Oxygen Delivery and Consumption

Imagine that you walk into a typical intensive care unit (ICU). You look around and note what you see: in one room a 78-year-old man with urosepsis and septic shock, in the next room a 65-year-old woman with a chronic obstructive pulmonary disease exacerbation, in the next a 55-year-old man with cirrhosis and a gastrointestinal bleed, in the next a 45-year-old man with non-ST-elevation myocardial infarction and intermittent runs of ventricular tachycardia…

The list goes on and on.

What do all of these patients and, frankly, any patient admitted to the ICU have in common? They all have very different pathology, medical histories, and modalities of support that they are requiring.

However, all of these patients are in the ICU because they have a deficiency or are at risk of having a deficiency in their ability to deliver oxygen. This is tremendously important to recognize about our patients – the common reason for critical care interventions is a deficiency in the delivery of oxygen. The better we understand the concept of how oxygen is delivered, the better position we are in to define and support this delivery of oxygen.

How is oxygen delivered in the body?

Have you ever wondered why it is that the tissue that surrounds the heart and lungs is not preferentially oxygenated, compared to the tissue in the periphery ( Fig. 1.1 )?

At first glance, this is what you might expect. After all, the tissue surrounding the heart and lungs is located centrally and has the nearest proximity to oxygen when it first comes into the body. Indeed, if oxygen was distributed throughout the body by diffusion, then this would be the case.

What do I mean by diffusion? Diffusion is the movement of molecules down their concentration gradient from high concentration to low concentration.

Think of how oxygen enters the body in the lungs – you take a breath in and air enters through your nose/mouth, down your trachea, across your bronchi, all the way to the alveoli. At this point the oxygen diffuses into the blood, going from an area of high concentration (the alveoli) to an area of lower concentration (the blood) ( Fig. 1.2 ).

For many organisms such as bacteria, amoebae, and some jellyfish, this process of diffusion is the primary mechanism for the distribution of oxygen. However, all higher levels of function/life are dependent on a more efficient process for oxygen delivery.

Why is diffusion inefficient at delivering oxygen? Let’s start by sketching the potential relationship of oxygen delivery by diffusion. If we were to do so, we might expect something that looks like ( Fig. 1.3 ), with a relatively straight line that slopes up, with more delivery of oxygen at higher concentrations and less delivery of oxygen at lower concentrations.

If this were how oxygen were delivered, you would not anticipate much efficiency, as tissues that were present at higher oxygen concentrations (the right side of the line) would have the majority of O ₂ delivered and tissues that were present at lower oxygen concentrations (the left side of the line) would have less oxygen delivered. Fortunately, there is a much more efficient means of delivering oxygen.

What allows for efficient delivery of oxygen throughout the body?

If you were inventing a way to ideally deliver oxygen throughout the body, you would want to have a system that would bind preferentially to oxygen, when there is an abundance of oxygen and dump preferentially, when there is less presence of oxygen. Returning to our graph, you may ideally expect something like the gray lines below, where there is a lower inflection point, allowing for less delivery/higher binding at high concentrations of oxygen and an upper inflection point, allowing for more delivery/higher dumping at lower concentrations of oxygen ( Fig. 1.4 ).

Any system that features these two inflection points would be vastly superior and allow for a much more efficient means of delivering oxygen. Fortunately, this is not just an arbitrary thought exercise but, rather, describes the molecule that lies at the center of oxygen delivery – hemoglobin!

How does hemoglobin allow for more efficient oxygen delivery?

Remember the ideal molecule for delivery of oxygen has two properties:

1.

Preferentially bind when there is an abundance of oxygen

and
2.

Preferentially dump when there is a scarcity of oxygen

Let’s explore how hemoglobin is able to accomplish both of these goals.

Hemoglobin and oxygen binding

Hemoglobin is a dynamic molecule, which carries with it the ability to fold its proteins and change conformation. Its proteins form a bond with oxygen allowing up to four oxygen molecules to bind to each hemoglobin molecule ( Fig. 1.5 ). However, that is only half the story.

Rather than simply binding to oxygen, the hemoglobin molecule carries with it the ability to change its structure based on how much oxygen is bound to it. If a hemoglobin molecule comes into contact with an oxygen molecule, it will bind as noted earlier. However, once it is bound to the first oxygen molecule, hemoglobin changes conformation in such a way that it will bind more strongly to the second O ₂ that comes along than the first. Hemoglobin then changes again – the third O ₂ is more likely to bind than the second, and the fourth O ₂ is more likely to bind than the third.

You can see that this property causes a positive feedback loop, so that as more O ₂ comes in contact with more hemoglobin, the amount bound not only increases, but increases in an exponential fashion.

The effect of this is a higher degree of oxygen binding at higher oxygen concentrations ( Fig. 1.6 ).

Hemoglobin and oxygen dumping

Remember, hemoglobin binding in the presence of oxygen abundance is only half the story. The other half is that hemoglobin must also dump oxygen in the periphery, where there is less oxygen available.

Let’s now explore this property of hemoglobin.

The hemoglobin proteins can exist in both a tensed form and a relaxed form. Imagine it as a rubber bowl that can be stretched causing its contents to be spilled out. When hemoglobin exists in the tensed form, oxygen spills out and is dumped for delivery/consumption.

Ideally this tense form would exhibit itself more preferentially in the periphery, which is exactly what happens! This taut form is induced in the presence of higher temperature, lower pH, and higher CO ₂ – all conditions common in the periphery ( Fig. 1.7A ). Thus, each hemoglobin molecule is more likely to be in the tense state and thus dump its oxygen contents in the periphery where there is likely to be less oxygen available ( Fig. 1.7B ).