You know that little “finger clothespin” that doctors put on someone’s finger to monitor their vital signs? It’s called a pulse ox, which is short for pulse oximeter because it measures (-meter) a person’s pulse and oxygen saturation. 100% oxygen saturation obviously doesn’t mean that your blood is all oxygen – instead it means that all of the copies of oxygen-carrying proteins in your blood, proteins called hemoglobin, are loaded up with oxygen. Knowing the oxygen saturation helps doctors understand how well someone’s body is able to maintain adequate oxygen delivery to all the tissues in need – and how this technique works is quite cool indeed! Especially since, unlike Arterial Blood Gasses (ABGs) it can work continuously and doesn’t require blood drawing. These techniques tell you slightly different things, and today I’ll give an overview of what each brings.

Here’s an overview of the techniques and then I’ll tell you more about the biochemistry and some more details on the techniques. Quick technical note: concentrations of gasses are often reported as “partial pressures,” which is just a measurement of how much of that gas there is, and is signified by “Pa” before the gas name. So, for example, the partial pressure of oxygen is reported as PaO₂, and uses units like kPa (kiloPascals) or mmHg (millimeters of mercury).

You can find out PaO₂ (and a couple other things) using an ABG (Arterial Blood Gas). This common hospital procedure that takes a sample of blood from a person’s artery (one of the blood vessels leaving your heart to go take oxygen (O₂) to the rest of your body) and measures a few things, including the oxygen concentration (aka oxygen content). This concentration tells you about how well the lungs are doing their job, and it depends on a few things:

  • FiO₂ (Fraction of Inspired oxygen): the partial pressure of the oxygen you breathe in (how much oxygen is in the air to begin with?)
  • how well ventilation & gas exchange is working (are the lungs doing that expand-contract-expand-contract thing they need to be doing in order to pull fresh, oxygen-rich air in & push used, CO₂-rich, oxygen-poor air out?
  • concentration of hemoglobin (how many oxygen carriers are present?)
  • affinity of hemoglobin for oxygen (how willing are those carriers to actually carry oxygen?)

Pulse oximetry (pulse ox) focuses on the hemoglobin, looking to see what percentage of the hemoglobin proteins (our oxygen carriers) are bound to oxygen. And it does this “looking” non-invasively – you just have to stick that digital finger clothespin on your finger. 

Pulse ox’s can tell based on how well specific wavelengths of light can pass through your finger. Light can be thought of as little packets of energy called photons traveling in waves. Different wavelengths correspond to photons with different energies and we perceive them as different colors. White light has all the colors of the rainbow and things look colored if they “steal” (absorb) some of those wavelengths, leaving us to see just the leftovers (which can be transmitted (let through) or reflected (bounced back at us). The molecular makeup of things determines which wavelengths those things can absorb, and different things have different molecular makeups, so they absorb different wavelengths and look different colors. 

Your blood “picks up” oxygen in your lungs – that oxygen bind to the hemoglobin protein in the blood to form a complex called oxyhemoglobin. This binding isn’t permanent (that would defeat the purpose of carrying the oxygen from the lungs where it’s aplenty to the toe where it’s harder to go), but in the bound state, hemoglobin absorbs a slightly different wavelength of light than when there’s no oxygen bound. So, by shining light through and seeing how much makes it through, the pulse ox can calculate what proportion of the hemoglobin molecules are bound to oxygen. 

You might have heard that venous blood (the blood returning to the heart) is blue because it doesn’t have oxygen. This is a myth. There are a couple reasons your veins look bluish – one is that blue light doesn’t penetrate skin as far as red light. So the blue light is more easily reflected back at us than red light. And the second reason is that, while venous blood may not be blue, it *is* less red – it’s darker than the oxygen-rich blood in the arteries leaving your heart to deliver oxygen to the body. And this is because it’s that oxyhemoglobin state that’s bright red. You still have a lot of this in your veins, just not *as much*. 

So you’re not looking for red vs. blue here, but you can use 2 different wavelengths – one the unbound hemoglobin likes and one the oxyhemoglobin likes. And then you look at the ratio of the 2 to calculate the oxygen saturation. You can’t just shine a single wavelength – that wouldn’t tell you much because the absorption will also depend on things like how big your finger is, how thick your skin is, etc. 

So you have 2 lights – one is a red light (wavelength 660 nm), which gets absorbed by the unoxygenated form (since it gets absorbed, it gets “hidden” and it does NOT look red. The oxygenated form does NOT absorb this wavelength so it DOES look red). The second is an infrared light (wavelength 940 nm) – the oxyhemoglobin likes this one, and absorbs it better than the deoxyhemoglobin does. The lights switch on-off-on-off-on-off. One goes on, then goes off and the other goes on. Then they both go off. And they do this over and over, ~30 times per second. They’re not the only thing “cycling” – the amount of arterial blood is changing with each pulse of the heart. And this offers a cool opportunity – by subtracting the minimum transmitted light from the maximum, you can account for other tissues that might be interfering but aren’t fluctuating like that (it lets you subtract out your “background noise”).

The oxygen saturation is hopefully 95-100%. If the saturation’s lower than this, the person is said to be “hypoxic” (hypo, below). You’ve likely seen this term a lot lately because Covid-19, the disease caused by the novel coronavirus SARS-CoV-2, can cause patients to become EXTREMELY hypoxic – like under 70%! 

For patients with severe Covid-19-caused pneumonia, their lungs get really “stiff” so its harder for them to suck air in and push it out. And if you can’t suck enough air in, it makes sense that your blood wouldn’t have enough oxygen and, since they can’t push air out well, carbon dioxide builds up and raises alarms in the patient’s body. But, one of the weirdest things about the disease is that, in the earlier stages, when the lungs are still working fairly normally, some patients who are super hypoxic are still acting relatively normally – talking, etc. Doctors think this might be because, although the lungs are working okay, so carbon dioxide is getting removed and stuff, little blood clots could prevent the blood from getting oxygenated well without the CO₂ “alarms” going off to alert the patient they need oxygen. 

Why is this lack of alarm so alarming? To understand the importance of oxygen, let’s dive into a bit of biochemistry!

The”cardiopulmonary system” is your heart + lungs + blood vessels + blood, etc. working together to take oxygen that’s in the air and distribute it all around your body. Even the furthest reaches in your body – the tips of your teeny toes – need oxygen in order to function normally because, among other things, oxygen plays a crucial role in energy production, as we looked at in the post on cellular respiration It’s the star player in the last step of the most efficient form of ATP production – oxidative phosphorylation and the electron transport chain. recap – ATP is a high-potential-energy molecule that our cells use as a form of energy “coin” that can be made from a variety of fuels (fats, carbs, etc.) and spent on all sorts of things like making proteins and copying DNA). The electron transport chain drives ATP production by passing electrons from one molecule to another to another to another to OXYGEN! Without oxygen there to drive the process, it shuts down (your body can make some energy through anaerobic (non-oxygen-requiring) respiration, but you make a lot less ATP that way, and you also get the buildup of byproducts like lactic acid). 

That cellular use of oxygen for making energy is called “cellular respiration” but, outside of biochemistry, the term “respiration” is more  commonly used to refer to pulmonary respiration. Pulmonary refers to lungs and this type of respiration is where your lungs expand to suck air in and then contract to push used air out. Lungs are often depicted as big sack-like things, but within those “sacks” are branching tubes leading to lots of tiny grape-like ends called alveoli, which are surrounded by tiny blood vessels (capillaries) where gas exchange can occur. The sucked-in air contains oxygen and a protein called hemoglobin in the blood in the capillaries surrounding the alveoli grabs onto that oxygen and whisks it off. To help give it the energy it needs to get to your toes, the next step is your heart, which, through its pumping, gives that oxygenated blood a push out.

But how does hemoglobin know where on its route to give oxygen out? A lot more details on hemoglobin yesterday, but it’s basically just seriously amazing… And the amazingness (like many amazing things) all comes from biochemistry, which many an amazing thing does bring!

The hemoglobin protein is a “tetramer” –  it’s made up of 4 protein chains working together to form a functional protein. But this “globin” is not functional unless it has help from a cofactor (bound, non-protein molecule) called heme. The globin protein holds onto heme (one per chain, so 4 total per hemoglobin) and heme holds onto iron and they all work together to hold onto oxygen. And they *really* work together – hemoglobin’s oxygen-binding is a great example of “cooperativity” – when none of the sites are bound to oxygen, hemoglobin isn’t that eager to grab oxygen. But when one of the 4 sites binds, it causes the protein to shape shift a little so that it’s easier for the other 3 sites to bind. And, when one of the sites lets go, the other sites are quick to follow. 

You can think of it kinda like peer pressure on the molecular scale, and it leads to a sort of all or nothing approach, which you can visualize with a hemoglobin-oxygen dissociation curve plotting hemoglobin saturation (y-axis) against oxygen concentration. As the available oxygen levels increase, it becomes more likely that one site will bump into an oxygen molecule and bind, leading to the shape shift which makes it easier for the others to follow suit. So you see an S-like curve. 

Normal room air contains ~21% oxygen (in geek speak it has an FiO₂ of 0.21), but If someone is having oxygenation problems, doctors often give them “extra” oxygen to try to get their hemoglobin to the right side of the curve. This works well if you’re on the left side of the curve, where there’s still a lot of hemoglobin open, but not enough oxygen’s getting there, but as you can see, if you’re already on the right side of the curve, and the hemoglobin’s full, that oxygen won’t help much. And it also won’t help if the lungs can’t suck in that oxygen-rich air (that is, there’s a problem with ventilation). Instead, the lungs might need help expand-contract-expand-contract-ing, which is where mechanical ventilators can help. “Gentler” methods of providing pressure like CPAP & BiPAP, which work via face masks instead of tubes down in your lungs, can help the air get down into those alveoli. 

Assuming that all is normal, In your lungs, there’s a lot of oxygen, so the hemoglobin “all” binds – but in your toes, there’s less oxygen because you’re further from the source and some of it’s been delivered along the way. Since there’s less oxygen, the hemoglobin is more likely to dump some out, especially thanks to something called the Bohr effect, which we discussed in detail yesterday, but here’s the gist: making energy doesn’t just use oxygen (O₂), it also produces carbon dioxide (CO₂). When that CO₂ dissolves, it produces carbonic acid, which makes the blood more acidic and lowers hemoglobin’s affinity for oxygen, making it more willing to dump it out.  

An Arterial Blood Gas (ABG) don’t just measure the oxygen (the PaO₂, which in case you’re wondering is usually 75-100 mmHg), it also measures the CO₂ and the pH (a measure of acidity) to report on acid-base balance. You might be wondering why you need to measure both CO₂ and pH, since I just told you that CO₂ can dissolve and decrease the pH. Thing is, your body  doesn’t want the pH to go too low (a condition called acidosis, so it has great “buffering” capacity – it can add base in the form of sodium bicarbonate (HCO₃⁻). But if it “adds too much” the pH can get too high, a condition called alkalemia (normal pH is ~7.4). Typically, acidemia is below 7.35 and alkalemia is above 7.45.

The pCO₂ (which should be 35-45 mmHg) can be used to calculate what you’d expect the pH to be and then you can compare it to the actual pH to figure out the “base excess” (BE), but it’s usefulness is controversial, so I’m not gonna go into more detail. If you want to learn more about these things: 

There are exceptions to everything because the human body is full of surprises and tricks up its sleeves, but If the pH is low AND the pCO₂ is high, that points to respiratory problems. But if the pH is low and the pCO₂ is also low, or at least not high, that points to the problem being “metabolic” (metabolism referring to molecular making and breaking – so basically some biochemical pathway is acting up, and it’s likely not the cardiopulmonary system’s fault). 

Be careful not to confuse oxygen concentration (aka oxygen content) with oxygen saturation. The total oxygen concentration tells you how much oxygen is in the blood, without taking into account how much hemoglobin is present, so you could potentially have “extra” hemoglobin working at reduced capacity and still have a “normal” oxygen concentration. The oxygen saturation tells you about how “at capacity” the hemoglobin is – so, in that above scenario where you had “extra” hemoglobin working at reduced capacity, that would show up as a lower oxygen saturation. 

But – what if you had low hemoglobin working normally? You wouldn’t see that in the oxygen saturation, but you would see that in the oxygen concentration. 

So both have value, and some blood gas analyzers (the machines that measure the oxygen, carbon dioxide, and pH for the ABG) also measure oxygen saturation directly in a similar manner to the pulse oximeter – but other ABGs report calculated oxygen saturation based on the assumption that hemoglobin content is normal. Oxygen content (concentration) is often expressed in mL O₂/100mL of blood or O₂/L of blood, with the maximum (the carrying capacity) being about 20mL oxygen/100mL blood. But most of that oxygen is bound to hemoglobin. In the arterial blood of a healthy individual, about 96-98% of hemoglobin’s oxygen-binding sites are oxygen-bound. 

I’ve been talking about arterial blood because the situation in your veins, the blood vessels returning all the “used” blood to your heart, is a different story. There, because of reasons including less oxygen (lower partial pressures) and lower pH (greater acidity), a lower proportion of hemoglobin is oxygen-bound. It varies, but is typically about 75% – so there’s still quite a bit which is good if you need to hold your breath or something, or your muscles are working overtime!

Speaking of working overtime, time for some fun-doing for today (paper-reading, family Zoom gaming, figure-making, etc.). Hope you can find some fun to do too!

And – standard warning – I am NOT a doctor – not even a nerd one (PhD) YET. So hopefully I got it all right and your real doctors know this technical stuff better than I do! 

more on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉

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