End Organ Damage

Sepsis is a complex pathological condition that precipitates significant dysfunction within tissues and organs, primarily due to a reduction in both the delivery and utilization of oxygen, which is fundamentally a result of cardiovascular impairment coupled with the phenomenon known as septic cardiomyopathy.

This acute pathological state, albeit reversible under certain circumstances, is closely associated with the release of various cytokines, prominently including tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1 β), which play critical roles in the inflammatory response. Furthermore, vascular dysfunction in the context of sepsis is marked by a troubling increase in capillary permeability and injurious effects on the endothelial lining, processes that are intricately regulated by the Angiopoietin-Tie2 signaling pathway.

The consequences of these pathological changes manifest as persistent vasodilation and pronounced endothelial dysfunction, conditions that are further aggravated by an overproduction of nitric oxide and a potential deficiency in vasopressin, both of which serve to complicate and hinder effective therapeutic interventions aimed at managing sepsis. Collectively, these mechanisms result in a significant reduction in blood flow, diminished cardiac output, and a range of systemic complications, all of which pose formidable challenges for clinicians engaged in the management of patients suffering from sepsis.

The predominant clinical feature indicative of cardiac dysfunction in the context of sepsis is contractile dysfunction, a condition that is heavily influenced by factors such as myocardial ischemia, direct depression of myocardial function, and dysfunction occurring at the mitochondrial level. The intricate interplay among these various mechanisms profoundly disrupts the delivery of oxygen and the perfusion of organs, ultimately culminating in a notable increase in both morbidity and mortality rates among individuals afflicted with sepsis. Thus, the multifaceted nature of sepsis necessitates a comprehensive understanding of its underlying pathophysiological processes to inform effective clinical strategies and interventions.

The underlying mechanism behind tissue and organ dysfunction in sepsis is the decreased delivery to and utilization of oxygen by cells as a result of hypoperfusion [1].

Hypoperfusion occurs due to the cardiovascular dysfunction that is seen in sepsis.

Septic cardiomyopathy varies from 18% to 60% in various studies. It is thought to be related to circulating cytokines, such as TNFα and IL-1β among others, which can cause depression of cardiac myocytes and an interference with their mitochondrial function.

The most important feature of septic cardiomyopathy is that:

It is acute in onset and reversible.
Second, the low left ventricular ejection fraction is accompanied by normal or low left ventricular filling pressures unlike in cardiogenic shock with increased left ventricular compliance [2].
Multiple research studies have shown both systolic and diastolic dysfunction with decreased stroke volumes and increased end-diastolic and end-systolic volumes in sepsis [3,4].