The endothelium, a protagonist in the pathophysiology of critical illness: focus on cellular markers

Abstract

The endotheliumis key in the pathophysiology of numerous diseases as a result of its precarious function in the regulation of tissue homeostasis. Therefore, its clinical evaluation providing diagnostic and prognostic markers, as well as its role as a therapeutic target, is the focus of intense research in patientswith severe illnesses. In the critically ill with sepsis and acute brain injury, the endothelium has a cardinal function in the development of organ failure and secondary ischemia, respectively. Cellular markers of endothelial function such as endothelial progenitor cells (EPC) and endothelialmicroparticles (EMP) are gaining interest as biomarkers due to their accessibility, although the lack of standardization of EPC and EMP detection remains a drawback for their routine clinical use. In this paper we will review data available on EPC, as a general marker of endothelial repair, and EMP as an equivalent of damage in critical illnesses, in particular sepsis and acute brain injury. Their determination has resulted in new insights into endothelial dysfunction in the critically ill. It remains speculative whether their determination might guide therapy in these devastating acute disorders in the near future.

Figure 1

Endothelial dysfunction in sepsis. In sepsis the reaction that has the aim of containing the infection derails and leads to a proinflammatory, procoagulant situation and endothelial dysfunction, finally resulting in the development of organ failure.

Figure 2

Endothelial dysfunction in SAH. SAH: subarachnoid hemorrhage. In subarachnoid hemorrhage, the development of delayed cerebral ischemia is a multifactorial process in which besides macrovascular vasospasm; thromboembolism, disturbed autoregulation, microvascular dysfunction, and cortical spreading depression are involved. Endothelial dysfunction is a key factor in the development of these processes. It is not clarified yet if local and general inflammation are causal factors or bystanders in the development of secondary ischemia.

Figure 3

Development of delayed cerebral ischemia after traumatic brain injury. SAH: subarachnoid hemorrhage; SIRS: systemic inflammatory response syndrome; TBI: traumatic brain injury. In traumatic brain injury the exact pathophysiology of secondary ischemia is not completely clarified. Besides cerebral mechanisms, extracerebral processes are also involved such as hypotension. On the other hand the endothelium seems to be a central player in its development.