Author: Tanner Marshall, MS
Editor: Rishi Desai, MD, MPH, Tanner Marshall, MS
So when we talk about ischemia, we’re usually talking about this lack of blood flow to a specific area of tissue, so maybe like with a heart attack, a coronary artery in the heart gets blocked that supplies the left ventricle with blood...so that localized area of heart tissue doesn’t get enough blood and oxygen and that damage is localized to that left ventricle. Shock is like ischemia...but on a global scale, in other words it’s a whole body circulatory failure, where blood flow to tissues is dangerously low, leading to cellular injury, possibly damaging multiple organs and even leading to multiple organ failure if not treated immediately.
Ok, so with shock, the body’s tissues aren’t getting enough oxygen via the blood, right? Normally, blood perfuses through tissue and delivers oxygen because there’s enough pressure in the circulatory system to push it through; so blood pressure’s a major determinant for the amount of blood perfusing through tissues.
Now blood pressure’s determined by two components, the resistance to blood flow in the blood vessels, things like vessel length, blood viscosity, and vessel diameter, and the cardiac output which is the volume of blood pumped by the heart through the body per minute. And you can break that into heart rate, the number of beats per minute, times stroke volume, the amount pumped out each beat. Going even further, the stroke volume is found by taking the total volume of blood left over after contraction, the end-systolic volume, and subtracting it from the total volume in the heart after filling, the end-diastolic volume.
Alright, now keeping all those in mind, shock can be caused by whole bunch of different things, but we can categorize the different types of shock into the three main categories, along with some subcategories here and there. The first category is called hypovolemic shock. Hypo- means “low”, -vol- refers to “volume”, and -emia refers to the blood, so hypovolemic shock is shock induced by a low fluid volume of blood, and this could be either non-hemorrhagic or haemorrhagic. Non-hemorrhagic means that the loss of fluid volume isn’t from bleeding, so this could be like if you were stranded in a desert and suffered severe dehydration, eventually your loss of fluid in sweat would reduce blood volume to where it wouldn’t be enough to supply your body’s organs and you’d develop hypovolemic shock. Hemorrhagic hypovolemic shock on the other hand is loss of blood volume through ruptured blood vessels, in other words, from bleeding. A loss of about 20% of your total blood volume, roughly one liter, can be enough to induce hypovolemic shock,
and when that L of blood leaves the circulation, the total volume filling into the heart goes down, meaning the end-diastolic volume goes down, this means stroke volume goes down as well, which causes cardiac output to go down, and finally we see blood pressure goes down. When cardiac output goes down, catecholamines like epinephrine and norepinephrine, ADH, and angiotensin II are released, all of which cause vasoconstriction of blood vessels which increases of vascular resistance, and increased heart rate, which, increases cardiac output, and these combined effects increase blood pressure.
A super important indicator of tissues not getting enough oxygen due to hypovolemia, is a decreased mixed venous oxygen saturation, or MVO2. MVO2 is the amount of oxygen bound to to hemoglobin in blood coming to the right side of the heart, from the tissues. So it’s like the amount of oxygen left over, or not extracted and used by the tissues. So if blood volume’s down, that means oxygen’s down, and there’s going to be less left over, right? So MVO2 will be down with hypovolemic shock.
Since blood flow provides heat to the tissues as well, when it’s down, the skin starts to feel cool and clammy; and so hypovolemic shock is considered a cold shock.
A second main category of shock is cardiogenic shock, cardio - genic means produced by the heart, right? So this is when something happens to the heart such that now it can’t pump enough blood to the body’s tissues. The most common cause is acute myocardial infarction, or heart attack. Hold on a second, though...didn’t I say at the beginning that was more along the lines of localized ischemia? Well, the heart attack itself reflects ischemia, right? But the effects of the initial cardiac damage eventually leads to a state of shock.
When the heart’s muscle cells die, it can’t contract as hard, which means the amount of blood pumped out, or stroke volume, goes down, and therefore cardiac output goes down as well. In the same way as with hypovolemic shock, the body releases vasoconstrictors to increase vascular resistance and help maintain blood pressure.
Also, as with hypovolemic shock, MVO2 will be down since there’s less oxygen being pumped out, and so less will be left over. Sometimes there might be an obstruction that doesn’t allow the heart to fill properly with blood. For example, we might have the pericardial sac fill up with fluid from an infection or blood from a traumatic accident like getting stabbed in the chest.
If this sac fills up, it physically constricts the heart from expanding and contracting normally and also reduces the stroke volume. This is sometimes “sub” classified as obstructive shock, but you can see that the cause is still due to the heart’s inability to do its job, right?
Similarly to hypovolemic shock, a reduction in cardiac output leads to lowered blood flow, so the skin gets cool and clammy and so cardiogenic shock is also considered a kind of cold shock.
Alright, the third main category of shock is called distributive shock, where there’s typically “leakiness” of blood vessels and an excessive amount of arteriole vasodilation, or widening of the peripheral blood vessels, which remember is one of the components of vascular resistance. If arterioles dilate, vascular resistance to blood flow goes down and blood pressure goes down, leading to less perfusion and distribution of blood to organs and tissues.
Now the most common type of distributive shock is septic shock, from pathogens in the blood, most commonly gram-negative pathogens.
What happens with septic shock, is endotoxins, these large clunky lipopolysaccharide molecules (sometimes just called LPS) found on the outer membrane of gram-negative bacteria causes a crazy cascade of events that ultimately leads to lowered perfusion.
First these guys directly damage endothelial cells and cause them to release vasodilators like nitric oxide. They also activate the complement pathway in the blood, which stimulates mast cell release of histamine, another vasodilator. The LPS molecules also activate immune cells like macrophages and neutrophils, which help create a bunch of pro-inflammatory cytokines like tumor necrosis factor and interleukin 1. These help the immune system destroy the invaders...but they also stimulate the endothelial cells to release more inflammatory molecules like platelet activating factor and reactive oxygen species. All of these inflammatory chemicals damage the endothelial cells and increases their vascular permeability, making the blood vessels “leaky”.
Also, endothelial cells express a procoagulant called tissue factor, procoagulants are molecules that increase blood coagulation, or blood clotting; and this, in combination with an overall decrease in anti-coagulants, which usually decrease clotting and seem to be often depleted or used up during sepsis, leads to this net increase in coagulation and clotting in the microvasculature, and of course clotting and blockages in the blood vessels further decreases perfusion, right?
Okay so this widespread vasodilation means very little vascular resistance, and blood can’t get the chance to unload as much oxygen as it cruises through the vasculature, and it gets back to the right side of the heart with leftover oxygen, so in this case, as opposed to cardiogenic and hypovolemic shock, MVO2 can be normal or even increased.
In contrast to hypovolemic and cardiogenic shock—now there’s an increase in flow in the peripheral blood vessels, and the skin becomes warm and flushed, so distributive shock is a kind of warm shock.
The overall combined effects of widespread vasodilation, increased vascular permeability, and microvascular blood clotting, all contribute to decreased perfusion of blood to vital organs.
Now two kind of sub-types of distributive shock are anaphylactic shock, which is an allergic reaction that causes dangerously low blood pressure, and neurogenic shock, where the nervous system gets damaged and can’t control the body’s blood pressure.