Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism.

It may be located in any part of the body, but most commonly in the lungs, brain, urinary tract, skin or abdominal organs.

It most commonly affects children, immunocompromised individuals, and the elderly, as their immune systems cannot deal with infection as effectively as those of healthy adults.

The precipitating infections that may lead to septic shock if severe enough include but are not limited to appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, necrotizing fasciitis, MRSA and mesenteric ischemia.

[7] The pathophysiology of septic shock is not entirely understood, but it is known that a key role in the development of severe sepsis is played by an immune and coagulation response to an infection.

[9] Toxins produced by pathogens cause an immune response; in gram-negative bacteria these are endotoxins, which are bacterial membrane lipopolysaccharides (LPS).

Type II, membrane-damaging toxins, destroy cell membranes in order to enter and include hemolysins and phospholipases.

[citation needed] In gram-negative sepsis, free LPS attaches to a circulating LPS-binding protein, and the complex then binds to the CD14 receptor on monocytes, macrophages, and neutrophils.

This signaling results in the activation of nuclear factor kappaB (NF-κB), which leads to transcription of a number of genes that trigger a proinflammatory response.

TLR-mediated activation helps to trigger the innate immune system to efficiently eradicate invading microbes, but the cytokines they produce also act on endothelial cells.

[citation needed] In response to inflammation, a compensatory reaction of production of anti-inflammatory substances such as IL-4, IL-10 antagonists, IL-1 receptor, and cortisol occurs.

Pathogenic bacteria may employ LPS with low biological activity to evade proper recognition by the TLR4/MD-2 system, dampening the host immune response and increasing the risk of bacterial dissemination.

Yet, defining and understanding how even the smallest structural differences between the very similar LPS species may affect the activation of the immune response may provide the mechanism for the fine tuning of the latter and new insights to immunomodulatory processes.

[14] Septic shock may be defined as sepsis-induced low blood pressure that persists despite treatment with intravenous fluids.

Cytokines released in a large scale inflammatory response result in massive vasodilation, increased capillary permeability, decreased systemic vascular resistance, and low blood pressure.

Prompt antimicrobial therapy is important, as risk of dying increases by approximately 10% for every hour of delay in receiving antibiotics.

[10] In 2017, the FDA approved angiotensin II injection for intravenous infusion to increase blood pressure in adults with septic or other distributive shock.

[31] Tentative evidence exists that Polymyxin B-immobilized fiber column hemoperfusion may be beneficial in treatment of septic shock.

[33] Recombinant activated protein C (drotrecogin alpha) in a 2011 Cochrane review was found not to decrease mortality and to increase bleeding, and thus, was not recommended for use.

Sepsis has a worldwide incidence of more than 20 million cases a year, with mortality due to septic shock reaching up to 50 percent even in industrialized countries.