Acute respiratory distress syndrome (ARDS) is caused by a wide range of direct and indirect injuries that lead to severe inflammation and damage in the lungs. The core problem in ARDS is the disruption of the alveolar-capillary barrier, which normally allows oxygen to pass from the air sacs (alveoli) into the blood while keeping fluid out. When this barrier is damaged, fluid leaks into the alveoli, causing them to fill with protein-rich edema fluid. This flooding prevents oxygen from reaching the bloodstream effectively, leading to severe breathing difficulties.
Direct causes of ARDS include injuries that affect the lungs themselves, such as aspiration of stomach contents, viral or bacterial pneumonia, and inhalation of harmful substances. These insults trigger an intense inflammatory response in the lung tissue, damaging the delicate cells lining the alveoli and the blood vessels around them. This damage leads to increased permeability of the alveolar-capillary membrane, allowing fluid and immune cells to flood into the alveolar spaces.
Indirect causes involve systemic conditions that affect the lungs secondarily. For example, sepsis—a widespread infection in the body—can cause a massive inflammatory reaction that reaches the lungs. Other indirect causes include severe pancreatitis, major trauma, shock, and blood transfusions. These systemic insults release inflammatory mediators into the bloodstream, which then damage the lung’s blood vessels and alveoli, triggering the same cascade of injury seen in direct lung insults.
At the microscopic level, ARDS involves injury to both the endothelial cells lining the blood vessels and the epithelial cells lining the alveoli. This dual injury disrupts the basement membrane that supports these cells, further compromising the barrier function. The inflammatory response recruits immune cells like neutrophils, which release enzymes and reactive oxygen species that worsen tissue damage. The surfactant, a substance that normally keeps alveoli open and prevents collapse, becomes dysfunctional, leading to alveolar collapse and impaired gas exchange.
The accumulation of fluid and cellular debris in the alveoli causes widespread shunting of blood, meaning blood passes through the lungs without being properly oxygenated. This right-to-left intrapulmonary shunting is a hallmark of ARDS and contributes to the severe hypoxemia (low blood oxygen levels) seen in patients.
In addition to lung injury, ARDS can affect the heart, particularly the right ventricle, which pumps blood into the lungs. The increased resistance in the damaged and inflamed pulmonary vessels raises the workload on the right side of the heart. Factors like hypoxic vasoconstriction (narrowing of blood vessels due to low oxygen), elevated carbon dioxide levels, acidosis, and microthrombosis (tiny blood clots) all increase pulmonary vascular resistance. This can lead to right-sided heart dysfunction, which worsens the patient’s overall condition by impairing blood flow and oxygen delivery to the body.
Mechanical ventilation, often necessary to support breathing in ARDS, can itself contribute to lung injury and hemodynamic instability if not carefully managed. High pressures used to keep the lungs open may increase strain on the right heart and worsen inflammation.
In summary, ARDS is caused by a complex interplay of direct lung injuries and systemic inflammatory insults that damage the alveolar-capillary barrier, leading to fluid leakage, impaired oxygen exchange, and secondary effects on heart function. The underlying mechanisms involve endothelial and epithelial injury, inflammatory cell infiltration, surfactant dysfunction, and vascular changes that together create the severe respiratory failure characteristic of this syndrome.
