Alright, buckle up because this is too long and as an added bonus is uninteresting. Still though, let’s take a crack at COVID-19 and your hemoglobin.
COVID-19, biology and hematology
I’m sorry for being blunt, but this new virus is a real monster.
Yes, I know, this falls under the heading of, “Hey thanks, Dr. Obvious, for pointing out that fact, because I don’t have toilet paper and everybody I know is either working from home, furloughed, or out of work entirely.”
Fair enough, but let me explain further why this bug is acting even worse than your standard influenza or pneumonia; new research has come to light as to why COVID-19 is far more problematic than your standard issue respiratory virus. It’s actually caused me to get into two topics that I really don’t like, which are biochemistry and hematology, or the study of the blood. I should tell you two things before you read this:
- The following information is still being researched and is NOT FOR SURE. This stuff may very well change.
- A failing grade on a medical school exam was anything below 70%. I failed one exam in medical school…just one. And it was Exam I in hematology. I wasn’t good at hematology then and I’m still not good at it now. I feel like I should tell you these things in the interest of transparency. But, I do know enough to understand the mechanics of the science and how it can be impacted by COVID-19.
Okay, now that’s out of the way, I should also tell you that this post is kind of technical to the point where it’s harder to read than some of the other ones. I promise I will try to do my best and make hematology a little bit easier to understand because, quite frankly, there are relatively few in the entire universe who find hematology interesting (I’m not one of them). And it is the first syllable in that word—heme—that is the issue here. Also, if you haven’t read my post about the mucociliary elevator/escalator, do so now because this will make a lot more sense if you know how that works. I’ll wait…
Hemoglobin, the oxygen-transporting molecule in your blood
Did you read it? Good. So the oxygen from the outside air has gotten into the alveoli and now you need to get it from the lungs to all of the different tissue in your body. The biochemistry as to why you need oxygen in your tissue is tearfully boring, so never mind that right now. But if you don’t know, your red blood cells (RBCs) contain hemoglobin. Hemoglobin is the oxygen-transporting molecule in your blood. See, the oxygen doesn’t just float around your blood…you need a specific molecule to take it where it needs to go. Basically, the oxygen binds on to the hemoglobin and then unbinds when it gets to tissue. One molecule of hemoglobin can accept four molecules of oxygen.
In order for this to work, the pressure of oxygen (called the partial pressure of oxygen or “Pa02”) needs to be higher in the alveoli than on the hemoglobin molecule. When that happens, an oxygen molecule can “jump on” an “empty” hemoglobin. But see, then something magic happens: When one O2 gets on the hemoglobin, all of a sudden the hemoglobin can bind three more O2 molecules really easily without raising the O2 concentrations around it. This is really important because you don’t have to rely on higher and higher oxygen concentrations to get more oxygen on a hemoglobin. The same oxygen concentration (PaO2) in the alveoli can bind extra O2 onto the oxygen-carrying molecule without an increase in oxygen concentration around it. This is a really big deal and you couldn’t do that if hemoglobin wasn’t built like it is.
This is really important because you don’t have to rely on higher and higher oxygen concentrations to get more oxygen on a hemoglobin. The same oxygen concentration (PaO2) in the alveoli can bind extra O2 onto the oxygen-carrying molecule without an increase in oxygen concentration around it. This is a really big deal and you couldn’t do that if hemoglobin was built like it is.
I promise I’m going somewhere with this.
So now you’ve got this fully loaded hemoglobin molecule which is pumped out of the heart and towards whatever tissue might need it. And so let’s say our hemoglobin molecule makes its way to your diaphragm (that’s the muscle that pulls down so that you can breathe).
Now we have an interesting problem: How do you get the oxygen off of the hemoglobin? See, the hemoglobin is still hanging on to the O2 tightly (failure to do this would be catastrophic for reasons that would lengthen this post out even longer than the unreasonable length it already is). You have to press a button to release the hemoglobin, and we can do just that. This, actually, is really cool. Your body is designed so well that when tissue starts to run out of oxygen, it becomes acidotic. When it does that, it makes two products: Protons and 2,3-BPG. And you need both because there are two problems here:
- You need to release the oxygen and
- You need to make sure the oxygen doesn’t bind back to the hemoglobin when it gets kicked off.
2,3-BPG latches on to the hemoglobin and “pushes the button” to release the hemoglobin. The protons bind on to the hemoglobin that no longer has oxygen attached and makes it so that the now-released oxygen doesn’t hop back on the hemoglobin. The oxygen stays around the muscle tissue and your diaphragm keeps working and you keep breathing and you stay alive.
Okay. Deep breath (get it?). So just what does all this have to do with COVID-19?
Well, this maybe is the reason the virus is so challenging.
Does COVID-19 attack your hemoglobin?
There is research that suggests COVID-19 isn’t just stopping the mucociliary elevator and stopping the beating of the cilia and causing the alveoli to flood…it’s ALSO attacking your hemoglobin.
Research from some Chinese scientists (in particular, Wenzhong Liu and Hualan Li) has suggested that COVID-19 is attacking one of the four sites on hemoglobin that binds the oxygen.
Think about what that does.
When you can’t get one bound easily, it won’t bind the other three. Remember the magic trick your hemoglobin does by the alveoli?
So, your hemoglobin doesn’t bind the oxygen and the RBC runs right through the capillary and out the other side. See, don’t forget that your red blood cells and their hemoglobin only get one shot at this when they get to the lungs. It’s not like they can stop and wait longer for the oxygen to bind or turn around and go back because they didn’t get any oxygen when they went through. I’ve probably been applying too much personality to red blood cells and hemoglobin; they don’t think, they merely obey the laws of biochemistry.
So, not only does COVID-19 potentially cause a pneumonia because of the mucociliary escalator problem, it also (maybe) stops your ability to carry the oxygen that DOES manage to get across the alveoli. And I’m afraid it doesn’t stop there.
COVID-19 may not just inhibit binding of oxygen to the hemoglobin chains, it may actually break the chains down all together. If this were a ship and Jack Dawson were on it, he would say in stark realization, “This is bad.”
Free iron
When hemoglobin chains break down, they release free iron into the tissue around it. Free iron (specifically ferrous iron, or Fe2+) causes something called a redox reaction. The point is, free iron is toxic enough to your tissue that your body makes a special transporting molecule called ferritin to move around with. Ferritin is your lead-lined briefcase for the radioactive plutonium (which in this case is the ferrous iron).
When hemoglobin chains break down, they release free iron into the tissue around it. Free iron (specifically ferrous iron, or Fe2+) causes something called a redox reaction but we don’t need to go into that because we’ve had quite enough biochemistry today. The point is, free iron is toxic enough to your tissue that your body makes a special transporting molecule called ferritin to move around with. Ferritin is your lead-lined briefcase for the radioactive plutonium (which in this case is the ferrous iron).
So, COVID-19 stops your ability to move oxygen into your blood stream. It stops your ability to move the oxygen that manages to get in regardless. And lastly, it breaks down your oxygen-moving molecules, which are toxic to the tissue around them when they break down.
Now there is the question, “What about hydroxychloroquine?” I actually get why this is being studied. On the surface, it seems like something that might be good. After all, malaria—the disease it’s prescribed for—is characterized by hemoglobin breakdown, impaired oxygen transport, and toxic damage from the hemoglobin breakdown—two of the three things that COVID-19 might be doing. So I get why people are hopeful. Here’s the problem:
- Malaria is caused by a bloodborne parasite, not a virus. They’re two entirely different infectious organisms and the two don’t work the same way.
- Hydroxychloroquine targets a specific aspect of the malaria parasite’s (Plasmodium vivax, P. malariae, P. Ovale…etc) lifecycle. Okay, what I’m telling you is that it’s going after something specific to a parasite in a blood cell. A virus in no way has any of the things that hydroxychloroquine targets.
Now, hydroxychloroquine may decrease some of the inflammatory reactions that occur but here’s the point: Hydroxychloroquine isn’t coming in like a knight in shining armor to save you. The only thing that’s going to save you is you. By staying home even when you don’t want to.
But if you read this far, you were almost certainly already doing that.
The expert family medicine providers at the Des Moines University Clinic are here to help you and your loved ones stay healthy year-round. If you think you or your family have been infected with COVID-19 and live in Polk County, call 2-1-1. If you have an upcoming appointment at the DMU Clinic please call in advance. More information is available on DMU’s coronavirus response website.