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What is sepsis?

A video defining sepsis and the importance of understanding this definition.
Hello. My name is Helen Pardoe and I’m a consultant colorectal surgeon. Welcome to this section of the course covering the question, what is sepsis?
What is sepsis and why is it important that we understand what it is? Sepsis is not a new condition. Its name goes back to the time of Hippocrates. The definition today is the current definition as agreed by the Third International Consensus. And the reference associated with this is the 2016 February edition of the Journal of the American Medical Association. Part of the difficulty is that the definition of sepsis keeps changing. And understanding of the biochemical mechanisms of sepsis continue to evolve. For experienced learners, the definition on this course is probably different from what you learned a few years ago. And for those new to learning about sepsis, I’m afraid the definition will change within your working life.
However, the fundamental cause is an infection in the body. The damage is how the body deals with the infection. But remember, infection can be a bacteria, virus, or a fungal infection. However antibiotics are only of benefit in bacterial infections.
The start of sepsis is when a microorganism attacks the body. The key is that the body has to recognise the invader and respond to it such that the pathogen and its effects do not overwhelm the person. So what are the ways for the body to recognise a microorganism? PAMPs, or Pathogen Associated Molecular Patterns are molecules which are specific to microorganisms. They’re not associated with human cells - allowing the body’s defence cells to recognise the microorganism and respond. Examples of PAMPs are the lipopolysaccharide of the cell wall of gram negative bacteria and single stranded viral DNA. DAMPs, in contrast, are molecular patterns from our own human tissue but they’re only released from a cell when it is damaged.
And examples of these are heat shock proteins, ATP, and host DNA. Both of these bind to pattern recognition receptors, which are found on the defence cells. Endothelial cells, macrophages, lymphocytes, mucosal epithelial cells, for example. Binding of these molecular patterns will stimulate the immune response.
Interleukin-1 and 2, TNF-alpha are examples of cytokines: low molecular weight proteins involved in the immune response. They are produced by all cells involved in immunity, but especially T cells. And their release activates both the innate immune response and the adaptive response. When there’s a large number of bacteria, the activation of the innate immune response is extreme. Cytokine release becomes excessive. Neutrophils release damaging proteases and toxic oxygen radicals. And these start to attack not only the pathogen but also the host. Hence, the response becomes dysregulated and sepsis becomes established.
This cascade of immunity is the underlying mechanism for the clinical signs of sepsis. Damage endothelium leads to hypotension and hypovolemia. And we see acute kidney injury and confusion associated with hypotension and hypoxia. There’s an associated cardiovascular response and deterioration in function. Cytokines activate the clotting cascade causing microthrombi which, through depletion of clotting factors, can lead to haemorrhage. In the emergency department of the hospital or in the wards, clinical staff are presented with an acutely unwell patient with dysfunction in multiple organ systems. The long term effects of a treatment of septic shock can be truly catastrophic.
In summary, sepsis is a serious life threatening condition which affects multiple organ systems through multiple pathways. Because of this, we can understand why there is such a challenge to identify a single biomarker for the diagnosis of sepsis. And no single treatment modality is likely to be successful.

In this video, Helen Pardoe discusses the definition of sepsis and why it is important that we understand what sepsis is.

Part of the difficulty is that the definition of sepsis keeps changing and the understanding of the biochemical mechanisms of sepsis continue to evolve. This video states what sepsis is defined as currently. How the body recognises and responds to infection is covered, as well as the clinical manifestation of sepsis.

References cited in the video have been provided as direct links in the see also section below.

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Procalcitonin: PCT as a Biomarker for Antimicrobial Stewardship

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