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Pulmonary surfactant is a surface-active complex of
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s and
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s formed by type II alveolar cells. The proteins and lipids that make up the
surfactant Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word ''surfactant'' is a Blend word, blend of "surface-active agent", coined in ...
have both
hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...
and
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
regions. By adsorbing to the air-water interface of alveoli, with hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of the surfactant,
dipalmitoylphosphatidylcholine Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breath ...
(DPPC), reduces
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
. As a medication,
pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by Type II cells, type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorption, adso ...
is on the
WHO Model List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
, the most important medications needed in a basic
health system A health system, health care system or healthcare system is an organization of people, institutions, and resources that delivers health care services to meet the health needs of target populations. There is a wide variety of health systems aroun ...
.


Function

* To increase pulmonary compliance. * To prevent
atelectasis Atelectasis is the partial collapse or closure of a lung resulting in reduced or absence in gas exchange. It is usually unilateral, affecting part or all of one lung. It is a condition where the Pulmonary alveolus, alveoli are deflated down to l ...
(collapse of the alveoli or atriums) at the end of expiration. * To facilitate recruitment of collapsed airways. Alveoli can be compared to gas in water, as the alveoli are wet and surround a central air space. The
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
acts at the air-water interface and tends to make the bubble smaller (by decreasing the surface area of the interface). The gas pressure (''P'') needed to keep an equilibrium between the collapsing force of
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
(''γ'') and the expanding force of gas in an alveolus of radius ''r'' is expressed by the
Young–Laplace equation In physics, the Young–Laplace equation () is an equation that describes the capillary pressure difference sustained across the interface between two static fluids, such as water and air, due to the phenomenon of surface tension or wall tensi ...
: : P = \frac


Compliance

Compliance is the ability of
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s and
thorax The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...
to expand. Lung compliance is defined as the volume change per unit of pressure change across the lung. Measurements of lung volume obtained during the controlled inflation/deflation of a normal lung show that the volumes obtained during deflation exceed those during inflation, at a given pressure. This difference in inflation and deflation volumes at a given pressure is called
hysteresis Hysteresis is the dependence of the state of a system on its history. For example, a magnet may have more than one possible magnetic moment in a given magnetic field, depending on how the field changed in the past. Plots of a single component of ...
and is due to the air-water surface tension that occurs at the beginning of inflation. However, surfactant decreases the alveolar
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
, as seen in cases of premature infants with infant respiratory distress syndrome. The normal surface tension for water is 70 dyn/cm (70 mN/m) and in the lungs, it is 25 dyn/cm (25 mN/m); however, at the end of the expiration, compressed surfactant phospholipid molecules decrease the surface tension to very low, near-zero levels. Pulmonary surfactant thus greatly reduces
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
, increasing compliance allowing the lung to inflate much more easily, thereby reducing the work of breathing. It reduces the pressure difference needed to allow the lung to inflate. The lung's compliance, and ventilation decrease when lung tissue becomes diseased and fibrotic.


Alveolar size regulation

As the alveoli increase in size, the surfactant becomes more spread out over the surface of the liquid. This increases surface tension effectively slowing the rate of expansion of the alveoli. This also helps all alveoli in the lungs expand at the same rate, as one that expands more quickly will experience a large rise in surface tension slowing its rate of expansion. It also means the rate of shrinking is more regular as if one reduces in size more quickly the surface tension will reduce more, so other alveoli can contract more easily than it can. Surfactant reduces surface tension more readily when the alveoli are smaller because the surfactant is more concentrated.


Prevention of fluid accumulation and maintenance of dryness of airways

Surface tension draws fluid from capillaries to the alveolar spaces. Surfactant reduces fluid accumulation and keeps the airways dry by reducing surface tension.


Innate immunity

Surfactant immune function is primarily attributed to two proteins: SP-A and SP-D. These proteins can bind to sugars on the surface of pathogens and thereby opsonize them for uptake by phagocytes. It also regulates inflammatory responses and interacts with the adaptive immune response. Surfactant degradation or inactivation may contribute to enhanced susceptibility to lung inflammation and infection.


Composition

* ~40%
dipalmitoylphosphatidylcholine Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breath ...
(DPPC); * ~40% other
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s (PC); * ~10% surfactant
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
( SP-A, SP-B, SP-C and SP-D); * ~10% neutral
lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...
(
Cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
); * Traces of other substances.


Lipids


DPPC

Dipalmitoylphosphatidylcholine Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breath ...
(DPPC) is a
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
with two 16-carbon saturated chains and a
phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
group with quaternary amine group attached. The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has a higher compaction capacity than the other phospholipids, because the apolar tail is less bent. Nevertheless, without the other substances of the pulmonary surfactant mixture, the DPPC's
adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...
kinetics is very slow. This happens primarily because the phase transition temperature between gel to
liquid crystal Liquid crystal (LC) is a state of matter whose properties are between those of conventional liquids and those of solid crystals. For example, a liquid crystal can flow like a liquid, but its molecules may be oriented in a common direction as i ...
of pure DPPC is 41.5 °C, which is higher than the human body's temperature of 37 °C.


Other phospholipids

Phosphatidylcholine molecules form ~85% of the lipid in surfactant and have saturated acyl chains. Phosphatidylglycerol (PG) forms about 11% of the lipids in the surfactant, it has unsaturated fatty acid chains that fluidize the lipid monolayer at the interface. Neutral lipids and cholesterol are also present. The components for these lipids diffuse from the blood into type II alveolar cells where they are assembled and packaged for secretion into secretory organelles called
lamellar bodies In cell biology, lamellar bodies (otherwise known as lamellar granules, membrane-coating granules (MCGs), keratinosomes or Odland bodies) are secretory organelles found in Alveolar cell, type II alveolar cells in the lungs, and in keratinocytes i ...
.


Proteins

Proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
make up the remaining 10% of the surfactant. Half of this 10% is plasma proteins but the rest is formed by the
apolipoprotein Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoprotei ...
s, surfactant proteins SP-A, SP-B, SP-C, and SP-D. The apolipoproteins are produced by the secretory pathway in type II cells. They undergo much post-translational modification, ending up in the lamellar bodies. These are concentric rings of lipid and protein, about 1 μm in diameter. * SP-A and SP-D are collectins. They confer innate immunity as they have carbohydrate recognition domains that allow them to coat bacteria and viruses promoting phagocytosis by macrophages. SP-A is also thought to be involved in a negative feedback mechanism to control the production of surfactant. * SP-B and SP-C are hydrophobic membrane proteins that increase the rate that surfactant spreads over the surface. SP-B and SP-C are required for the proper biophysical function of the lung. Humans and animals born with a congenital absence of the saposin family SP-B experience intractable respiratory failure whereas those born lacking SP-C tend to develop progressive interstitial pneumonitis. The SP proteins reduce the critical temperature of DPPC's
phase transition In physics, chemistry, and other related fields like biology, a phase transition (or phase change) is the physical process of transition between one state of a medium and another. Commonly the term is used to refer to changes among the basic Sta ...
to a value lower than 37 °C, which improves its adsorption and interface spreading velocity. The compression of the interface causes a phase change of the surfactant molecules to liquid-gel or even gel-solid. The fast adsorption velocity is necessary to maintain the integrity of the gas exchange region of the lungs. Each SP protein has distinct functions, which act synergistically to keep an interface rich in DPPC during lung's expansion and contraction. Changes in the surfactant mixture composition alter the pressure and temperature conditions for phase changes and the phospholipids' crystal shape as well. Only the liquid phase can freely spread on the surface to form a monolayer. Nevertheless, it has been observed that if a lung region is abruptly expanded the floating crystals crack like " icebergs". Then the SP proteins selectively attract more DPPC to the interface than other phospholipids or cholesterol, whose surfactant properties are worse than DPPC's. The SP also fastens the DPPC on the interface to prevent the DPPC from being squeezed out when the surface area decreases This also reduces the interface compressibility.


Artificial surfactants

There are a number of types of pulmonary surfactants available. Ex-situ measurements of
surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...
and interfacial rheology can help to understand the functionality of pulmonary surfactants. Synthetic pulmonary surfactants # Colfosceril palmitate (Exosurf) - a mixture of DPPC with hexadecanol and tyloxapol added as spreading agents # Pumactant (Artificial Lung Expanding Compound or ALEC) - a mixture of DPPC and PG # KL-4 - composed of DPPC, palmitoyl-oleoyl phosphatidylglycerol, and palmitic acid, combined with a 21 amino acid synthetic peptide that mimics the structural characteristics of SP-B. # Venticute - DPPC, PG, palmitic acid and recombinant SP-C # Lucinactant - DPPC, POPG, and
palmitic acid Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The ...
. Animal derived surfactants # Beractant ## (Alveofact) - extracted from cow lung lavage fluid ## (Survanta) - extracted from minced cow lung with additional DPPC, palmitic acid, and tripalmitin ##(Beraksurf) -extracted from minced calf lung with additional DPPC, palmitic acid, and tripalmitin # Calfactant (Infasurf) - extracted from calf lung lavage fluid # Poractant alfa (Curosurf) - extracted from material derived from minced pig lung # Ovinactant (Varasurf) - extracted from material derived from minced sheep lung


Surface tension magnitude inside the lung

Even though the surface tension can be greatly reduced by pulmonary surfactant, this effect will depend on the surfactant's concentration on the interface. The interface concentration has a saturation limit, which depends on temperature and mixture composition. Because during ventilation there is a variation of the lung surface area, the surfactant's interface concentration is not usually at the level of saturation. The surface increases during inspiration, which consequently opens space for new surfactant molecules to be recruited to the interface. Meanwhile, during expiration the surface area decreases at a rate which is always in excess of the rate at which the surfactant molecules are driven from the interface into the water film. Thus, the surfactant density at the air water interface remains high and is relatively preserved throughout expiration, decreasing the surface tension even further. This also explains why the compliance is greater during expiration than during inspiration. SP molecules contribute to increasing the surfactant interface adsorption kinetics, when the concentration is below the saturation level. They also make weak bonds with the surfactant molecules at the interface and hold them longer there when the interface is compressed. Therefore, during ventilation, surface tension is usually lower 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 tissue damage at high volume levels.


Production and degradation

Surfactant production in humans begins in type II cells during the alveolar sac stage of lung development.
Lamellar bodies In cell biology, lamellar bodies (otherwise known as lamellar granules, membrane-coating granules (MCGs), keratinosomes or Odland bodies) are secretory organelles found in Alveolar cell, type II alveolar cells in the lungs, and in keratinocytes i ...
appear in the cytoplasm at about 20 weeks gestation. These lamellar bodies are secreted by
exocytosis Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
into the alveolar lining fluid, where the surfactant forms a meshwork of tubular myelin
Full term Pregnancy is the time during which one or more offspring gestates inside a woman's uterus. A multiple pregnancy involves more than one offspring, such as with twins. Conception usually occurs following vaginal intercourse, but can also ...
infants are estimated to have an alveolar storage pool of approximately 100 mg/kg of surfactant, while preterm infants have an estimated 4–5 mg/kg at birth. Club cells also produce a component of lung surfactant. Alveolar surfactant has a half-life of 5 to 10 hours once secreted. It can be both broken down by macrophages and/or reabsorbed into the lamellar structures of type II pneumocytes. Up to 90% of surfactant DPPC (dipalmitoylphosphatidylcholine) is recycled from the alveolar space back into the type II pneumocyte. This process is believed to occur through SP-A stimulating receptor-mediated,
clathrin Clathrin is a protein that plays a role in the formation of coated vesicles. Clathrin was first isolated by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskel ...
dependent
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...
. The other 10% is taken up by alveolar macrophages and digested.


Diseases

* Infant respiratory distress syndrome (IRDS) is caused by lack of surfactant, commonly seen in premature babies born before 28–32 weeks of gestation. * Congenital surfactant deficiency * Pulmonary alveolar proteinosis * Surfactant metabolism dysfunction


History

In late 1920s von Neergaard identified the function of the pulmonary surfactant in increasing the compliance of the lungs by reducing surface tension. However the significance of his discovery was not understood by the scientific and medical community at that time. He also realized the importance of having low surface tension in lungs of newborn infants. Later, in the middle of the 1950s, Pattle and Clements rediscovered the importance of surfactant and low surface tension in the lungs. At the end of that decade it was discovered that the lack of surfactant caused infant respiratory distress syndrome (IRDS).


References


External links

{{DEFAULTSORT:Pulmonary Surfactant Respiratory physiology Integral membrane proteins Surfactants Pulmonary function testing Lipopeptides