Intrapulmonary bronchopulmonary anastomoses in COVID-19 respiratory failure

Abstract

The spread of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) has led to a devastating and world-wide pandemic disease known as the coronavirus disease (COVID-19). COVID-19 causes acute hypoxic respiratory failure (COVID-ARF), a major cause of mortality and morbidity, with an incompletely understood pathophysiologic mechanism. Gattinoni and colleagues noted that patients with COVID-ARF patients have lung disease that is often characterised by a remarkable dissociation between relatively well-preserved lung mechanics, including lung compliance, and severe hypoxemia [1].

Understanding COVID-19 susceptibility and presentation based on its underlying physiology

“…Once again, autopsy studies proved instrumental to fuel important functional insights into underlying mechanisms. Specifically, analyses aimed to define the architecture and microanatomy of blood vessels in the distal lungs from serial hematoxylin and eosin (H&E) sections and subsequent computed three-dimensional (3-D) image reconstruction revealed patency of prominent intrapulmonary bronchopulmonary anastomoses (IBAs) in lungs of COVID-19 patients ( 14 ). These IBAs connect pulmonary arteries and bronchial arteries and therefore allow the deoxygenated blood to bypass the alveolocapillary compartment by creating a right-to-left shunt with profound hypoxemia.…”

Endotheliitis, Shunts, and Ventilation–Perfusion Mismatch in Coronavirus Disease 2019: A Literature Review of Disease Mechanisms

“…Additional investigations have reported the presence of prominent intrapulmonary bronchopulmonary anastomoses (IBAs) between the pulmonary and bronchial arteries as a potential source of a right-left shunt, which is not exclusive to COVID-19 infection and has been reported in idiopathic pulmonary hypertension and chronic thromboembolic pulmonary hypertension [ 50 ]. These IBAs predominate in fetal life and are obliterated at birth, but may persist in the context of the disease [ 51 , 52 ].…”

“…The underlying inflammatory process has been shown to induce recruitment of bronchopulmonary anastomoses, with the right-left shunt preventing the alveolar-capillary network and impairing gas exchange [ 55 , 56 ]. This shunt further reduces distal perfusion, leading to intractable hypoxemia and death [ 50 ]. Viral endocytosis reduces the availability of ACE2 and angiotensin II as regulators, which in this condition has a limited vasoconstrictor potential and downregulates ACE (cleavage effect mediated by the protease ADAM 17) [ 57 ].…”

Pathophysiology of coronavirus-19 disease acute lung injury

“…On the contrary, in patients with COVID-19 pneumonia – particularly in the initial phases – the severity of hypoxaemia is more severe compared to what can be expected from the estimated anatomical shunt [ 12 , 13 ▪ ]. This discrepancy can be explained by the fact that a primary alteration of pulmonary perfusion leads to profound ventilation/perfusion inequalities [ 12 ] with higher prevalence of compartments with very low ventilation/perfusion ratio, which seems to be determined by the interaction between the higher cardiac output due to possible intrapulmonary [ 14 ] and splanchnic shunts [ 15 ], and the hyperperfusion of poorly ventilated compartments. These abnormalities can worsen further if inappropriate mechanical ventilation leads to hypoventilation (very low tidal volumes in normal size lung volumes) and, together with an absolute increase in cardiac output [ 16 ], this combination lowers the overall ventilation/perfusion ratio and worsens the hypoxaemia that can be explained even assuming limited hypoxic vasoconstriction [ 11 , 12 , 17 ].…”