Diffuse alveolar damage (ARDS)
- Lesion
In ARDS the alveolar lining and capillaries are injured. Protein-rich fluid leaks, dead cells and fibrin form hyaline membranes, and the lung may scar.
What it is
Acute lung injury is the sudden onset of hypoxaemia with bilateral edema that is not due to heart failure; ARDS is its severe clinical form. Its tissue pattern is diffuse alveolar damage (DAD): leaky capillaries, dead pneumocytes and hyaline membranes, followed by an organising phase. Sepsis, diffuse lung infection, gastric aspiration and severe trauma cause most cases.
Structure
- Gross (acute): heavy, firm, red, boggy lungs; patchy ground-glass and consolidation on imaging.
- H&E, exudative phase: congested capillaries, interstitial and alveolar edema, fibrin, scattered neutrophils, and eosinophilic hyaline membranes on alveolar walls.
- H&E, organising phase: plump hyperplastic type II pneumocytes, loose fibroblastic tissue in the interstitium and airspaces.
- Late: interstitial fibrosis in a minority of survivors.
Step by step
- A direct (aspiration, pneumonia) or indirect (sepsis, trauma, pancreatitis) insult injures pneumocytes and endothelium.
- Alveolar macrophages release TNF, IL-1 and chemokines; endothelium expresses adhesion molecules and procoagulants.
- Neutrophils stick, migrate into the alveoli and release proteases, oxidants and NETs, injuring more cells.
- Leaky capillaries flood the interstitium and alveoli with protein-rich fluid.
- Type II cells die, surfactant is lost; fibrin and cell debris settle as hyaline membranes.
- Patchy injury leaves perfused but unventilated areas: shunt and hypoxaemia that resists oxygen.
- If the trigger ends, macrophages clear debris and TGF-β drives repair; type II cells regrow the lining, or fibrosis follows.
The phases of diffuse alveolar damage
| Phase | Time | What the pathologist sees | Consequence |
|---|---|---|---|
| Exudative | First days to a week | Edema, fibrin, neutrophils, hyaline membranes | Shunt, stiff lungs |
| Proliferative (organising) | From the second week | Type II pneumocyte hyperplasia, fibroblasts in septa and spaces | Slow improvement or progression |
| Fibrotic or resolved | Weeks to months | Interstitial fibrosis, or restored lining | Recovery or chronic restriction |
Markers
- Hyaline membranes
- Type II pneumocyte hyperplasia
Clinical notes
- Profound dyspnoea and tachypnoea, then hypoxaemia refractory to oxygen, diffuse bilateral infiltrates, stiff lungs needing high ventilator pressures.
- Mortality is high and rises with severity; deaths come mostly from sepsis and multiorgan failure.
- Most survivors recover function; some keep fibrosis. Risk is higher with alcohol use disorder and smoking.
Test yourself
Think of the answer, then tap the question to see it.
What are hyaline membranes made of?
Fibrin-rich, protein-rich edema fluid mixed with the debris of necrotic alveolar epithelial cells.
Which four conditions cause more than half of ARDS cases?
Sepsis, diffuse pulmonary infection, gastric aspiration and mechanical trauma including head injury.
Why is the hypoxaemia of ARDS refractory to oxygen?
Many alveoli are flooded or collapsed but still perfused, so blood shunts past them; extra inspired oxygen cannot reach that blood.
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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Acute Respiratory Distress Syndrome (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.