Pathophysiology of sepsis-induced cardiovascular and renal dysfunction
The factors causing sepsis-induced organ dysfunction remain unclear due to the complex pathophysiology of sepsis that changes as the response to the infection progresses. There is evidence that redox homeostasis is disrupted in sepsis resulting in oxidative stress, which together with excessive inflammation is thought to cause mitochondrial, endothelial and microvascular dysfunction, resulting in vasoplegia, inflammation-mediated tissue injury, tissue hypoxia and multi-organ dysfunction (Joffre & Hellman, 2021) (Lankadeva, Okazaki, Evans, Bellomo & May, 2019).
Hypotension secondary to peripheral vasodilatation is a hallmark of sepsis that is treated with aggressive fluid resuscitation and vasopressor therapy to restore target mean arterial pressure (Rhodes et al., 2017). Reduced vascular responsiveness to noradrenaline, the primary vasopressor used clinically, is common in sepsis resulting in persistent and sometimes refractory hypotension (Annane et al., 1998), which, in itself, can result in tissue hypoperfusion and hypoxia, mitochondrial dysfunction and multi-organ failure.
Indeed, tissue hypoperfusion and hypoxia in the renal medulla are critical pathophysiological features of ovine hyperdynamic sepsis that precede the development of acute kidney injury (AKI) by 8 to 12-h (Calzavacca, Evans, Bailey, Bellomo & May, 2015). Renal medullary hypoxia can lead to mitochondrial dysfunction, initiating a progressive loss of renal function culminating in AKI (Lankadeva, Okazaki, Evans, Bellomo & May, 2019; Nourbakhsh & Singh, 2014). Therapies that target these sepsis-induced pathophysiological processes may confer better circulatory management and mitigate AKI.