Acute Respiratory Distress Syndrome (ARDS)

  • Acute Respiratory Distress Syndrome (ARDS) is a syndrome of rapid-onset dyspnea and hypoxemia associated with diffuse bilateral pulmonary infiltrates on chest radiography that can progress to outright respiratory failure. Acute Lung Injury (ALI) displays the same etiologies and pathogenesis as ARDS but is considered to be a less severe form of the disease with better outcomes; however, patients with ALI can progress to develop outright ARDS.
  • A wide variety of disease processes can result in ARDS although the common precipitating factor appears to be either direct or indirect injury to the pulmonary parenchyma. Common causes of direct injury include pneumonia, aspiration, Chest trauma, or inhalation of toxins. The most common indirect cause of ARDS is sepsis although acute pancreatitis can also result in disease. Given that the etiological basis of ARDS is injury to the pulmonary parenchyma, cardiogenic causes of pulmonary edema, such as left-sided heart failure must be ruled out for a proper diagnosis of ARDS.
  • Overview
    • Whatever the precipitating injury, breakdown of the alveolar membrane is the root cause of ARDS. Damage to the alveolar membrane results in a sequence of events which progresses through three distinct phases described below.
  • Acute Phase
    • The acute phase of ARDS follows within hours after the precipitating injury and is characterized by a damage to the pulmonary capillaries and the Type I Pneumocytes which compose the alveolar membrane. This results in a sudden increase in vascular permeability that allows leakage of plasma fluid and proteins into the alveoli, yielding rapid pulmonary edema. In addition, the acute phase of ARDS is characterized by the presence of high concentrations of inflammatory cytokines within the lung, such as TNF-alpha and IL-8 which serve to induce a rapid inflammatory response characterized by an influx of neutrophils into the lungs. The presence of neutrophils likely leads to further damaging of the alveolar membrane, compounding the initial insult.
    • The rapid-onset pulmonary edema of ARDS, resulting in dyspnea, can generate areas of right-left shunt and ventilation-perfusion defects within the lung which are likely the pathophysiologic source of hypoxemia. The presence of fluid within the alveoli also results in a significant decrease in lung compliance, yielding a restrictive pattern of pulmonary function that increases the work of breathing. Patients often respond by becoming tachypnic but may decompensate, ultimately resulting in respiratory failure. The bilateral diffuse pulmonary infiltrates seen in ARDS are also due to the pulmonary edema, although this finding cannot be diagnostically distinguished from other sources pulmonary edema.
  • Late Phase
    • The acute phase of ARDS lasts roughly 7 days and is followed by a healing phase that lasts for 3-4 weeks. With modern critical care support most patients survive the acute phase and slowly regain respiratory function, characterized by improving hypoxemia, dyspnea, and radiological findings. However, as described in the morphology section below, healing can involve significant fibrosis of the pulmonary parenchyma which can result in lingering respiratory difficulty and an increased risk for future morbidity and mortality.
  • Overview
    • The morphological basis of ARDS is known as "Diffuse Alveolar Damage" and evolves along the acute and late phases described in the pathogenesis section above.
  • Acute Phase
    • The acute phase of ARDS manifests is typified by fluid within alveoli along with characteristic "Hyaline Membranes" that represent aggregations of leaked plasma proteins along with necrotic cellular debris. Small vessels and pulmonary capillaries appear congested, often possessing small thrombi, while necrosis of type I pneumocytes may be observed. Additionally, alveoli often contain some blood due to hemorrhage and numerous neutrophils, representing the inflammatory component of the disease.
  • Late Phase
    • The late phase of ARDS is characterized by proliferation of type II pneumocytes, likely dividing in an attempt to replace damaged type I pneumocytes. Alveolar edema slowly regresses along with a replacement of neutrophils with mononuclear cells which eventually leave. Over time, some patients will display significant fibrosis of their pulmonary interstitium that can yield significant distortion of the pulmonary architecture, leading to honeycomb lung.
Clinical Consequences
  • As described above, ARDS results in the rapid onset of dyspnea and hypoxemia together with the presence of bilateral diffuse pulmonary infiltrates on chest radiography. These symptoms are often associated with tachypnea and may last up to a week. In those who do not succumb to respiratory failure, a late phase characterized by improving lung function ensues; however, many patients never fully recover and may display chronic respiratory dysfunction.