The role of the endothelium as a mediator of critical illness - Danny McAuley

Endothelium was once thought to be an inert organ. However, it plays an important role in multiple functions. These include coagulation, inflammation and determination of vascular permeability. He then gives a brief overview of the endothelial arrangement, function of the glycocalyx layer and how an injury causing a loss of the protective layer results in holes in the endothelium. The inflammatory cells enter via these holes and causes oedema in the affected organs leading to multiple pathologies. Danny then explains the role of endothelium in controlling cell barrier function. Activation of cortactin protein and the myosin light-chain kinase (MLCK) enzymes activate stress fibres resulting in pulling of endothelial cells thereby increasing its permeability. Danny discusses the role of endothelial dysfunction in acute respiratory distress syndrome (ARDS) at macrovascular, microvascular and molecular levels. Macrovascular thrombosis is related to an increase in severity of ARDS, pulmonary hypertension, and mortality. At a microvascular level there is a loss of vascularity and increased blood vessel thickness. At a microscopic level, endothelial cells appear swollen and damaged in ARDS. Endothelial dysfunction drives organ dysfunction and mortality. Changes in various endothelial markers like increased von Willebrand factor (vWF), decreased protein C and increased pulmonary dead space correlate with increased mortality. Studies show that endothelial dysfunction is a more specific and sensitive method to predict mortality of critically ill patients when compared to SOFA score, SAPS 2 score and WCC. Danny discusses ventilator strategies for endothelial cells in ARDS patients. Lowering the tidal volume of ventilators and employing recruitment manoeuvres are such strategies. Both of these cause a decrease in oedema by reducing endothelial permeability. He then shares the various potential pharmacological treatments for treating endothelial damage. These include statins and spingosine-1-phosphate (S1P). Different studies on the effect of statins in ARDS show contradicting result. However, targeted therapies can be designed by studying the phenotypes and molecular basis of ARDS in each patient. The role of the endothelium as a mediator of critical illness by Danny McAuley Finally, for more like this, head to our podcast page. #CodaPodcast