Septic shock - pathophysiology and symptoms

- Septic shock is a very serious condition. About half the patients who have septic shock will die within the first month of their diagnosis. But what is septic shock? Let's break down the two words. Septic comes from the old Latin term meaning "rotten", and the word shock, of course, means decreased tissue oxygenation and low blood pressure. So combined, it's decreased tissue oxygenation caused by something that is rotten. Now, this rotten thing is an infection, infective material, that causes some sort of inflammation. So it's infective material that causes decreased oxygenation of tissues. So how does infective material do that? Let's take a look at a blood vessel and of course the blood is used to deliver oxygen to tissue. So here's some red blood cells, and I'll put some tissues right here. These little boxes represent cells. So these red blood cells are supposed to transfer oxygen, this little purple substance right here, to these cells. Delivery of oxygen to the tissues. Now let's say there's some sort of infective material in the bloodstream. White blood cells will encounter this infective material whether it's bacteria, virus, or a fungal infection, that's in the bloodstream. So now your blood vessels are like pipes, septic pipes, containing this sewage, this unclean material. It's no longer sterile. So this white blood cells, their job is to find this and clean it up. Of course when white blood cells encounter this infective material, they activate. When they activate, there are several things these white blood cells do. First, they're going to call on other white blood cells to come and check this out, because the idea is you want to recruit as many white blood cells to wherever this infective material is so you can eradicate it. So first, white blood cells recruit their buddies. Now here comes a major point. This infective material is normally not in the bloodstream, in fact, it's usually out here in the interstitial tissue. So usually white blood cells have to get into the interstitial tissue and eliminate the threat. White blood cells do that by releasing molecules, such as nitrous oxide. The molecules that are released interact with the blood vessels, and cause the blood vessels to do a couple things. First of all, blood vessels will dilate. Or in other words, the diameter of the blood vessel will increase in size. So let me go ahead and erase some of this so we can show the dilation of the blood vessel. So let's make this dotted, showing that it was this size, and now, blood vessel diameter increases. We've increased from this size to a little bit larger. This causes a localized decrease in vascular resistance, systemic vascular resistance. The blood, all of the blood contents, have more space to move around, and there's less resistance that they're bumping up against, because of this widened diameter of the blood vessel. So there's increased diameter of the vascular space. Of course, this makes sense if this is happening locally, blood slows down in an area where there is an infection. Because remember, the immune system usually encounters infective material in the peripheral tissues. To be able to get into the peripheral tissues, white blood cells need to make the blood vessels leaky. So that's the second thing that's happening here. Increase diameter and increase permeability, or leakiness, of the blood vessels. Here is actually the cause of shock. You have this infective material in the blood vessels all throughout the body, so this happens everywhere, systemic vascular dilation, or vasodilation. This decrease in vascular resistance causes a drop in blood pressure, because remember, vascular resistance and cardiac output equals blood pressure. A large drop in this causes a large decrease in pressure. But also they have low tissue perfusion, because the equation for tissue perfusion is really the same, cardiac output and systemic vascular resistance contribute to tissue perfusion. But let me show you something else that's causing low oxygenation of the tissues, low tissue perfusion. You've got these cells that are receiving oxygen from red blood cells. With the increased leakiness, fluid will get into the tissues. So you have all this fluid buildup in the tissues, and this makes it really difficult for oxygen to get to the cells it needs to. It has to diffuse through all this fluid. These cells become starved of oxygen. This is primarily what causes shock. There's a third thing that happens when these white blood cells encounter this infective material. They want to destroy it, right? If you've got bacteria, or a virus, or fungus, that's the job of the white blood cells, to destroy this infective material. These white blood cells release lytic enzymes and reactive oxygen species that cause damage to destroy this pathogen, but again, this is happening everywhere. So not only do you damage the pathogens, but you'll end up damaging the blood vessels as well. So that's number three. You have damage of blood vessels. Remember, this is happening everywhere, and because of that, serious complications can occur. First of all, when blood vessels get damaged, there are things called coagulation factors in the blood. I'm gonna make them this little lavender color. They're a protein that helps cause clotting, so when blood vessels get ruptured, you want to create a clot to patch this up, so that blood doesn't spill into the extravascular space outside of the blood vessel. Again, this is happening to blood vessels everywhere in the body, I cannot emphasize that enough. So what ends up happening is these coagulation factors end up getting used up. They're trying to patch up all these blood vessels, so clots are forming everywhere. Some of these clots actually break off into the bloodstream, so an interesting thing happens. There's coagulation that's happening in the vascular system, but the coagulation can't keep up with the breakage of blood vessels. So sooner or later, blood is spilling out of the blood vessels. This weird state of coagulation in the blood vessels with simultaneous bleeding is called disseminated intravascular coagulation. Coagulation in the intravascular space, inside the blood vessels, and it's everywhere. It's disseminated everywhere. This is a very serious complication that can be seen in septic shock. Another complication that can be seen in septic shock is ARDS, acute respiratory distress syndrome. As you know, the lungs are highly vascularized, they have a lot of blood vessels, because they need to be able to take oxygen from the atmosphere to saturate blood vessels. Let's, again, return to our pathology of septic shock. This is happening everywhere, and the damaging enzymes and cytokines and different immune molecules end up damaging blood vessels in the lungs as well. If you damage all of these blood vessels in the lungs, then oxygen won't be absorbed properly into the bloodstream. So patients with severe septic shock end up in respiratory distress, because they can no longer pull in oxygen from the environment into their bloodstream. So that's acute respiratory distress syndrome. A final point that I want to touch on is the cardiac output. Cardiac output will initially increase to try to compensate for this decreased vascular resistance, right? It makes sense that if you increase cardiac output, it will even out the blood pressure. However, as septic shock goes on, the heart, too, can become paralyzed and damaged by all these molecules, these immune molecules. If left untreated long enough, cardiac output will start to be depressed. Cardiac output will decrease. Of course, if you decrease cardiac output instead, then blood pressure will also decrease. For symptoms, think about a very severe infection. With a severe infection, you'll see things such as fever, chills, and sweating. But a major symptom of septic shock is warm skin. As these blood vessels dilate in size, as they increase in size, this happens in all organs, and the largest organ in your body is technically the skin. So the skin takes out a lot of the blood from the rest of the body. So initially, patients will have very warm skin. However, as a patient is in shock long enough, and their sympathetic nervous system tries to increase blood pressure, it's going to clamp these vessels back down to try to improve the resistance, the systemic vascular resistance, and maintain blood pressure. With progression of septic shock, patients will eventually have cooler skin, and this is a bad sign, because, obviously, it means septic shock has been occurring for a long period of time. And the clamping down of these blood vessels doesn't necessarily mean that fluid can't escape anymore, the blood vessels are still going to be leaky from all these vasoactive molecules that are increasing the leakiness and permeability of the blood vessel. So you'll still have this decreased tissue perfusion from all of this fluid that's accumulating in the tissues. Also, you'll see other symptoms such as respiratory distress, altered mental status, and decreased urination. As organs get starved from oxygen, they start to lose the functions they normally carry out.