Pathogenesis of multi-organ system failure in sepsis

This is an attempt to reason though the cascade of linked events which leads to the catastrophic multi-organ collapse in severe septic shock.

Organ system failure

The systemic inflammatory response (which forms a part of the definition of sepsis) results in organ system dysfunction.

The diagram below is merely a simplified way of looking at the pathogenesis of something this complex. Imagine what it would look like if it elaborated on the specific cytokine pathways, metabolic derangements, etc.

septic shock cascade.

Lets try to reason through this.

Hypoxic respiratory failure

There is an increase in whole-body oxygen consumption, due to massive leucocyte activation as well as the increased metabolic rate of critical illness, as well as the increased metabolic rate associated with hyperthermia.

Not only that, but there may be a diffusion defect as the capillaries of the pulmonary circulation become leaky, and ARDS develops.

Hemodynamic collapse

The defining feature of septic shock, systemic vasodilation due to inflammatory mediators, results in decreased oxygen delivery to the whole body, exacerbating the dysfunction of the organs.

Septic cardiomyopathy

Thought to be due to impaired metabolite utilisation at a mitochondrial level, the cardiac dysfunction in sepsis results in biventricular failure.

Acute renal failure

As a result of decreased cardiac output, the renal function deteriorates, and oliguric renal failure becomes established. Not only that, but there is tubular dysfunction caused by the inflammatory cytokines, which is unrelated to the hypotension.

Hepatic dysfunction

Though the liver may not fail per se, there is typically a sepsis-associated rise in transaminases and bilirubin. Furthermore, the synthetic function is impaired, which contributes to the ensuing hypoalbuminaemia and coagulopathy.

Septic encephalopathy

Through mechanisms still poorly understood, severe sepsis results in a diffuse cerebral dysfunction which seems to worsen the prognosis. Cytokines, microvascular damage and impaired mitochondrial oxygen utilization have all been implicated.


Even in the absence of proper DIC, there is usually some degree of subclinical coagulopathy. There is simultaneously a depletion of coagulation factors and a decrease in their hepatic production.


An excellent resource for this topic are the chapters in Oh's Manual dealing with severe sepsis (ch 61, by A Raffaele de Gaudio) and with the immunocomrpomised host (ch 59, by Steve Wesselingh and Martyn A H French).

An older, yet similarly respectable source is Shoemaker (2005); Chapter 155 (Infections in the immunocompromised patient) by Andrew Githaiga, Magdaline Ndirangu and David L. Paterson covers this topic with great detail.