ARDS is a clinical syndrome associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung parenchyma. The triggering insult to the parenchyma usually results in an initial release of chemical signalsand other inflammatory mediators secreted by local epithelial and endothelial cells.
Neutrophils and some T-lymphocytesquickly migrate into the inflamed lung parenchyma 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, such as that caused by sepsis, causes endothelial dysfunction, fluid extravasation from the capillaries and impaired drainage of fluid from the lungs. Dysfunction of type II pulmonary epithelial cells may also be present, with a concomitant reduction in surfactantproduction. Elevated inspired oxygen concentration often becomes necessary at this stage, and 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 edemaincreases the thickness of the alveolo-capillary space, increasing the distance the oxygen must diffuse to reach blood, which impairs gas exchange leading to hypoxia, increases the work of breathing and eventually induces fibrosis of the airspace.
Edema and decreased surfactant production by type II pneumocytes may cause whole alveoli to collapse or to completely flood. This loss of aerationcontributes further to the right-to-left shunt in ARDS. As the alveoli contain progressively less gas, the blood flowing through the alveolar capillaries is progressively less oxygenated, resulting in massive intrapulmonary shunting. Collapsed alveoli and small bronchi do not allow gas exchange. It is common to see patients with a PaO
2 of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.
The loss of aeration may follow different patterns depending upon the nature of the underlying disease and other factors. These are 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 that are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.
Mechanical stress
Mechanical ventilation is an essential part of the treatment of ARDS. As loss of aeration and the underlying disease progress, the end tidal volume grows to a level incompatible with life. Thus, mechanical ventilation is initiated to relieve respiratory muscles of their work and to protect the usually obtunded patient's airways. However, mechanical ventilation may constitute a risk factor for the development—or the worsening—of ARDS.[7] Aside from the infectious complications arising from invasive ventilation with tracheal intubation, positive-pressure ventilation directly alters lung mechanics during ARDS. When these techniques are used the result is higher mortality through barotrauma.[7]
In 1998, Amato et al. published a paper showing substantial improvement in the outcome of patients ventilated with lower tidal volumes (Vt) (6 mL·kg−1).[7][9]This result was confirmed in a 2000 study sponsored by the NIH.[10] Both studies were widely criticized for several reasons, and the authors were not the first to experiment with lower-volume ventilation, but they increased the understanding of the relationship between mechanical ventilation and ARDS.
One opinion[who?] is that the forces applied to the lung by the ventilator may work as a lever to induce further damage to lung parenchyma. It appears that shear stress at the interfacebetween collapsed and aerated units may result in the breakdown of aerated units, which inflate asymmetrically due to the 'stickiness' of surrounding flooded alveoli. The fewer such interfaces around an alveolus, the lesser the stress. Even relatively low stress forces may induce signal transductionsystems at the cellular level, thus inducing the release of inflammatory mediators.[citation needed]
This form of stress is thought to be applied by the transpulmonary pressure(gradient) (Pl) generated by the ventilator or, better, its cyclical variations. The better outcome obtained in patients ventilated with lower Vt may be interpreted as a beneficial effect of the lower Pl. Transpulmonary pressure is an indirect function of the Vt setting on the ventilator, and only trial patients with plateau pressures (a surrogate for the actual Pl) were less than 32 cmH
2O(3.1 kPa) had improved survival.[citation needed]
The way Pl is applied on alveolar surface determines the shear stress to which lung units are exposed. ARDS is characterized by a usually inhomogeneous reduction of the airspace, and thus by a tendency towards higher Pl at the same Vt, and towards higher stress on less diseased units. The inhomogeneity of alveoli at different stages of disease is further increased by the gravitational gradient to which they are exposed and the different perfusion pressures at which blood flows through them. Finally, abdominal pressure exerts an additional pressure on inferoposterior lung segments, favoring compression and collapse of those units.[citation needed]
The different mechanical properties of alveoli in ARDS may be interpreted as having varying time constants—the product of alveolar compliance × resistance. A long time constant indicates an alveolus which opens slowly during tidal inflation, as a consequence of contrasting pressure around it, or altered water-air interface inside it—loss of surfactant, flooding.[citation needed]
Slow alveoli are said to be "kept open" using positive end-expiratory pressure, a feature of modern ventilators which maintains a positive airway pressure throughout the whole respiratory cycle. A higher mean pressure cycle-wide slows the collapse of diseased units, but it has to be weighed against the corresponding elevation in Pl/plateau pressure. Newer ventilatory approaches attempt to maximize mean airway pressure for its ability to "recruit" collapsed lung units while minimizing the shear stress caused by frequent openings and closings of aerated units. The prone position also reduces the inhomogeneity in alveolar time constants induced by gravity and edema. If clinically appropriate, mobilization of the ventilated patient can assist in achieving the same goal.[citation needed]
Stress Index
