Pulmonary surfactant

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Alveoli are the spherical outcroppings of the respiratory bronchioles. An alveolus, is an anatomical structure that has the form of a hollow cavity. Mainly found in the lung, the pulmonary alveoli are spherical outcroppings of the respiratory bronchioles and are the.png
Alveoli are the spherical outcroppings of the respiratory bronchioles.

Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. [1] The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic 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 surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.

Contents

As a medication, pulmonary surfactant is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. [2]

Function

Alveoli can be compared to gas in water, as the alveoli are wet and surround a central air space. The surface tension 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 (γ) and the expanding force of gas in an alveolus of radius r is expressed by the Young–Laplace equation:

Compliance

Compliance is the ability of lungs and thorax 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 and is due to the air-water surface tension that occurs at the beginning of inflation. However, surfactant decreases the alveolar surface tension, 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, 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. [3]

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. [4]

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. [5]

Composition

Lipids

DPPC

Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid with two 16-carbon saturated chains and a phosphate 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 kinetics is very slow. This happens primarily because the phase transition temperature between gel to liquid crystal of pure DPPC is 41.5 °C, which is higher than the human body's temperature of 37 °C. [7]

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.[ citation needed ]

Proteins

Proteins make up the remaining 10% of the surfactant. Half of this 10% is plasma proteins but the rest is formed by the apolipoproteins, 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.

The SP proteins reduce the critical temperature of DPPC's phase transition to a value lower than 37 °C, [10] which improves its adsorption and interface spreading velocity. [11] [12] 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. [13] 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 [12] This also reduces the interface compressibility. [14]

Artificial surfactants

Survanta, surrounded by devices for its application. Pulmonary surfactant.JPG
Survanta, surrounded by devices for its application.

There are a number of types of pulmonary surfactants available. Ex-situ measurements of surface tension and interfacial rheology can help to understand the functionality of pulmonary surfactants. [15]

Synthetic pulmonary surfactants

  1. Colfosceril palmitate (Exosurf) - a mixture of DPPC with hexadecanol and tyloxapol added as spreading agents
  2. Pumactant (Artificial Lung Expanding Compound or ALEC) - a mixture of DPPC and PG
  3. 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.
  4. Venticute - DPPC, PG, palmitic acid and recombinant SP-C
  5. Lucinactant - DPPC, POPG, and palmitic acid.

Animal derived surfactants

  1. Beractant
    1. (Alveofact) - extracted from cow lung lavage fluid
    2. (Survanta) - extracted from minced cow lung with additional DPPC, palmitic acid, and tripalmitin
    3. (Beraksurf) -extracted from minced calf lung with additional DPPC, palmitic acid, and tripalmitin
  2. Calfactant (Infasurf) - extracted from calf lung lavage fluid
  3. Poractant alfa (Curosurf) - extracted from material derived from minced pig lung
  4. 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. [ citation needed ]

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. [11] [13] [14]

Surface tension values
ConditionTension (mN/m)
Water at 25 °C70
Pulmonary surfactant in equilibrium at 36 °C25
Healthy lung at 100% of TLC 30
Healthy lung between 40 and 60% of TLC 1~6
Healthy lung below 40% of TLC <1

Production and degradation

Surfactant production in humans begins in type II cells during the alveolar sac stage of lung development. Lamellar bodies appear in the cytoplasm at about 20 weeks gestation. [16] These lamellar bodies are secreted by exocytosis into the alveolar lining fluid, where the surfactant forms a meshwork of tubular myelin [17] [18] Full term 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. [19]

Club cells also produce a component of lung surfactant. [20]

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 dependent endocytosis. [21] The other 10% is taken up by alveolar macrophages and digested.

Diseases

History

In late 1920s von Neergaard [22] 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). [23] [13]

Related Research Articles

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Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.

<span class="mw-page-title-main">Lung</span> Primary organ of the respiratory system

The lungs are the most important organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of the heart. Their function in the respiratory system is to extract oxygen from the air and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. The pleurae, which are thin, smooth, and moist, serve to reduce friction between the lungs and chest wall during breathing, allowing for easy and effortless movements of the lungs.

<span class="mw-page-title-main">Respiratory system</span> Biological system in animals and plants for gas exchange

The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals, the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles, these are called alveoli, and in birds, they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds, the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.

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<span class="mw-page-title-main">Dipalmitoylphosphatidylcholine</span> Chemical compound

Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group.

<span class="mw-page-title-main">Lamellar bodies</span> Secretory organelles

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<span class="mw-page-title-main">Surfactant protein B</span> Protein-coding gene in the species Homo sapiens

Surfactant protein B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. It rearranges lipid molecules in the fluid lining the lung so that tiny air sacs in the lung, called alveoli, can more easily inflate.

<span class="mw-page-title-main">Phosphatidylglycerol</span> Lipid

Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant and in the plasma membrane where it directly activates lipid-gated ion channels.

<span class="mw-page-title-main">Surfactant protein A1</span> Protein-coding gene in the species Homo sapiens

Surfactant protein A1(SP-A1), also known as Pulmonary surfactant-associated protein A1(PSP-A) is a protein that in humans is encoded by the SFTPA1 gene.

<span class="mw-page-title-main">Surfactant protein A2</span> Protein-coding gene in the species Homo sapiens

Surfactant protein A2(SP-A2), also known as Pulmonary surfactant-associated protein A2(PSP-A2) is a protein that in humans is encoded by the SFTPA2 gene.

<span class="mw-page-title-main">Lecithin–sphingomyelin ratio</span> Test of fetal amniotic fluid to assess for lung immaturity

The lecithin–sphingomyelin ratio is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs. This is especially important for premature babies trying to expand their lungs after birth. Surfactant is a mixture of lipids, proteins, and glycoproteins, lecithin and sphingomyelin being two of them. Lecithin makes the surfactant mixture more effective.

<span class="mw-page-title-main">Diffuse alveolar damage</span> Medical condition

Diffuse alveolar damage (DAD) is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome (ARDS). It is important to note that DAD can be seen in situations other than ARDS (such as acute interstitial pneumonia) and that ARDS can occur without DAD.

Poractant alfa is a pulmonary surfactant sold under the brand name Curosurf by Chiesi Farmaceutici. Poractant alfa is an extract of natural porcine lung surfactant. As with other surfactants, marked improvement on oxygenation may occur within minutes of the administration of poractant alfa. The new generic form of surfactant is Varasurf developed in PersisGen Co. and commercialized by ArnaGen Pharmad. It has fully comparable quality profile with Curosurf.

Surfactant metabolism dysfunction is a condition where pulmonary surfactant is insufficient for adequate respiration. Surface tension at the liquid-air interphase in the alveoli makes the air sacs prone to collapsing post expiration. This is due to the fact that water molecules in the liquid-air surface of alveoli are more attracted to one another than they are to molecules in the air. For sphere-like structures like alveoli, water molecules line the inner walls of the air sacs and stick tightly together through hydrogen bonds. These intermolecular forces put great restraint on the inner walls of the air sac, tighten the surface all together, and unyielding to stretch for inhalation. Thus, without something to alleviate this surface tension, alveoli can collapse and cannot be filled up again. Surfactant is essential mixture that is released into the air-facing surface of inner walls of air sacs to lessen the strength of surface tension. This mixture inserts itself among water molecules and breaks up hydrogen bonds that hold the tension. Multiple lung diseases, like ISD or RDS, in newborns and late-onsets cases have been linked to dysfunction of surfactant metabolism.

Beractant, also known by the trade name of Survanta, is a modified bovine pulmonary surfactant containing bovine lung extract, to which synthetic DPPC, tripalmitin and palmitic acid are added. The composition provides 25 mg/mL phospholipids, 0.5 to 1.75 mg/mL triglycerides, 1.4 to 3.5 mg/mL free fatty acids, and <1.0 mg/mL total surfactant proteins. As an intratracheal suspension, it can be used for the prevention and treatment of neonatal respiratory distress syndrome. Survanta is manufactured by Abbvie.

<span class="mw-page-title-main">Pulmonary surfactant (medication)</span>

Pulmonary surfactant is used as a medication to treat and prevent respiratory distress syndrome in newborn babies.

Development of the respiratory system begins early in the fetus. It is a complex process that includes many structures, most of which arise from the endoderm. Towards the end of development, the fetus can be observed making breathing movements. Until birth, however, the mother provides all of the oxygen to the fetus as well as removes all of the fetal carbon dioxide via the placenta.

References

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  2. ↑ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
  3. ↑ "Alveoli and the Breathing Process". Archived from the original on 2015-05-18. Retrieved 2013-10-30.[ unreliable medical source? ]
  4. ↑ West, John B. (1994). Respiratory physiology-- the essentials . Baltimore: Williams & Wilkins. ISBN   0-683-08937-4.[ page needed ]
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  7. ↑ Albon N (1978). "Nature of the gel to liquid crystal transition of synthetic phosphatidylcholines". Proceedings of the National Academy of Sciences of the United States of America. 75 (5): 2258–2260. Bibcode:1978PNAS...75.2258A. doi: 10.1073/pnas.75.5.2258 . PMC   392531 . PMID   276866.
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  13. 1 2 3 Veldhuizen R, Nag K, Orgeig S, Possmayer F (1998). "The role of lipids in pulmonary surfactant". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1408 (2–3): 90–108. doi: 10.1016/S0925-4439(98)00061-1 . PMID   9813256.
  14. 1 2 Schürch S, Bachofen H, Possmayer F (2001). "Surface activity in situ, in vivo, and in the captive bubble surfactometer". Comparative Biochemistry and Physiology A. 129 (1): 195–207. doi:10.1016/S1095-6433(01)00316-6. PMID   11369544.
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