Acute respiratory distress syndrome pathophysiology

Overview
Acute respiratory distress syndrome primarily results from the diffuse inflammation of lung parenchyma. Loss of aeration can cause fundamental changes in inflammation amplification and progression.

Pathophysiology

 * ARDS is characterized by a diffuse inflammation of lung parenchyma.
 * The triggering insult to the parenchyma usually results in an initial release of cytokines and other inflammatory mediators, secreted by local epithelial and endothelial cells.
 * Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung parynchema and contribute in the amplification of the phenomenon.
 * Typical histological presentation involves diffuse alveolar damage and hyaline membrane formation in alveolar walls.
 * Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.

Inflammation

 * Inflammation alone, as in sepsis, causes:
 * Endothelial dysfunction
 * Fluid extravasation from the capillaries
 * Impaired drainage of fluid from the lungs


 * Dysfunction of type II pulmonary epithelial cells may also be present, with a concomitant reduction in surfactant production.
 * Elevated inspired oxygen concentration often becomes necessary at this stage, and they may facilitate a 'respiratory burst' in immune cells.
 * In a secondary phase, endothelial dysfunction causes cells and inflammatory exudate to enter the alveoli
 * This pulmonary edema increases the thickness of the alveolo-capillary space, increasing the distance the oxygen must diffuse to reach blood.
 * This impairs gas exchange leading to hypoxia, increases the work of breathing, eventually induces fibrosis of the airspace.
 * Rdema and decreased surfactant production by type II pneumocytes may cause whole alveoli to collapse, or to completely flood. This loss of aeration contributes further to the right-to-left shunt in ARDS.
 * As the alveoli contain progressively less gas, more blood flows through them without being oxygenated resulting in massive intrapulmonary shunting.
 * Collapsed alveoli (and small bronchi) do not allow gas exchange. It is not uncommon to see patients with a PaO2 of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.
 * The loss of aeration may follow different patterns according to the nature of the underlying disease, and other factors. In pneumonia-induced ARDS, for example, large, more commonly causes relatively compact areas of alveolar infiltrates.
 * Usually distributed to the lower lobes, in their posterior segments, and they roughly correspond to the initial infected area.
 * In sepsis or trauma-induced ARDS, infiltrates are usually more patchy and diffuse. The posterior and basal segments are always more affected, but the distribution is even less homogeneous.
 * Loss of aeration also causes important changes in lung mechanical properties. These alterations are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.