Sepsis is defined as an exaggerated, overwhelming and uncontrolled systemic inflammatory response to an initially localised infection or tissue injury, which may lead to severe sepsis and septic shock if left untreated (Daniels, 2009; Robson & Daniels, 2013; Dellinger et al, 2013; Perman, Goyal & Gaieski, 2012; Vanzant & Schmelzer, 2011). Septic shock can be classified by acute circulatory failure as a result of massive vasodilation, increased capillary permeability and decreased vascular resistance in the body, causing refractory hypotension despite adequate fluid resuscitation. This leads to irreversible tissue ischaemia, end organ failure and ultimately, death (McClelland & Moxon, 2014; ...view middle of the document...
He denies any nausea, vomiting or altered bowel/bladder habits. He also describes shortness of breath on exertion, on a background of feeling generally unwell by 3/7 days with decreased appetite, lethargy and diaphoresis. He denies any chest pain and has no pain on presentation.
Pathophysiology of Sepsis
Sepsis begins with a systemic inflammatory response to a perceived threat to the immune system (Powers & Burchell, 2010). Tissue injury or invading pathogens stimulate production of phagocytes, such as monocytes and macrophages, which act as the first line of defence against infection. These phagocytes release pro-inflammatory mediators called cytokines, in order to attract neutrophils to the site of infection. The release of cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNFα), results in release of further chemical agents, such as complement, histamine and prostaglandin. These agents cause localised vasodilation and release of cytotoxic chemicals, in an effort to destroy the invading pathogen. (Daniels, 2009) A rise in inflammatory markers (such as an elevated CRP) demonstrates this inflammatory response (due to release of IL-6).
In a certain sub-group of people with a host predisposition, such as those possessing a genetic variant of a receptor known as a ‘Toll-like receptor (TLR), activation of this inflammatory response results not only in damage to the localised endothelial lining, but also to overwhelming systemic vasculature damage (Daniels, 2009). At this point, the body attempts to regulate the innate inflammatory response by maintaining homeostasis through activation of the adaptive immune response. It does this by releasing anti-inflammatory cytokines, such as Interleukin-4 (IL-4) and Interleukin 10 (IL-10), to counteract the inflammatory response. However, due to progression of the inflammatory cascade, the homeostatic mechanisms of the body become overwhelmed and the body becomes unable to compensate for this excessive endothelial damage by IL-1 and TNFα. This mismatch of the host response to the pathogen contributes to haemodynamic instability (with or without hypotension), tissue injury and organ dysfunction.
This inflammatory process is evident is Mr Hertz’s raised serum CRP of 193, WCC of 13.5 and neutrophil count of 11.1 (see Appendix B). Also, his raised temperature of 37.7°C (see Appendix A) is indicative of...