Surfactant And Infant Respiratory Distress Syndrome Flashcards
Review of properties of water
Highly polarized bonds w/ high electronegativity
- partial positive charges on hydrogen
- partial negative charges on oxygen
Has a tetrahedral geometry
Has high surface tension compared to other water containing molecules
Boiling point and surface tension of water is much higher than most comparable substances
Surface tension w/ respect to water molecules
Intermolecular attraction between water molecules is increased with water molecules that are exposed to air compared to the ones not.
- being exposed to air causes the water molecules to form much stronger hydrogen bonds
- also generates a net inward force causing surface molecules to contract and be resistance to stretching
behaves like an elastic membrane
How does surface tension affect alveolar function?
Water will attempt to minimize its surface area whenever it comes in contact w/ air or hydrophobic molecules
If no surfactant is present in alveoli, the alveoli will collapse easier since the water on the alveoli will collapse to minimize its surface area as quick as possible
Lung surfactant
90% lipid and 10% protein combination that contains
- phospholipids
- DPPC
- Proteins
- unsaturated
- Phosphatidylglycerols
Helps prevent intermolecular hydrogen bonding between water molecules and lower surface tension in alveoli
- prevents alveoli from collapsing since surface tension is DECREASED
Function of lung surfacing on breathing cycles
1) allows for alveoli to expand easily upon inhalation
- done by allowing full inflation and decreases surface tension to about 30 dynes (compared to 70 dynes w/out surfactant)
2) Allows the alveoli to not collapse during exhalation
- surfactant lipids allow surface tension to decrease to 5 dynes, but NOT 0 dynes which is what would happen if no surf ant is present
- collapse occurs at 0 dynes
note that the surface tension does not increase easily with surfactant and does not reach 0, preventing collapse and allowing easy expansion during inhalation
Where is lung surfactant generated and how?
Is created in type 2 alveolar cells
Steps:
1) surfactant lipids and proteins are transported and stored in the cytoplasm in structures called lamellar bodies within the type 2 cells
2) lamellar bodies are exocytosis to fuse into plasma membrane
3) surfactant in the plasma membrane helps form tubular myelin (reservoir for surfactant during alveolar respiration)
4) tubular myelin helps insert surfactant into air-water surface when needed
5) during expiration only, surfactant w/ exogenous debris is removed and recycled by type 2 cells
SP-A and SP-D proteins
Huge hydrophilic glycoproteins found in surfactant
Functions
- involved in innate host defenses by agglutination pathogens allowing better phagocytosis via macrophages
- possess antimicrobial properties
- helps regulate inflammation by binding to TNF-a, IL1/6 receptors on epithelium and immune cells
SP-B and SP-C proteins
Small hydrophobic proteins in surfactant that work w/ surface activity
Functions
- interact strongly w/ phospholipids
- prevents collapse of alveoli
- SP-B is essential to breathing for infants and will develop lethal neonatal respiratory distress if absent*
- SP-C is not essential to breathing but will lead to acute/chronic Lung diseases in infancy, also are worse when mutated compared to nonexpressed*
Infant respiratory distress syndrome (IRDS)
Serious clinical problem that is caused by absence of SP-B proteins
Most common cause of neonatal mortality
And high incidence in premature births
To treat
- oxygenation
- surfactant replacement therapy
- ventilation
What is the minimal requirement L/S ratio for functional lungs?
2: 1
- lecithin: sphingomyelin
This ratio suggests mature surfactant production
- note: that sphingomyelin numbers don’t increase much and are relatively constant, however the lecithin numbers do spike usually around 35th week
This ratio is complete by 35th week, otherwise develops IRDS
How do you treat RDS?
Before birth:
- give mother corticosteroid injections if possible ( best is betamethasone)
After birth:
- supportive care and oxygen
- artificial surfactant injections