Pulmonary surfactant - AbsoluteAstronomy.com

Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein) formed by type II alveolar cells

Pulmonary alveolus

An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...

. The proteins and lipids that surfactant

Surfactant

Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...

comprises have both a hydrophilic region and a hydrophobic region. By adsorbing

Adsorption

Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface. This process creates a film of the adsorbate on the surface of the adsorbent. It differs from absorption, in which a fluid permeates or is dissolved by a liquid or solid...

to the air-water interface

Interface (chemistry)

An interface is a surface forming a common boundary among two different phases, such as an insoluble solid and a liquid, two immiscible liquids or a liquid and an insoluble gas. The importance of the interface depends on which type of system is being treated: the bigger the quotient area/volume,...

of alveoli with the hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine

Dipalmitoylphosphatidylcholine

Dipalmitoylphosphatidylcholine is a phospholipid consisting of two palmitic acids and is the major constituent of pulmonary surfactant. It is also the only surface active component of lung surfactant capable of lowering surface tension to near zero levels. DpPC is synthesized mainly through...

(DPPC), reduces surface tension

Surface tension

Surface tension is a property of the surface of a liquid that allows it to resist an external force. It is revealed, for example, in floating of some objects on the surface of water, even though they are denser than water, and in the ability of some insects to run on the water surface...

Function

To increase pulmonary compliance
Pulmonary compliance
Pulmonary compliance can refer to either dynamic or static lung compliance. Static lung compliance is the change in volume for any given applied pressure...

.
To prevent atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...

(collapse of the lung) 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

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 equilibrium between the collapsing force of surface tension

Surface tension

(γ) and the expanding force of gas in an alveolus of radius r is expressed by the law of Laplace:

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

Lung

The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

. 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

Hysteresis is the dependence of a system not just on its current environment but also on its past. This dependence arises because the system can be in more than one internal state. To predict its future evolution, either its internal state or its history must be known. If a given input alternately...

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

, as seen in cases of premature infants suffering from infant respiratory distress syndrome

Infant respiratory distress syndrome

Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

. 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

, increasing compliance allowing the lung to inflate much more easily, thereby eliminating the work of breathing. It reduces the pressure difference needed to allow the lung to inflate. The reduction in surface tension also reduces fluid accumulation in the alveolus as the surface tension draws fluid across the alveolar wall.

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.

Keeping airways dry

Surface tension forces also draw fluid from capillaries to the alveolar spaces. Surfactant keeps the airways dry by reducing these forces.

Composition

~40% dipalmitoylphosphatidylcholine
Dipalmitoylphosphatidylcholine
Dipalmitoylphosphatidylcholine is a phospholipid consisting of two palmitic acids and is the major constituent of pulmonary surfactant. It is also the only surface active component of lung surfactant capable of lowering surface tension to near zero levels. DpPC is synthesized mainly through...

(DPPC);
∼40% other phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

s (PC);
~5% surfactant-associated proteins (SP-A, B, C and D);
Cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

(neutral lipids);
Traces of other substances
Chemical substance
In chemistry, a chemical substance is a form of matter that has constant chemical composition and characteristic properties. It cannot be separated into components by physical separation methods, i.e. without breaking chemical bonds. They can be solids, liquids or gases.Chemical substances are...

.

DPPC

This is a phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

with two 16-carbon saturated chains and a phosphate

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

group with quaternary amine group attached. The DPPC is the strongest surfactant molecule in the pulmonary surfactant mixture. It also has 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

kinetics is very slow. This happens primarily because the phase transition temperature

Transition temperature

Transition temperature is the temperature at which a material changes from one crystal state to another. There are seven crystal systems and every crystallized material exists in one of them....

between gel

Gel

A gel is a solid, jelly-like material that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state...

to liquid crystal

Liquid crystal

Liquid crystals are a state of matter that have properties between those of a conventional liquid and those of a solid crystal. For instance, an LC may flow like a liquid, but its molecules may be oriented in a crystal-like way. There are many different types of LC phases, which can be...

of pure DPPC is 41°C, which is higher than the human body's.

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

Lamellar bodies

Lamellar granules are secretory organelles found in type II pneumocytes and keratinocytes. They are oblong structures, appearing about 300-400 nm in width and 100-150 nm in length in transmission electron microscopy images...

Proteins

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

Apolipoprotein

Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....

s SP-A , B , C and D (SP standing for "surfactant-associated protein"). 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
Surfactant protein A
Surfactant protein A is an innate immune system collectin.- During Parturition :The role of Surfactant protein A in childbirth is indicated in studies with mice. Mice which gestate for 19 days typically show signs of SP-A in amniotic fluid at around 16 days. If SP-A is injected into the uterus at...

and SP-D 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 proper biophysical function of the lung. Humans and animals born with a congenital absence of SP-B suffer from 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 to a value lower than 37°C, what 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 synergetically 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

Synthetic pulmonary surfactants

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

Animal derived surfactants

Alveofact - extracted from cow lung lavage fluid
Curosurf - extracted from material derived from minced pig lung
Infasurf - extracted from calf lung lavage fluid
Survanta - extracted from minced cow lung with additional DPPC, palmitic acid and tripalmitin

Exosurf, Curosurf, Infasurf, and Survanta are the surfactants currently FDA approved for use in the U.S.

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 at the expiration the surface area decreases, the layer of surfactant is squeezed, bringing the surfactant molecules closer to each other and further decreasing the surface tension.

SP molecules contribute to increase the surfactant interface adsorption kinetics, when the concentration is below the saturation

Saturation (chemistry)

In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...

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.

Surface tension values
Condition	Tension (mN/m)
Water at 25°C	70
Pulmonary surfactant in equilibrium at 36°C	25
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

Surfactant production in humans begins in Type II cells during the terminal sac stage of lung development. Lamellar bodies appear in the cytoplasm at about 20 weeks gestation. These lamellar bodies are secreted by exocytosis

Exocytosis

Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

into the surface water layer lining the alveolar airspace, where the surfactant forms a meshwork of tubular myelin

Myelin

Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...

. 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. This alveolar surfactant can be both broken down by macrophages and/or reabsorbed into the lamellar structures of type II cells. Up to 90% of surfactant phosphatidylcholine is recycled from the alveolar space in the newborn.

Clara cell

Clara cell

Clara cells are dome-shaped cells with short microvilli found in the small airways of the lungs.Clara cells are found in the ciliated simple epithelium...

s also produce a component of lung surfactant.

Diseases

Infant respiratory distress syndrome
Infant respiratory distress syndrome
Infant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural...

(IRDS) is caused by lack of surfactant, commonly suffered by premature babies born before 28–32 weeks of gestation.
Hyaline membrane disease is an older term for IRDS. It is based on the pathological findings at autopsy of premature infants. The hyaline membranes were proteinaceous material in the damaged alveoli.
Congenital surfactant deficiency
Pulmonary alveolar proteinosis
Pulmonary alveolar proteinosis
Pulmonary alveolar proteinosis is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy , pulmonary infection, or environmental exposure to dusts or...

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

Infant respiratory distress syndrome

(IRDS).

External links

Mini review on Pulmonary Surfactant Minireview covering composition, function and pathologies of Pulmonary Surfactant

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