Pathophysiology   Pathogen recognition by immune cells – e.g. LPS-LBP endotoxin recognised by macrophages – leads to release of inflammatory mediators including TNFα, IL-1, and IL-6. This becomes generalised and eventually results in widespread cytokine activation. Cytokines and inflammatory mediators lead to vasodilation, causing a distributive shock. Microcirculatory failure and tissue hypoperfusion results from (a) inflammatory endothelial dysfunction and (b) an imbalance of coagulative and fibrinolytic mechanisms causing microvascular thrombosis, which may generalise to DIC. Positive blood cultures support the diagnosis but are not required, and are only found in 1/3.  Staph. aureus ,  Strep. pneumo , and Gram negative bacilli are the commonest pathogens. Definitions Sepsis-2 criteria Systemic inflammatory response syndrome (SIRS) is ≥2 of the following: Temperature outside the range of 36-38°C. WBC outside the range of 4-12. HR >90 RR >...