Pathophysiology of Acute Respiratory Distress Syndrome and COVID-19 Lung Injury

Abstract

Acute respiratory distress syndrome (ARDS) is a rapidly developing non-cardiogenic pulmonary edema caused by pulmonary and systemic infections or sterile tissue injuries that evoke a severe lung-damaging host inflammatory response. The lung loses its normal gas exchange efficiency with disruption of the tight permeability characteristics of the alveolar capillary barrier. Interstitial and subsequent alveolar edema lead to alveolar collapse/de-recruitment, reduced lung compliance and greater pulmonary vascular resistance, often with marked regional heterogeneity in severity. Regional heightened stress applied to surrounding normal or less injured lung from edematous and collapsed regions along with associated barotrauma, volutrauma and atelectrauma with mechanical or extreme spontaneous ventilatory efforts further propagate injury in a vicious cycle called ventilator induced lung injury. Resulting arterial hypoxemia and hypercapnia arise from the creation of regions of shunt and low ventilation-perfusion (V A /Q) ratios, in addition to creation of high V A /Q and dead space areas by blood flow obstruction with thrombosis and/or high ventilating pressures. The pathophysiology of ARDS is discussed in this article and focuses on changes in the lung parenchyma and vasculature that reduce compliance, increase vascular resistance and compromise maintenance of dry normally compliant alveolar space by active alveolar fluid clearance and passive lymphatic fluid clearance from the lung interstitium. The COVID-19 pandemic that has emerged with the novel coronavirus, SARS-CoV-2, has generated a new form of severe acute lung injury that resembles ARDS in many of its features, but has different characteristics in its earliest stages leading to more profound hypoxemia and loss of dyspnea perception with less radiologically evident lung injury, not described before in ARDS. Understanding the pathophysiological features of ARDS and COVID-19 lung injury is critical to the best use of supportive therapies such as low tidal volume ventilation, supplemental oxygen concentrations, positive end-expiratory pressure (PEEP), permissive hypercapnia, prone positioning and neuromuscular blockade.

Severe acute respiratory disease in American mink (Neovison vison) experimentally infected with SARS-CoV-2

“…Our high-dose intratracheal inoculation likely contributed to the acute presentation of disease, and additional studies are necessary to better understand the course of SARS-CoV-2 infection in mink in relationship to dose, route of inoculation, and other emerging variants. Similar to the radiologic features described in humans, mink displayed bilateral ground glass opacities (30). However, unlike humans, these radiological features were not most severe in the gravitationally dependent regions (30).…”

“…Similar to the radiologic features described in humans, mink displayed bilateral ground glass opacities (30). However, unlike humans, these radiological features were not most severe in the gravitationally dependent regions (30). One theory explaining this atypical distribution is that the method of viral inoculation may have resulted in greater distribution in the caudal lung lobes as the virus was administered intratracheally in anesthetized subjects as opposed to a more passive inhalation of viral fomites.…”

Risk factors for COVID ‐19‐related mortality in hospitalized children and adolescents with diabetes mellitus: An observational retrospective cohort study

“…This finding is expected since the lung is one of the main target organs for SARS‐CoV‐2 infection and its damage results in greater risk of death for patients with COVID‐19. 34 Therefore, early signs of lung involvement, such as reduced oxygen saturation on admission, likely indicate greater disease severity. It is noteworthy that two relevant comorbidities in the context of diabetes, kidney disorders and obesity, were independent risk factors for fatal outcome.…”

Effectiveness of prone position in acute respiratory distress syndrome and moderating factors of obesity class and treatment durations for COVID-19 patients: A meta-analysis

“…Reduction of lung compliance increases the carbon dioxide dead space calculation, meanwhile, hypoxemia occurs as a result of ventilation-to-perfusion mismatching. COVID-19-related lung injury can be managed using the same principles of lung protective ventilation strategies as those in classic ARDS ( Swenson and Swenson, 2021 ). As a rescue therapy, the prone position significantly relieves lung compression which is squeezed by the gravity of the heart and abdominal organs in a supine position.…”