Surfactant
treatment
SURFACTANT
Pulmonary surfactant, a
lipid-protein complex that modulates surface tension at the
respiratory air–liquid interface to stabilise bronchoalveolar
structure, plays a fundamental role in lung development and
respiration.
RDS,
characterised by a deficiency of surfactant, affects over
half of premature infants and accounts for the largest single
group of babies admitted to NICUs.
For a surfactant to function
effectively two properties are essential: good compressibility
to reach low surface tensions under pressure, on expiration;
rapid interface adsorption, on inspiration.
Composition
Surfactant is composed mainly
of:
- Phospholipids
- Neutral lipids
- Proteins
Phospholipids,
which make up over 80% of surfactant complexes, play a major
biophysical role in surfactant function because of their ability
to form stable interfacial monomolecular films that are able
to achieve and sustain very low surface tensions.
The most important phospholipids in mature surfactant are
phosphatidylcholine (PC) and phosphatidylglycerol (PG). The
majority of the PC has saturated fatty acids (i.e. disaturated).
The primary saturated fatty acid is palmitic acid. Therefore
the molecule is called Dipalmitoyl phosphatidylcholine
(DPPC). This is the major component of mature surfactant.
The neutral lipids
are cholesterol and free fatty acids.
Surfactant complexes contain
approximately 8% by weight of specific proteins.
Four surfactant-associated proteins have been identified:
Surfactant protein A
Main role is thought to be host defence – increases
phagocytosis of bacteria. It is known that mice without SP-A
can breathe normally but are very prone to infections. SP-A
has a number of other effects including structuring tubular
myelin. SP-A is also water-soluble and is the major protein
by weight in surfactant.
Surfactant protein D
SP-D has no surfactant like activities but is involved
in the immune activity of the lung. SP-D is also water-soluble.
Surfactant protein B and Surfactant protein C
These two proteins are involved in spreading of surfactant
phospholipids and adsorption of phospholipids.
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Surfactant
production and release
Surfactant is produced by
type II cells within the alveoli. The distinguishing
feature of these cells is the presence of lamella bodies.
These are storage granules for surfactant and secretion from
the cell is by exocytosis of these bodies (rupture through
the cell wall).
The phospholipids are produced by intracellular mechanisms
(probably the endoplasmic reticulum and Golgi system) prior
to packing into the lamella bodies.
Surfactant release by exocytosis
from these lamella bodies can be stimulated by a number of
factors:
- Gas entering the lung (as at birth)
- Stretching of the alveolar epithelium
(e.g. during inspiration)
- Adrenergic (adrenaline/noradrenaline)
stimulation
- Prostaglandins
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Surfactant
cycle
A small amount of surfactant
is lost to the airways or by degradation by alveolar macrophages.
Surfactant is also broken down within the alveolar fluid and
the by-products absorbed and recycled.
In a mature lung the majority of molecules seem to be recycled
whole and thus new surfactant synthesis only contributes a
small amount to the surfactant pool.
This process is not so efficient in the developing lung and
therefore surfactant turnover is reduced.
Once secreted from the lamellar
bodies into the aqueous layer, surfactant forms a number of
structures, one of which is known as tubular myelin
(TM). This has a structure of crossing bilayers.
If SP-B (and SP-A) and Ca2+ are
present in vitro tubular myelin structures can be formed.
The presence of tubular
myelin is related to the ability of surfactant to adsorb quickly
to the air-water interface.
However mice with no SP-A (no tubular myelin) can still breathe
normally which implies there may be a number of adsorption
mechanisms.
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“Squeeze
out” hypothesis
The first element of film
formation is movement of protein-lipids close to the air-liquid
interface. Structures like tubular myelin and others are thought
to facilitate movement of large numbers of molecules. These
structures then become associated with the existing film and
form ‘surfactant reservoirs’.
The final step is the adsorption
of lipids to the interface – this step is thought to
be catalysed by SP-B and SP-C,
the molecular shape of these proteins is important for this
action.
The exact molecular mechanisms are yet to be determined –
there are a number of inconsistencies to the squeeze out model.
However, we do know that the surfactant proteins B and C are
important modulators of the activity of the phospholipids.
Lack of SPB caused by genetic
mutation is a lethal mutation. Currently, it can only be treated
by a lung transplant.
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Background
reading
- Van Golde LMG et al. The pulmonary surfactant system.
News in Physiological Sciences 1994; 9: 13-20.
- Schürch S et al. Surface activity of lipid extract
surfactant in relation to film area compression and collapse.
J Appl Physiol 1994 Aug; 77(2): 974-986 (PubMed).
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