The 

primary cause of RDS is inadequate pulmonary surfactant. The

structurally immature and surfactant-deficient lung has ↓ compliance and a tendency to
atelectasis; other factors in preterm infants that ↑ the risk of atelectasis are decreased
alveolar radius and weak chest wall.

The pathophysiology of RDS can be described using LaPlace law, denoted as:

P=2T/R
where P is pressure, T is surface tension, and R is the radius. Laplace law describes
the relationship between the pressure difference across the interface of two static fluids
to the shape of the surface. As the surface tension increases at the alveolar level, the
amount of pressure required to maintain alveolar shape increases. With reduced
surfactant production, atelectasis occurs throughout the lung, causing reduced gas
exchange. Widespread and repeated atelectasis eventually damages the respiratory
epithelium, causing a cytokine-mediated inflammatory response. As pulmonary edema
develops as a result of the inflammatory response, increasing amounts of protein-rich
fluid from the vascular space to leak into the alveoli, which further inactivate
surfactant. Furthermore, many infants with RDS require mechanical ventilation, which
may have deleterious effects on the lung.
Overdistension of the alveoli during positive pressure ventilation leads to further
damage and inflammation. Besides, oxidative stress generated both by high oxygen
tensions from mechanical ventilation and inflammatory processes within the lung also
promotes the conversion of surfactant into an inactive form through protein oxidant
damage and lipid peroxidation. Thus RDS can cause hypoxemia through alveolar
hyperventilation, diffusion abnormality, ventilation-perfusion mismatch, intrapulmonary
shunting, or a combination of these mechanisms. This hypoxemia and tissue
hypoperfusion ultimately lead to increased anaerobic metabolism at a cellular level with
resultant lactic acidemia.