Diffusion-limited and perfusion-limited gas exchange

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Introduction0:00–0:36

The primary role of the lungs is to ensure gas exchange between the external environment, and the blood within the circulatory system.
This happens thanks to a series of branching tubes called airways, which conduct the air down into small thin-walled sacs called alveoli, which are wrapped in an intricate network of tiny blood vessels called pulmonary capillaries.
And the alveolo-capillary membrane, where the layer of alveolar cells lining the alveoli meets the endothelial cells that make up the pulmonary capillary, is where gas exchange occurs.

Ficks law0:36–1:25

Now, before we delve into diffusion, perfusion and their limits, remember that gas exchange across the alveolo-capillary membrane happens according to Fick’s law.
Fick’s law states that the net rate of diffusion - V of any particular gas across the alveolar-capillary membrane, is proportional to the pressure gradient across the wall; which is the difference between the partial pressure of the gas in the alveolar sacs, or PA, and the partial pressure of the gas in the blood, or Pa, and also proportional to the surface area of the wall, or A, but inversely proportional to the wall’s thickness - T.
And this is all times the diffusion constant - D, which varies from gas to gas. V=(PA-Pa)ADTSo, diffusion-limited gas exchange means that a gas like oxygen or carbon dioxide can diffuse across the alveolo-capillary membrane as long as the partial pressure gradient is maintained.

Gas exchange1:25–2:24

On the other hand, perfusion-limited gas exchange means that if the pressure gradient is not maintained, and the concentration of gases on the two sides of the alveolo-capillary membrane becomes the same, further gas exchange is only possible by increasing blood flow, or perfusion, in the pulmonary capillary.To understand these concepts, let’s look at a section of an alveolar sac, with a pulmonary capillary running along its surface.
The capillary carries mixed venous blood, which is low in oxygen and high in carbon dioxide. As blood passes along the alveolar capillary wall along the length of the capillary, it exchanges some gas molecules with the interior of the alveolar sac.Let’s look at perfusion-limited gas exchange first.

Perfusion-limited gas exchange2:24–5:41

In this case, the total amount of gas that diffuses into the blood depends on the amount of blood flowing through the pulmonary capillaries around the alveoli.
The best example to illustrate this is by using Nitrous oxide, or N2O gas. So imagine we’re inflating the alveolar sac with nitrous oxide, and that its partial alveolar pressure, noted as PAN2O is constant.
At the beginning of the alveolar-capillary contact, the partial pressure of nitrous oxide in the pulmonary capillary blood, or PaN2O, is zero, because this gas doesn't initially exist in the blood.
According to Fick’s law, this pressure gradient makes nitrous oxide molecules from the alveolar sac rapidly diffuse into the pulmonary capillary.
Within the blood, nitrous oxide molecules don't bind to hemoglobin or other blood components, so all the gas molecules are free in the blood, which makes the partial pressure of nitrous oxide in the pulmonary capillary blood rise quickly.
In fact, this happens so fast that by the first one-fifth of the capillary length, the equilibrium between the partial pressures on both sides of the alveolo-capillary membrane is already attained.
At this point, the partial pressure gradient falls to zero, so nitrous oxide diffusion stops. In this situation, the only way to increase the net diffusion is to increase blood flow through the pulmonary capillary.
Increased blood flow rushes nitrous-oxide rich blood through the capillary, and brings in new blood with no or less nitrous oxide in it, restoring the partial pressure gradient.
Another example of perfusion limited gas exchange can be illustrated by oxygen, but only under normal circumstances - so this doesn’t apply during strenuous exercise, or in the case of lung disorders like fibrosis or emphysema.
Just your regular, run of the mill oxygen diffusion. Alright, so at the beginning of the alveolar-capillary contact, the partial pressure of oxygen in the alveoli, or PAO2, is higher than that which comes within mixed venous blood in the pulmonary capillaries, which is noted as PaO2.
This creates a partial pressure gradient, which makes oxygen diffuse into the blood. As the process continues, the partial pressure of oxygen in the pulmonary capillary blood rises, but not as quick as with nitrous oxide.
This is because, unlike nitrous oxide, newly diffused oxygen molecules bind to hemoglobin in red blood cells, so first, all hemoglobin molecules have to become saturated with oxygen, before free oxygen molecules appear in the blood and PaO2 increases.
This pushes the point of equilibrium between PAO2 and PaO2 at around one-third of the capillary length, a bit further compared to one fifth in N2O.
From here onwards, unless the rate of blood flow increases to bring in more of oxygen-hungry blood, no more net diffusion of O2 can occur.Now, on the other hand, there’s diffusion-limited gas exchange, which is best illustrated by using the example of carbon monoxide, or CO, diffusion.

Diffusion-limited gas exchange5:41–7:29

OK, now, at the beginning of the alveolar-capillary contact, we have the highest alveolar CO partial pressure, or PACO, while its partial pressure in the blood, or PaCO, is zero because this gas isn't originally found in the blood.
At this point, the partial pressure gradient is at its highest, and this causes CO to quickly diffuse into the blood. When CO gets into the blood, it avidly binds to hemoglobin within the red blood cells, so there’s very little free unbound CO.
This causes partial pressure of CO in the blood to rise just a little bit. In fact, it rises so little, that even at the end of the capillary length, the equilibrium between alveolar CO partial pressure and partial pressure of CO in the blood is not achieved.
So the pressure gradient is sustained along the entire length of the pulmonary capillary, making this a case of diffusion-limited gas exchange.
Diffusion-limited gas exchange also applies to oxygen under special circumstances, like during strenuous physical exercise.
In this situation, heart rate increases, the speed of pulmonary blood flow increases, and this shortens the transit time for the blood near the alveolar-capillary wall.
So there’s no time for partial pressure of oxygen in the blood to reach the partial pressure of oxygen in the alveolar sac.
This keeps the pressure gradient up and running, making it a type of diffusion-limited gas exchange.Oxygen exchange is also diffusion limited in the setting of lung conditions like lung fibrosis or emphysema.
In lung fibrosis, the alveolar-capillary wall thickens. And according to Fick’s law, a thicker alveolo-capillary membrane reduces the rate of diffusion, so it takes much longer for the partial pressure of oxygen in the blood to reach the partial pressure of oxygen in the alveolar sac.

Pathologies7:29–8:29

This means that blood flows through the entire length of the capillary with a pressure gradient in place that’s high enough to maintain diffusion.Finally, there’s emphysema.
With emphysema, the alveoli are gradually destroyed, which reduces the total surface area that allows gas exchange. And according to Fick’s law, if there’s less surface area for gas exchange to occur, the rate of diffusion decreases.
This maintains a high partial pressure gradient high, so it’s another example of diffusion-limited gas exchange.Alright, as a quick recap...diffusion-limited and perfusion-limited gas exchange are two instances that alter gas exchange across the alveolo-capillary membrane.With perfusion-limited gas exchange, the partial pressures across the alveolar-capillary wall equilibrate before blood leaves the pulmonary capillaries, which results in a null pressure gradient.
Increasing diffusion in this case requires increasing the rate of blood flow in pulmonary capillaries. On the other hand, with diffusion-limited gas exchange, the partial pressures across the alveolar-capillary barrier do not equilibrate, because the gas molecules bind to some blood components, like hemoglobin.

Review8:29–9:33

So there’s very little free gas in the blood, which exerts a minor partial pressure, too small to balance the one in alveolar sacs.
This sustains the pressure gradient along the entire length of the pulmonary capillary, making it a diffusion-limited gas exchange.
partial pressure is across the alveolar. Capillary barrier did not equilibrate because of gas molecules bind to some blood components like hemoglobin.
So there's very little free gas in the blood which exerts a minor partial pressure too small to balance the one in the alveolar, sacs.
This is James, the pressure, gradient along the entire length of the pulmonary, capillary making it diffusion limited. Gas exchange.