A term newborn born to a mother with meconium-stained amniotic fluid develops respiratory distress within 2 hours of birth. Chest X-ray shows patchy infiltrates with hyperinflation. What is the most common mechanism of lung injury in meconium aspiration syndrome?

## Pathophysiology of Meconium Aspiration Syndrome **Key Point:** Surfactant inactivation combined with mechanical airway obstruction is the primary mechanism of lung injury in MAS, not direct chemical toxicity. ### Mechanism of Injury Meconium aspiration causes injury through multiple pathways: 1. **Surfactant inactivation** — meconium contains bile acids, cholesterol, and other lipids that directly inactivate pulmonary surfactant, reducing its surface tension-lowering ability 2. **Mechanical obstruction** — meconium particles occlude small airways, causing ball-valve obstruction with air trapping distal to the blockade 3. **Inflammatory cascade** — aspiration triggers release of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) leading to secondary pneumonitis ### Clinical Correlation The combination of surfactant inactivation and airway obstruction explains the characteristic radiographic findings: - Patchy infiltrates (areas of atelectasis from obstruction) - Hyperinflation (air trapping distal to obstructed airways) - "Barrel chest" appearance on physical exam **Clinical Pearl:** Exogenous surfactant administration (lung lavage with dilute surfactant) has become standard therapy precisely because surfactant inactivation is the dominant pathophysiologic mechanism. **High-Yield:** The degree of surfactant inactivation correlates with severity of respiratory distress — infants with thicker, more concentrated meconium have worse outcomes. ### Why Hyperinflation Occurs Ball-valve obstruction allows air entry during inspiration but prevents egress during expiration, leading to progressive air trapping and hyperinflation — this is why MAS often progresses despite initial mild presentation.