Bacterial components bind to a receptor called CD14 on the surface of monocytes. Other important components include:

• Toll-likereceptors (TLR)

TLR are proteins found on macrophages, neutrophils and other cells in the immune system. They allow the recognition of molecules specific to micro-organisms (such as lipopolysaccharide), which can then be distinguished from host cells.  

Activation of these receptors in turn trigger transcription factors such as Nuclear Factor Kappa Beta (NFkB) resulting in secretion of a variety of pro and anti-inflammatory mediators.

• Inflammatory mediators

Inflammatory mediators include interleukins 1, 2 and 6 (IL-1, IL-2, IL-6) and Tumour Necrosis Factor Alpha (TNFa).

These substances in turn lead to activation of leukocytes, endothelial damage, activation of the coagulation cascade and increased synthesis of nitric oxide (NO).

• Nitric oxide (NO)

In sepsis, excessive NO is produced. NO produces vasodilatation leading to hypotension and poor perfusion.

Disruption of the capillary endothelium leads to generalised oedema and hypovolaemia.

Activation of the coagulation system, to which NO contributes, contributes to poor microcirculatory flow and failure of oxygen delivery.

In established sepsis, tissue oxygen utilisation is impaired by enzyme mediated inhibition at mitochondrial level.

Untreated, a cycle of inflammation, coagulation, poor perfusion and impaired oxygen utilisation leads to multiple organ failure and ultimately death.