In pulmonary alveolar proteinosis (PAP), the alveoli fill with PAS-positive, lipid-rich material. The most common pathogenic mechanism of acquired PAP involves:

• A Loss of CFTR function causing impaired mucociliary clearance
• B Deficiency of alpha-1 antitrypsin causing protease imbalance
• C Loss of SP-B (surfactant protein B) due to genetic mutation
• D Autoantibodies against GM-CSF (granulocyte-macrophage colony-stimulating factor), causing alveolar macrophage dysfunction and impaired surfactant catabolism ✓

Explanation

Acquired (autoimmune) PAP accounts for ~90% of all PAP cases and is caused by neutralizing IgG autoantibodies against GM-CSF. GM-CSF is required for alveolar macrophage differentiation and their capacity to catabolize surfactant phospholipids and proteins. Without effective GM-CSF signaling, alveolar macrophages accumulate incompletely processed surfactant material (periodic-acid-Schiff positive, with characteristic dense bodies on EM), which fills the alveoli. Treatment includes whole lung lavage and inhaled recombinant GM-CSF. SP-B mutations cause hereditary PAP in neonates.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.