ARDS can be initiated by various distinct conditions that lead to a common pathophysiological pathway. The triggering events are grouped into two classes: direct ‘pulmonary’ and indirect ‘extrapulmonary’ conditions. The direct causes include various conditions that injure the lung parenchyma, including pneumonia, pulmonary contusion due to trauma, aspiration and inhalation, or ingestion of toxic agents (table 2). The most frequent indirect insult is sepsis syndrome (a common and highly lethal cause of ARDS), but this group also includes acute pancreatitis, overdose of certain drugs (opiates or thiazides), disseminated intravascular coagulation, and multiple blood product transfusions (hypertransfusion). Despite the variety of triggers, the resulting ARDS, in its later stages, shows a uniform clinical and pathological pattern, even though the pathophysiological routes and mechanisms may differ depending on the event that injures the lungs.

AECC definition 1994 Berlin definition 2012
Acute onset Onset within 1 week of a known clinical insult or new or worsening respiratory symptoms
Bilateral infiltrates observed on frontal chest radiograph Bilateral opacities – not fully explained by effusions, lobar/
lung collapse or nodules
PAOP less than 18 mmHg (if measured) or no clinical evidence of increased left atrial pressure Respiratory failure not fully explained by cardiac failure or fluid overload. Objective assessment (e.g. echocardiography) required to exclude hydrostatic oedema if no risk factor present
ALI: PaO2/FIO2 <300 mmHg All grades with a PEEP or CPAP of ≥5 cmH2O
ARDS: PaO2/FIO2 <200 mmHg Mild ARDS: 200 mmHg Moderate ARDS: 100 mmHg Severe ARDS: PaO2/FIO2≤100 mmHg
No risk factor included If no risk factor present, need to objectively rule out
hydrostatic oedema
Table 1 – Comparison of the American–European Consensus Conference (AECC) and Berlin definitions of acute
respiratory distress syndrome (ARDS). PAOP: pulmonary artery occlusion pressure; ALI: acute lung injury; PaO2:
arterial oxygen tension; FIO2: inspiratory oxygen fraction; PEEP: positive end-expiratory pressure; CPAP: continuous
positive airway pressure.

The acute phase of ARDS is characterised by injury to the alveolar–capillary barrier, with disruption leading to increased permeability (‘leakiness’). Leukocytes accumulate in the pulmonary capillaries and invade the airspaces. The consequences include inflammatory vasoconstriction (in contrast to inflammation-induced vasodilatation in the systemic circulation), reduced compliance (greater ‘stiffness’) of the lungs and atelectasis (collapse of alveoli rendering them airless) due to loss of the surfactant that lines and normally stabilises alveoli, reducing surface tension of the alveolar lining fluid. The consequent respiratory failure is aggravated by severe ventilation/perfusion mismatching, with some perfused alveoli no longer receiving any ventilation (‘shunt’), while others are ventilated but not perfused (‘dead space’).

Histopathologically, three phases are recognised during the evolution of ARDS: 1) an exudative early phase which results from diffuse alveolar damage and endothelial injury; 2) a proliferative phase which ensues about 7–14 days after the injury, incorporating repair of the damaged alveolar structure and re-establishment of the barrier function, together with proliferation of fibroblasts; 3) a fibrotic phase with chronic inflammation and fibrosis of the alveoli, which follows in some patients.

Direct (pulmonary) injury Indirect (extrapulmonary) injury
Pneumonia (bacterial, viral, fungal) Severe sepsis
Gastric aspiration Shock
(Near-) Drowning Multiple transfusion (including TRALI)
Severe thoracic trauma/pulmonary contusion Severe non-thoracic trauma
Reperfusion pulmonary oedema (e.g. after lung
Fat embolism Disseminated intravascular coagulation
Smoke and toxic gas inhalation Drug overdose (i.e. opiates, paraldehyde)
Table 2 – Main triggers of acute respiratory distress syndrome (ARDS). TRALI: transfusion-related acute lung injury.

See the entire Acute respiratory distress syndrome Chapter