- What is shock?
- Shock - hemodynamics
- Shock - oxygen delivery and metabolism
- Shock - diagnosis and treatment
- Cardiogenic shock
- Sepsis: Systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS)
- Septic shock - pathophysiology and symptoms
- Septic shock: Diagnosis and treatment
- Hypovolemic shock
- Neurogenic shock
- Obstructive shock
- Anaphylactic shock
- Dissociative shock
- Differentiating shock
Created by Ian Mannarino.
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- Why use methylene blue which is one of the stains used in bacteriology(study of bacteria in particular both harmless and harmful) and pathology(Study of pathogens and not harmless organisms in the same families) to reduce iron to Fe2+? Couldn't you add more of the enzyme that converts Fe3+ to Fe2+ and get less side effects from it since it is native to the body whereas methylene blue isn't?(3 votes)
- Normally this happens through the NADH or NADPH methemoglobin enzymes, methemoglobin is reduced back to hemoglobin. But when large amounts of methemoglobin occur, methemoglobin reductases are overwhelmed. Methylene blue is first reduced to leucomethylene blue, which then reduces the heme group from methemoglobin to hemoglobin. Methylene blue can reduce the half life of methemoglobin from hours to minutes.
I assume you could do what you say and add more enzyme, there is most likely a difficulty in synthesizing this enzyme in the lab and therefore probably more costly and it would be pointless to spend money when Methylene blue works so effectively.(3 votes)
- Would the effect you describe in CO poisoning be similar to that found in paraquat poisoning?(2 votes)
- The effects are entirely different. Paraquat is a poison which causes damage at a cellular level by lipid peroxidation breaking down the cell membranes leading to cell death. The kidneys and liver are particularly susceptible, as well as the lungs and red blood cells..
Carbon monoxide poisoning results from carbon monoxide taking up the receptor sites for oxygen in the haemoglobin in red blood cells; thus blocking oxygen, resulting in hypoxaemia.(2 votes)
- I want to take a moment to really acknowledge the beauty of this molecule right here. This is a heme molecule. And this little molecule allows us to deliver oxygen all throughout our body through a protein called hemoglobin. Hemoglobin is a protein with four different subunits that I'm drawing right here. And at the core of each subunit is a heme molecule. And these heme molecules have this iron group that is essential for binding oxygen. And this iron is FE two plus. And FE two plus is also known as ferrous iron. So at the core of each of these subunits is an FE two plus molecule that allows for binding of oxygen and delivery of this oxygen to the tissues. And the reason I colored this hemoglobin molecule slightly differently is because it's composed of two different types of subunits. So in each hemoglobin molecule there are two alpha subunits, and two beta subunits. The protein structure of these subunits of hemoglobin are just slightly different which allows the formation of an entire hemoglobin molecule. Now this little molecule, this hemoglobin, makes a big impact on the body. Each red blood cell has close to 270 million hemoglobin molecules. So you can see that it plays a very large role in delivering oxygen throughout the body. And of course, oxygen first comes from the lungs to jump on the hemoglobin, and then it's delivered to the tissues. So what if we somehow impaired hemoglobin's ability to deliver oxygen to the tissues? Well, what is impaired oxygen delivery to the tissues called? It's called shock. So if something impairs the ability of hemoglobin to dissociate from oxygen and drop oxygen off in the tissues, it can lead to shock. So there's an issue with oxygen dissociating, or coming off of hemoglobin, so this is known as Dissociative Shock. So let me go ahead and show you something you might be familiar with, known as the oxygen hemoglobin dissociation curve. And on the x-axis here I have written here P A O two, and what that stands for is the concentration of oxygen. And here on the y-axis we're gonna put saturation of oxygen. And so this is really oxygen saturation of hemoglobin, how saturated it is. So it makes sense, as we increase oxygen concentration, O two will probably be more likely to bind onto hemoglobin, there will be more oxygen readily available for binding onto hemoglobin. And so that can actually be seen in the dissociation curve. As the concentration of oxygen increases, the saturation onto hemoglobin increases, and as we continue to increase the oxygen concentration, the P A O two, hemoglobin will become completely saturated. So the curve will sort of plateau out at a hundred percent oxygen saturation. So now let's consider the issue of dissociative shock. If something causes decreased delivery of oxygen to the tissues from hemoglobin, so in other words, hemoglobin does not let go of oxygen, it doesn't deliver it to the tissues, it hangs onto it, right? So this would be increased binding of oxygen onto hemoglobin. So what would this look like on this curve here? Well, as we increase the concentration of oxygen, we're saying that hemoglobin binds oxygen more readily. So it will become saturated more quickly. And so we see what's called the left shift in the oxy-hemoglobin curve. And so, intuitively again, as we increase oxygen concentration, hemoglobin quickly grabs up and binds onto oxygen. So we have this increased binding of oxygen. And you might think that would be a good thing, but consider this for a moment: We can agree that the P A O two, the oxygen concentration in the lungs is very high, so at a very high level, we're pretty close to a hundred percent saturation of hemoglobin. Now in the tissues, of course, concentration of oxygen is lower. So we'll see with this dotted line here, the saturation of hemoglobin in the tissues is very low, a lot lower than it is in the lungs. So essentially, as red blood cells travel from the lungs to the tissues, they're able to drop off a lot of oxygen, they let go of the oxygen they're hanging on to. So we have this delivery of oxygen. However, let's take a look at when oxygen is bound more tightly. You'll see that the saturation of hemoglobin is all the way up here. So when you go from the lungs to the tissues on this increased binding curve, this left shift curve, we see decreased oxygen delivery, right? Only so much of the hemoglobin is letting go of it's oxygen. And so that's shock. Now a mnemonic I like to use to remember this left shifting of the curve, is that oxygen is left on hemoglobin. Now let's get back to the topic at hand. What can cause a left shift in the oxy-hemoglobin curve? Well there are two main causes of dissociative shock. And the first cause is methemoglobin, and if you have methemoglobin in your blood, it's known as methemoglobinemia. Emia means in the blood. So what the heck is methemoglobin? Well, before I emphasize that, the FE two plus form or Ferrous, is the type of heme group that you see in hemoglobin. However, there's another form of iron known as Ferric Iron. Now ferric iron is when the iron molecule is oxidized to the three plus state. Iron oxidized to the three plus state does not bind oxygen readily. So oxygen will not bind onto this Ferric heme group. If hemoglobin has a ferric iron, it's known as Methemoglobin. So methemoglobin has this FE three plus. And as I said, FE three plus cannot bind oxygen. Now that in itself could be considered pretty bad. However, having this FE three plus produces a confirmational change, or change in shape, of this hemoglobin molecule that allows oxygen to bind more readily onto these other sites. Think of it this way, there's no seat right here for oxygen, so these other oxygen molecules rush over and want to take up these other seats, because there's very limited seating. So in methemoglobinemia, we see increased ferrous iron binding of oxygen. And as mentioned before, this decreases the tissue perfusion. And so we see a left shift in the oxygen binding curve. So what causes methemoglobinemia? Methemoglobinemia is caused by nitrates. Now nitrates can be found in certain medications, in particularly antibiotics. So an example of a common antibiotic that's rich in nitrates is Bactrim, which is also known as Trimethoprim, TMP, and Sulfamethoxazole, SMX. Another common antibiotic is Dapsone. Certain anesthetics can do it, too. An example of an anesthetic that causes methemoglobinemia is Benzocaine. But medications are not the only cause of methemoglobinemia. Some pesticides have been noted to cause it. So sometimes people who drink water from wells where the ground is saturated with a lot of pesticides, they can get poisoned and have methemoglobinemia. Now what symptoms can you see in a patient who has methemoglobinemia? The symptoms are going to include signs of oxygen starvation. So beginning symptoms often include a headache, or dizziness, and as symptoms progress to more severe, patients may exhibit fatigue, or confusion, and potentially even loss of consciousness. And you can also see the typical symptoms of shock such as a rapid heart rate, tachychardia, difficulty breathing, also known as dyspnea, and other signs of organ dysfunction. Now, the treatment of methemoglobinemia will be with a medication known as Methylene Blue. So you'll give IV Methylene Blue. And what IV Methylene Blue does is aids in the conversion of FE three plus back to the FE two plus state. Oh, and I forgot a really good mnemonic to remember this: Oxygen will bind readily to the ferrous state, because it's a togetherness. Hemoglobin and oxygen makes us. However, oxygen does not want to bind to FE three plus cause it's disgusting, ick, it doesn't like the FE three plus. Now methemoglobinemia is especially dangerous for newborns. There's an enzyme that adults have known as Cytochrome B5 Reductase. Now what cytochrome B5 reductase does is it converts FE three plus to the FE two plus state, just like we see for the treatment in methemoglobinemia. So converting it back will allow oxygen to bind and dissociate correctly, like it normally should. Now, newborns have a decrease in this enzyme up until about four months old. So, if they're exposed to perhaps certain anesthetics or medications, or pesticides in drinking water, newborns may experience dissociative shock. Now to finish this up, methemoglobin is not the only cause of dissociative shock. Another major cause is carbon monoxide poisoning. So the molecule carbon monoxide has one carbon, and one oxygen, carbon monoxide. So carbon monoxide actually binds hemoglobin, HB, a hundred times greater than oxygen. So carbon monoxide actually prevents oxygen from binding onto hemoglobin in the lungs. And similar to methemoglobin, if carbon monoxide is bound to hemoglobin, then the oxygen will bind more tightly to these other subunits. So it creates a confirmational change, a change in shape, of hemoglobin, preventing the release of oxygen into the tissues. So going back down here, we have decreased oxygen delivery, which is due to increased strength of binding. However, even though oxygen is strongly binding, if another carbon monoxide molecule comes closer, it will kick off the oxygen, because, agaun, it has a hundred times more binding affinity than oxygen. So again, all of this causes a left shift in the oxy-hemoglobin curve. Now the causes of carbon monoxide poisoning really have to do with fires. Wood stoves, house fires, or any sort of combustion engine creates carbon monoxide. So long term exposure to the smoke in fires can cause carbon monoxide poisoning. And like methemoglobinemia, the symptoms are very similar. You'll start out with a headache, and dizziness, and progress to fatigue, confusion, loss of consciousness, difficulty breathing, so on and so forth. And the treatment for carbon monoxide will be a hundred percent oxygen. The idea is if you over-saturate the patient with oxygen, it can hopefully cause carbon monoxide to be kicked off of the hemoglobin molecule. So that's dissociative shock, an inability for oxygen to dissociate from hemoglobin.