Hypoxia

Hopefully by now we are starting to develop a healthy appreciation for oxygen delivery – why it is so important, how it can be augmented, and the limitations that exist. We have also discussed that when this process starts to break down (i.e., when oxygen delivery is compromised in cardiac/respiratory failure), we must optimize oxygen delivery through critical care interventions, which can come with a cost.

Let’s briefly return to our consideration of oxygen delivery and hemoglobin binding. In Chapter 1 , we explored how oxygen would bind to hemoglobin and how important the oxygenated hemoglobin molecule was to the delivery of oxygen. Now we will explore what happens when there is less oxygen readily available to be able to bind and saturate hemoglobin ( Fig. 4.1 ).

How does oxygen enter the body?

Take a deep breath in. Go ahead, I’ll wait … now let it out. What is happening when we do this simple function? With every breath in and every breath out, we are allowing oxygen to enter our body, we are enabling the delivery and use of that oxygen, and we are expiring carbon dioxide, the byproduct of that metabolism. This happens like clockwork, hundreds of times per hour, every day, whether we are conscious of it or not. None of this would be possible if there was not a ready and efficient way for oxygen to enter the body and carbon dioxide to exit.

To explore how this happens, follow that breath of air in – through the airway, past the bronchi, through the bronchioles, all the way down until we get to the level of the alveoli. It is at this level that gas exchange between the lungs and the blood is able to happen in an efficient manner, by setting up an interface between the blood vessels and the alveoli.

Due to the close proximity of the blood and the alveoli, this interface allows for diffusion of gases down their respective concentration gradients. Just like if you dropped a drop of dye into a glass of water, diffusion allows molecules to go from areas of high concentration to areas of low concentration. It is this diffusion gradient that drives the flow of oxygen and carbon dioxide in such a manner that oxygen is able to enter the body and carbon dioxide is able to leave the body ( Fig. 4.2 ).

It is important to separate these two components of respiration out (ventilation of the alveoli and perfusion of the blood vessels) because they become vital to our discussion and allow us to better identify the level of the deficiency.

When the system breaks down

There are a host of reasons for low concentrations of oxygen in the blood. These can include hypoventilation, low inspired FiO ₂ , as is seen at high altitude, and diffusion defects where there is a breakdown at the level of the interstitium. The purpose of our discussion is to better understand the two components of the alveolar-blood interface, and how they interact with each other.

Deficiency at the level of the alveolus is labeled V by convention, whereas deficiency at the level of blood to perfuse the alveolus is labeled Q. If both are equally contributing to gas exchange, then the ratio of V/Q is equal to 1 ( Fig. 4.3 ).

When there is a deficiency of one relative to the other, there is V/Q mismatch. Let’s look at two permutations.

In Chapter 2 , we described in detail the specifics of when and how the right heart can fail. Now let’s consider the effect of a decline in right heart function on respiratory function.

If there is a decline in the right ventricular function, the overall perfusion to the alveolar-blood vessel apparatus will decline. That means that on some level, whether just through decreased perfusion or the total lack of perfusion, there will be V/Q > 1. This manifests as an alveolar unit where is fully ventilated but does not participate in gas exchange. It is as if there is no connection between the two – air comes in and out with no improvement in ventilation. This is referred to as “dead space” ( Fig. 4.4 ).

Let’s contrast this with the opposite scenario, where V/Q < 1. This would correspond with any time when there is decreased ability of air to enter into the alveolar component of the alveolar-blood vessel interface – pneumonia, edema, mucous plugging, etc. In this case, blood traverses across the interface with no ability for gas to diffuse. In this manner, this is referred to as “shunt” ( Fig. 4.5 ).

Although the temptation is to think of the lungs as a homogenous collection of alveoli and the pulmonary circulation similarly as a uniform collection of blood vessels perfusing these alveoli, the situation can be quite complex. There can be areas of the lung with profound V/Q mismatch, such as complete collapse of one lobe of the lung due to mucous plug, for example. In this case, the collapsed area of the lung may have a V/Q much less than 1, while the remainder of the lung may have normal matching of ventilation to perfusion.

Consider also that even under normal conditions, blood tends to be gravity dependent leading to increased distension of the pulmonary blood vessels in the lower portions of the lung (and thus V/Q < 1), while alveoli may be more distended in the upper areas of the lungs (with V/Q > 1) ( Fig. 4.6 ).

So why make this distinction?

We distinguish aberrations in the V/Q matching in this way, because the physiology is very different. Just like the models for shock, this classification should help to develop an approach for thinking about respiratory failure, which can then be built upon. Specifically, let’s examine the case of hypoxia and the role of mechanical ventilation.

There are many reasons to undergo mechanical ventilation – inability to protect airway, excessive secretions, expected clinical course, etc. However, in order to best understand the breakdown of the delivery of oxygen due to respiratory failure, we will focus our discussion on the role of mechanical ventilation on improving hypoxia due to shunt, where V/Q is less than 1. Let’s now focus in on shunt, its specific physiology, and the role of mechanical ventilation in mitigating the ensuing hypoxia.

What does hypoxia due to shunt look like?

Shunt is important to recognize and understand because its physiology is unique.

While we have talked about the alveolar-blood vessel interface as one unit, there are millions of alveoli in the lungs, so when we talk about shunt physiology, we are acknowledging that this physiology exists as a spectrum, becoming more profound as more shunting occurs.

Let’s start by understanding what happens with normal lungs, with minimal shunt. If no shunt exists, every alveoli is paired with a perfusing blood vessel and the maximum interface between those two is maintained. If you were to spread out the surface area of this interface, it would be the size of a tennis court, so you can quickly understand how the lungs can be so efficient at allowing oxygen to diffuse into the blood.

Not only are our hypothetical lungs with no shunt able to allow for a higher diffusion of oxygen at room air, but when we add higher concentration of inspired oxygen (FiO ₂ ), we really start to see the difference. Because there is so much more area for oxygen to diffuse across, increasing the FiO ₂ by a multiple of two-, three-, or fourfold not only increases the amount of oxygen that diffuses across but it does so at an exponential rate.

Now, let’s consider what happens when there is 10% shunt. In this case, there is a slightly lower amount of oxygen that can diffuse across at room air, as noted by the lower PaO ₂ . However, as we increase the FiO ₂ , say from 2 L nasal cannula to 6 L to a non-rebreather face mask, there is going to be an increase in PaO ₂ of the blood almost as high if there was no shunt – however, notice that it takes a higher FiO ₂ to get there!

As the amount of shunt progresses, notice that it not only corresponds to a lower initial PaO ₂ at room air but also to a more shallow slope of the line, with decreasing gains in PaO ₂ for every escalation in FiO ₂ ( Fig. 4.7 ).

Notice what happens when we arrive at approximately 50% shunt. At this point, you can observe that the curve is essentially flat. This means that no matter how much oxygen you give, there will be no subsequent increase in oxygen that diffuses along to the blood. This pattern is what is meant when we say “shunt physiology” – the point where adding more inspired oxygen will not help increase the blood oxygen concentration, no matter how much is given ( Fig. 4.8 ).