreasing the surface tension.

SP molecules establish weak bonds with the surfactant molecules at the interface and keep them there for a longer time when the interface is compressed. Therefore, during ventilation, the surface tension is usually less than at equilibrium.

Therefore, the surface tension varies according to the volume of air in the lungs, which protects them from atelectasis at low volumes and from tissue damage at high volume levels.

Production and degradation

The production of surfactant in humans begins in type II cells during the alveolar sac stage of lung development. The lamellar bodies appear in the cytoplasm around 20 weeks of gestation.

These lamellar bodies are secreted by exocytosis in the layer of surface water that lines the alveolar space, where the surfactant forms a network of tubular myelin.

It is estimated that term infants have an alveolar storage group of approximately 100mg / kg of surfactant, while premature infants have an estimated 4-5 mg / kg at birth.

Club cells, also known as bronchiolar exocrine cells, also produce a component of pulmonary surfactant.

The alveolar surfactant has a half-life of 5 to 10 hours once secreted. Up to 90% of the surfactant DPPC (dipalmitoyl phosphatidylcholine) is recycled from the alveolar space to the pneumocyte type II.

It is believed that this process occurs through the clathrin-dependent endocytosis mediated by the stimulating receptor SP-A. The other 10% is absorbed by the alveolar macrophages and digested.


In the late 1920s, von Neergaard identified the function of the pulmonary surfactant to increase compliance of the lungs by reducing surface tension.

He also realized the importance of having low surface tension in the lungs of newborn babies.

Pulmonary surfactant (medication)

Pulmonary surfactant is used as a medication to treat and prevent respiratory distress syndrome in newborn babies. Prevention is usually done in babies born with less than 32 weeks of gestational age.

It is administered by the endotracheal tube. The start of the effects is fast. Several doses may be needed.

Side effects can include slow heartbeat and low oxygen levels. Its use is also related to intracranial bleeding. Pulmonary surfactant can be isolated from the lungs of cows or pigs or it can be artificially made.

Pulmonary surfactant was discovered in the 1950s and a manufactured version was approved for medical use in the United States in 1990.

It is on the list of essential medicines of the World Health Organization, the most effective and safe medicines that are needed in a health system. In the United Kingdom costs the NHS 281.64 to 547.40 pounds per dose.

Medical uses

Pulmonary surfactant is used to treat and prevent respiratory distress syndrome in newborn babies. Prevention is usually done in babies born with less than 32 weeks of gestational age. Tentative evidence supports use in drowning.


There are several types of lung surfactants available. Like their natural counterparts, preparations of pulmonary surfactants consist of phospholipids (mainly dipalmitoylphosphatidylcholine) combined with blowing agents such as SP-B and SP-C.

Synthetic pulmonary surfactants:

  • Colfosceryl palmitate (Exosurf): a mixture of dipalmitoylphosphatidylcholine with hexadecanol and tyloxapol added as extension agents.
  • Pumactant (Artificial Lung Expansive Compound): a mixture of dipalmitoylphosphatidylcholine and PG.
  • KL-4: composed of DPPC, palmitoyl-oleoyl phosphatidylglycerol and palmitic acid, combined with a synthetic peptide of 21 amino acids (sinapultide) that mimics the structural characteristics of SP-B.
  • Venticute: dipalmitoylphosphatidylcholine, PG, palmitic acid and recombinant SP-C.

Surfactants derived from animals:

  • Beractant
  • Alveofact: extracted from the pulmonary lavage fluid of the cow, manufactured by Boehringer ingelheim.
  • Survanta: extracted from the chopped cow’s lung with additional dipalmitoylphosphatidylcholine, palmitic acid and tripalmitin, manufactured by Abbvie.
  • Beraksurf: extracted from the lung of the minced cow with additional dipalmitoylphosphatidylcholine, palmitic acid and manufacture of tripalmitin by Tekzima.
  • Calfactant (Infasurf): extracted from the lung wash fluid of the calf.
  • Poractant alfa (Curosurf) : extracted from the material derived from the chopped pig lung.

Researcher John Clements identified surfactants and their role in the 1950s. Mary Ellen Avery shortly afterwards demonstrated that the lungs of premature babies could not produce surfactants.

Exosurf, Curosurf, Infasurf and Survanta were the initial surfactants approved by the Food and Drug Administration for use in the USA. UU In 2012, the US Food and Drug Administration UU Approved an additional synthetic surfactant, lucinactant (Surfaxin).


The deficiency of pulmonary surfactant is the main cause of respiratory distress syndrome in premature babies. Four proteins associated with surfactant, surfactant proteins A, B, C and D have been described, and two have been associated with diffuse pulmonary parenchymal diseases.

Surfactant protein C (SP-C) is a highly hydrophobic protein that improves the properties of decreasing the surface tension of the pulmonary surfactant.

Familial cases of neonatal respiratory distress have been associated with surfactant protein B deficiency, but respiratory distress in newborns is not considered a form of diffuse parenchymal lung disease / interstitial lung disease.

Genetic variants of SP-A have been associated with an increased risk of idiopathic pulmonary fibrosis.

Congenital deficiency of surfactant

The dysfunction of the surfactant metabolism is a condition where the pulmonary surfactant is insufficient for adequate respiration.

Most disease-causing mutations in SFTPB result in a complete lack of mature SP-B protein 265120. Lung disease is inherited in an autosomal recessive manner, requiring mutations in both alleles.

The surfactant produced by babies with SP-B deficiency is abnormal in its composition and does not function normally when the surface tension decreases.

Family cases of SP-C 610913 dysfunction are inherited in an autosomal dominant pattern, although the onset and severity of lung disease are highly variable, even within the same family.

Mutations in ABCA3 appear to be the most common cause of genetic surfactant dysfunction in humans. Mutations result in a loss or reduced function of the ABCA3 protein, and are inherited in an autosomal recessive fashion 610921.

Proteinosis alveolar pulmonar

Pulmonary alveolar proteinosis (PAP) is a group of rare lung disorders characterized by the abnormal accumulation of surfactant-derived lipoprotein compounds within the alveoli of the lung.

The accumulated substances interfere with the normal exchange of gases and the expansion of the lungs, which ultimately causes difficulty in breathing and a predisposition to develop lung infections.

The causes of pulmonary alveolar proteinosis can be grouped into primary and secondary causes, although the most common etiology is a primary autoimmune condition.