What is Sepsis Anyway?

Don’t feel bad if you don’t have a really good answer. Most of us don’t. Before I started researching the question two years ago, I didn’t have much of an answer either. People get sick. Some get better. Some get worse. If they get really sick they transition into septic shock. End of story.

As an EMS educator, I didn’t go into too much more detail than that, so my own lack of knowledge was carried forward by my EMT students and the cycle continued. Sure, I could turn around and blame my instructor, but here’s a better idea, let’s end the cycle right now.

Here is your one stop shopping guide to the pathophysiology of sepsis. Give me a few minutes of your time and I’ll give you a more complete understanding of the etiology that we call sepsis than most of the prehospital folks you’re working alongside. Put your thinking cap on. Here is sepsis in a nutshell.

The Sepsis Progression

1) The Source of Infection

It all begins with an exogenous pathogen. There’s got to be one. Some outside bad thing, be it viral, bacterial, fungal or parasitic, finds its way into our bodies and takes up residence. And more often than not, you can identify it. Either by digging in for more information about the presenting symptoms or asking questions about high risk possibilities.

The source of infection could be a wound, a recent surgical procedure or an exposure to someone with a known infection. Or it could be an exacerbation of any of the run of the mill infection that we humans commonly get. From pneumonia to bladder infections, any common infection can advance from a localized minor complaint to a systemic inflammatory response.

2) Pro and Anti-Inflammatory Mediators in Balance

In response to that pathogen, our bodies wage a complex war against the outside invaders. Pro-inflammatory mediators like braykin, C3 and C5 from the component system and histamine cause local tissue inflammation. This causes damage to the endothelial walls of the vasculature. Vessels leak fluid into the intercellular space.

At this stage, it’s important to keep in mind that all of this is actually a good thing. Leaky vessels help to spread erythrocytes to the source of infection. Inflammation is the first stage of tissue healing. All is right with the inner world.

3) The Pro-Inflammatory Surge

This is where things start to go awry. Here at the tipping point between uncomplicated infection and sepsis, the balance between pro-inflammatory and anti-inflammatory mediators shifts. Anti-inflammatory mediators become overwhelmed The body begins producing more pro-inflammatory mediators and the ones already in circulation overstay there welcome.

At this point, what was a localized inflammatory attack becomes a full, system-wide inflammation party. All of those things that are helpful at a local level become problematic when pro-inflammatory mediators increase at an unchecked rate. The result is known as SIRS. (Systemic Inflammatory Response Syndrome.)

4) Endothelial Damage and Impaired Fibrinolysis (Vessels Leak and Blood Clots)

With unmediated inflammation running the show, a bunch of bad stuff happens. The top two problems on the list are endothelial damage and impaired fibrinolysis.

  • Endothelial Damage – Recall that those pro-inflammatory mediators weren’t very gentle with the vessel walls. They roll along tearing up the cells lining the vessel wall and allowing fluid to leak from the vessel. As this happens system-wide, large volumes of vascular fluid leaks into the intercellular space. This leads to a distributive shock state. Without enough circulating blood volume the body transitions into a state of shock.
  • Impaired Fibrinolysis – Chemical imbalances initiated by the pro-inflammatory surge disrupt the normal clotting cascade. This causes the blood remaining in the vasculature to clot. Blood clots clog the micro-vasculature necessary to deliver oxygen to vital organs. Systemic clotting is the second punch in the one-two combination of septic shock.

5) End Organ Hypoxia and Failure

The deadly combination of big blood vessels leaking and small blood vessels clotting combine to cut off the oxygen supply to every organ in the body. This end organ hypoxia effects every major system in the body. Liver and kidneys fail, lungs lose function, cardiac muscle weakens, blood vessels dilate, and even basic functions like digestion and temperature regulation ultimately fail. This phase is sometimes referred to as MODS or multiple organ dysfunction syndrome.

These signs of end organ failure are what we typically associate with septic shock. The real challenge in sepsis is identifying the septic progression before it reaches the severe sepsis phase. Once system wide inflammation, vessel leakage and clotting are underway, mortality rates can exceed fifty percent. Much like hypovolemic shock, time is a critical factor in saving lives.

While EMS is accustomed to racing off to trauma centers with patients who are at risk for hypovolemia, our response to sepsis presentations are often a bit more hum-drum. Hopefully, with your new understanding of the sepsis progression, you’ll be more prepared to identify your next septic patient and respond.


  1. So of the S/S of fever (or hypothermia), tachycardia, tachypnia, and AMS what else should I be looking for as I’m forming my general impression and the possibilities are racing through my mind? What should put sepsis HIGHER on my list?

    I guess really as a basic, shock is shock, and when I see it there is only so much I can do.

  2. So of the S/S of fever (or hypothermia), tachycardia, tachypnia, and AMS what else should I be looking for as I’m forming my general impression and the possibilities are racing through my mind? What should put sepsis HIGHER on my list?

    I guess really as a basic, shock is shock, and when I see it there is only so much I can do.

  3. Sean Fontaine says:

    Basics, like medics have the potential to recognize and begin treatment of a septic pt. One thing my time on transfer cars taught me was most SNF pts are septic and undertreated due to a lack of education of the staff. Any SNF pt w/a leg bag filled w/brown urine is @ some level of sepsis.
    Our current Sepsis alert protocol was instituted because we (pre and hospital) were always undertreating our septic pts and as such their outcomes were poor. Now we look @ BP (mean arterial pressure), S/Sx (hyper/hypothermia), tachy/bradycardia, tachypnea, skin conditions, known/possible Hx of infection, possibly AMS. Basically, a pt w/possible/known infection (SNF pts, diabetics, recent surgery pts, very sedentary people, etc) and SIRS. What we do now is a large fluid bolus and alert the hospital that they may be septic, they then continue w/the fluid bolus, rapid ABX, and run blood diagnostics to confirm treatment is correct.
    Gary, you’re right shock is shock, in the absence of CHF exacerbation these pts need a lot of fluids because their fluids aren’t in the proper space, so they’re hypovolemic. So, as a basic use your assessment skills, your further research of sepsis (implying you should do more than this post), and experience (how much you have) guide you. When in doubt as a basic, start conservatively w/fluids and inform the receiving hospital why you believe they are septic. The one certainty I’ve seen is if they are blown off and they’re septic, they will die.
    Am I way off on this Steve?
    Am I way off base here, Steve.

  4. Sean Fontaine says:

    Apparently typing when exhausted I can’t proof read.

  5. Dude,
    I just want to say I have just found your site and I am loving it.
    Very enlightening. This piece has made me realise we under treat and aren’t recognising sepsis.
    I am a Paramedic in England. Incidentally.
    I shall continue to read in future.


  6. ^ Same.

    Also, in most of These United States, Basics can’t give fluids. Doesn’t mean we shouldn’t understand what we’re treating for, though.

  7. Look at a survival of sepsis from a patient’s perspective in my new book Gyroscope, A Survival of Sepsis.

    Best regards,

    Gary Black, author and survivor

  8. See more about sepsis. See reviews of Gryoscope: A Survival of Sepsis being used by several doctors when they speak at conferences about Sepsis, and critical care response.