Microvascular dysfunction in septic and dengue shock: Pathophysiology and implications for clinical management

Angela McBride,James F Fraser,Sophie Yacoub,Nchafatso G Obonyo,Ho Q Chanh

doi:10.21542/gcsp.2020.29

Abstract

The microcirculation comprising of arterioles, capillaries and post-capillary venules is the terminal vascular network of the systemic circulation. Microvascular homeostasis, comprising of a balance between vasoconstriction, vasodilation and endothelial permeability in healthy states, regulates tissue perfusion. In severe infections, systemic inflammation occurs irrespective of the infecting microorganism(s), resulting in microcirculatory dysregulation and dysfunction, which impairs tissue perfusion and often precedes end-organ failure. The common hallmarks of microvascular dysfunction in both septic shock and dengue shock, are endothelial cell activation, glycocalyx degradation and plasma leak through a disrupted endothelial barrier. Microvascular tone is also impaired by a reduced bioavailability of nitric oxide. In vitro and in vivo studies have however demonstrated that the nature and extent of microvascular dysfunction as well as responses to volume expansion resuscitation differ in these two clinical syndromes. This review compares and contrasts the pathophysiology of microcirculatory dysfunction in septic versus dengue shock and the attendant effects of fluid administration during resuscitation.

Highlights

The microcirculation is the terminal vascular network of the systemic circulation, whose primary function is to distribute oxygen to, and remove metabolic by-products from living cells
The dengue non-structural 1 (NS1) protein, a viral glycoprotein secreted by infected cells, has been shown to cause an increase in endothelial permeability leading to vascular leakage[50]
Summary and future directions Impairment in perfusion, tone and barrier-function of the microcirculation is central to the pathogenesis of both septic shock and dengue shock; but it is clear from in vitro and clinical studies that the nature and extent of dysfunction differs between the syndromes

Summary

Introduction

The microcirculation is the terminal vascular network of the systemic circulation, whose primary function is to distribute oxygen to, and remove metabolic by-products from living cells. In both septic shock and dengue shock, the common hallmarks of microvascular dysfunction are endothelial cell activation and glycocalyx degradation leading to plasma leak through a disrupted endothelial barrier, together with reduced nitric oxide bioavailability leading to impaired microvascular tone[19,20,21,22].

Results

Conclusion