Sepsis is one of those words that strikes fear into the heart of every nurse and can often be perceived as a death sentence, but what’s really going on?

Who’s the culprit?

The underlying cause of sepsis can be any old bog-standard infection; this could be a bacterium, virus, fungi or protozoa. Once there is some source of infection, the immune system goes about it’s normal business kicking pathogen butt, however this is where things go wrong.

Who’s at risk?

Like most illnesses, it’s very young children and older patients, particularly those with other underlying comorbidities that are at the most risk. Urinary tract infections and intra-abdominal infections with a gram-negative-bacteria is the most common sepsis causing culprits, with E. coli being the most popular offender (Kang et al., 2011). Patients with impaired immune systems (eg chemotherapy or high dose steroids), those who have had recent surgery, drug misusers, anyone with lines in situ (eg central or IV lines and urinary catheters) or pregnant women are just some of the more at risk groups (NICE, 2017).

Role of the immune system

At the heart of sepsis sits the immune system. Sepsis itself is characterised as “dysregulated host response to infection” which leads to organ damage (Singer et al., 2016). Here is a very abbreviated series of events:

  1. Infection – pathogenic organism stimulates the immune system.
  2. Immune reaction – the immune system gets all excited about the invading pathogen and begins to attack it as described in any A&P textbook every written.
  3. Overstimulation – the immune system continues to release even more immune mediators like cytokines to stimulate more immune cells, which themselves release extra cytokines and reactive oxygen species.
  4. Damage to self – while the immune system is amazing at killing off pathogenic organisms, it can also damage the self in the process, things like the reactive oxygen species mentioned above don’t discriminate between self and non-self. This damage further winds up the immune system (Rittirsch, Flierl and Ward, 2008).
  5. Immunosuppression – following the initial overstimulation of the immune system, the protective mechanisms that are also an integral part of the immune system are activated. At the same time as immune cells such as neutrophils and macrophages are releasing pro-inflammatory cytokines, they are also releasing anti-inflammatory ones to help moderate the damage they’re causing to the self (Boomer et al., 2011). Immune cells apart from macrophages, neutrophils and regulatory T-cells begin to undergo apoptosis (Hotchkiss et al., 2002; Tamayo et al., 2012; Hotchkiss, Monneret and Payen, 2013).
  6. Impaired immune function – the rapid decline in the number of immune cells leads to impaired immunity, leaving the person open to further infection (Stephan et al., 2002).


The role of the immune system is just one part of the pathophysiology:

Coagulation – dysregulation of proteins related to coagulation can lead to disseminated intravascular coagulation in severe sepsis cases and the formation of thrombi (Levi and van der Poll, 2010). The immune overreaction also decreases production of factors related to anticoagulation (Angus and van der Poll, 2013).

Endothelial barrier dysfunction – the endothelium is a barrier that coats the inside of vascular vessels and during sepsis its function becomes compromised. The ‘skeleton’ of the endothelial cells (a molecule named actin) and the junctions between these cells are altered by platelets, neutrophils and other immune mediators; this barrier then becomes ‘leaky’ and proteins and plasma fluids escape into the extravascular spaces (Hotchkiss et al., 2016).

Hypotension – excess release of prostaglandins and other immune mediators aimed at increasing immune cell infiltration lead to vasodilation (Angus and van der Poll, 2013). This is further compounded by the endothelial barrier dysfunction above; this dysfunction is the reason IV fluid challenges don’t always work, with the extra fluid just passing straight out of the vascular system, causing oedema (Hotchkiss et al., 2016).

Respiratory stuff – another area of the body that gets hit in the immune system crossfire is that of the alveoli, where inflammatory mediators damage the capillary membranes, decreasing gas exchange, with the patient presenting as tachypnoeic and having abnormal blood gases (Hotchkiss et al., 2016).

Organ dysfunction – this is essentially the end point where all of the bits I’ve written about above collaborate and lead to a sever breakdown in homeostasis (Angus and van der Poll, 2013). Persistent hypotension leads to poor organ perfusion, inflammatory cells and reactive oxygen species damage cells and mitochondria, decreasing energy production and gaseous exchange is compromised.

So what?

One of the biggest barrier in the treatment of sepsis is recognition of the condition in the first place, particularly as one third of patients who present to ED will have vague symptoms that aren’t always congruent with infection. In these cases, patients often do not receive antibiotics as quickly and therefore are twice as likely to die (Filbin et al., 2018). Unfortunately, there is no single definitive test for sepsis as it comprises so many different symptoms and includes every organ system. Utilising assessment tools such as the National Early Warning Score (NEWS) can help identify patients at risk of sepsis early on, with NEWS having its own triggering system. Further guidelines such as the Sepsis 6 or BUFALO can then be used to aid doctors in their diagnosis and treatment.

The reality is that early recognition means earlier treatment. If at any point a patient does trigger a sepsis warning on their observations or even if they’re not and something just isn’t right, bring it up with the appropriate doctor (or call 111/999 if in the community etc) and follow your local policy. An altered mental state or raised respiratory rate can be the first signs of infection (and many other things) and these should always be escalated.

It’s also vital that the patient is supported during this time (along with their family etc) as the whole picture becomes medical very quickly, with IV fluids, blood cultures and antibiotics often becoming a priority over the patient as a person. The word sepsis itself can be very distressing, particularly due to increased awareness of the condition and pervasiveness in the media with certain high-profile cases. Not forgetting things such as pain relief in amongst all of the doctor-y bits can just help make a patient more comfortable along with reassurance

More info:

Different Trusts will also have their own sepsis champions, and I know one of my local ones has a sepsis speciality nurse – get in contact and spend some time with them.


Angus, D. C. and van der Poll, T. (2013) ‘Severe Sepsis and Septic Shock’, New England Journal of Medicine, 369(9), pp. 840–851. doi: 10.1056/NEJMra1208623.

Boomer, J. S. et al. (2011) ‘Immunosuppression in patients who die of sepsis and multiple organ failure.’, JAMA, 306(23), pp. 2594–605. doi: 10.1001/jama.2011.1829.

Filbin, M. R. et al. (2018) ‘Presenting Symptoms Independently Predict Mortality in Septic Shock’, Critical Care Medicine, 46(10), pp. 1592–1599. doi: 10.1097/CCM.0000000000003260.

Hotchkiss, R. S. et al. (2002) ‘Depletion of Dendritic Cells, But Not Macrophages, in Patients with Sepsis’, The Journal of Immunology, 168(5), pp. 2493–2500. doi: 10.4049/jimmunol.168.5.2493.

Hotchkiss, R. S. et al. (2016) ‘Sepsis and septic shock’, Nature Reviews Disease Primers, 2, p. 16045. doi: 10.1038/nrdp.2016.45.

Hotchkiss, R. S., Monneret, G. and Payen, D. (2013) ‘Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy.’, Nature reviews. Immunology, 13(12), pp. 862–74. doi: 10.1038/nri3552.

Kang, C.-I. et al. (2011) ‘Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.’, The Journal of infection, 62(1), pp. 26–33. doi: 10.1016/j.jinf.2010.10.010.

Levi, M. and van der Poll, T. (2010) ‘Inflammation and coagulation’, Critical Care Medicine, 38(2 Suppl), pp. S26–S34. doi: 10.1097/CCM.0b013e3181c98d21.

NICE (2017) Sepsis: recognition, diagnosis and early management. NICE. Available at: (Accessed: 10 March 2019).

Rittirsch, D., Flierl, M. A. and Ward, P. A. (2008) ‘Harmful molecular mechanisms in sepsis.’, Nature reviews. Immunology, 8(10), pp. 776–87. doi: 10.1038/nri2402.

Singer, M. et al. (2016) ‘The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)’, JAMA, 315(8), p. 801. doi: 10.1001/jama.2016.0287.

Stephan, F. et al. (2002) ‘Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients.’, Critical care medicine, 30(2), pp. 315–22. Available at: (Accessed: 17 February 2015).

Tamayo, E. et al. (2012) ‘Evolution of neutrophil apoptosis in septic shock survivors and nonsurvivors.’, Journal of critical care, 27(4), p. 415.e1-11. doi: 10.1016/j.jcrc.2011.09.001.

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