Acute respiratory distress syndrome pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Brian Shaller, M.D. [2]

Overview[edit | edit source]

ARDS is a syndrome of inflammation and increased permeability with the lung parenchyma that leads to loss of type I pneumocytes, impaired gas exchange, inappropriate cell proliferation within alveoli, and, in survivors, fibrosis.

Pathophysiology[edit | edit source]

ARDS typically develops within 24 to 48 hours of the provoking illness or injury and is classically divided into three phases:^[1][2][3]

• Exudative phase (within 5 to 7 days): Systemic inflammation results in increased permeability of the alveolar-capillary barrier and leads to the formation of hyaline membranes along alveolar walls, accumulation of proteinaceous exudate within the alveolar air spaces (non-cardiogenic pulmonary edema), and extravasation of inflammatory cells (predominantly neutrophils) into the lung parenchyma, leading to extensive alveolar damage and, occasionally, diffuse alveolar hemorrhage
• Proliferative phase (within 7 to 21 days): Fibroblast proliferation, collagen deposition, and early fibrotic changes are observed within the pulmonary interstitium as alveolar exudate and hyaline membranes begin to be absorbed
• Fibrotic phase (within several weeks): Many patients with ARDS will develop some degree of pulmonary fibrosis, of which at least one-quarter will go on to develop clinically apparent fibrotic lung disease with a restrictive ventilatory defect on pulmonary function tests;^[4] the development and extent of pulmonary fibrosis in ARDS correlates with an increased mortality risk^[5]

Genetics[edit | edit source]

The role of genetics in the development of ARDS is an ongoing area of research. While studies have demonstrated associations between certain genetic factors (including single nucleotide polymorphisms and allelic variants of angiotensin-converting enzyme) and increased susceptibility to the development of ARDS, the nature and implications of these relationships remain uncertain.^[6][7][8]

Pathology[edit | edit source]

On gross pathology, the following are characteristic findings of ARDS:

• Firm, boggy, and dusky lungs
• Generally increased weight compared to healthy lungs due to edema

On microscopic histopathological analysis, the following are characteristic findings of ARDS:

• Lung parenchyma demonstrates:
  • Hyaline membranes lining the alveolar air spaces
  • Edema fluid within alveoli and the interstitium
  • Shedding of type I pneumocytes and proliferation of type II pneumocytes
  • Infiltration of polymorphonuclear and other inflammatory cells into the interstitial and alveolar compartments,
  • Thrombosis and obliteration of pulmonary capillaries
  • Hemorrhage into alveoli
• Features specific to the underlying disease process (e.g., pneumonia or aspiration pneumonitis)
• With progression, alveolar infiltrates are reabsorbed and the inflammatory milieu is replaced by increased collagen deposition and proliferating fibroblasts, culminating in interstitial fibrosis

References[edit | edit source]