Systemic inflammatory response syndrome develops from systemic spillover of what often starts as a localised inflammatory and coagulation response to a known inflammatory stimulus. Aetiology can be infectious or non-infectious (see figure 1 below).
Infectious causes can include infection caused by bacteria, viruses and yeasts and includes:
- Bowel perforation/Peritonitis
- Abdominal Abscess
- Urinary Tract Infection
- Soft Tissue Infections
- Catheter-related or Medical device related
Non-infectious causes of SIRS can include:
- Cardiopulmonary bypass
- Massive transfusion.
Figure 1: Causes of SIRS and Sepsis
Hospital acquired infections are often associated with resistant organisms, including MRSA. A good knowledge of local infection patterns is vital and it is important that the microbiology department are involved at an early stage.
Gram positive cocci and gram negative bacilli are the most commonly implicated in the pathogenesis of sepsis; components of the bacterial cell wall may trigger the inflammatory process as shown in below in figure 2.
Figure 2: Pathophysiology of Sepsis
Bacterial components bind to a receptor called CD14 on the surface of monocytes. Toll-like receptors (TLR), also found on monocytes are involved and have specific affinity for certain microorganisms. 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 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). The activation and amplification of these cascades leads to the clinical features of the syndrome we recognise as sepsis:
NO induced vasodilatation leads to hypotension and poor perfusion, disruption of the capillary endothelium leads to generalised oedema and hypovolaemia. This combined with activation of the coagulation system leads to poor microcirculatory flow and failure of oxygen delivery. It is also likely that in established sepsis tissue oxygen utilisation is impaired by enzyme mediated inhibition at mitochondrial level.
Untreated, this cycle of inflammation, coagulation, poor perfusion and impaired oxygen utilization leads to multiple organ failure and ultimately death.