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.