Sunday, May 1, 2016

Gas Exchange and Transport

This lecture also looks like there's a lot to talk about (judging by the number of slides), though the content is probably a bit easier. So we'll see how things go.

Know the composition of air

The composition of air is usually around 78% nitrogen and 21% oxygen, with the remaining 1% made up of other gases such as carbon dioxide (0.04%) and water vapour (0.5%).

Fun fact: food blogger fearmongerer Food Babe once whinged about aeroplane air not being pure oxygen, because it's "mixed with nitrogen, sometimes almost 50%." This earned her a lot of ridicule, and rightly so. She's taken the post down but there's a lot of places where you can read about it, for example at http://theness.com/neurologicablog/index.php/food-babe-misinformation-on-travel/. (And if you've never heard of Food Babe, good. Her fear of "anything chemical" probably won't do your science degree any good. -insert dihydrogen monoxide joke here-)

To find the partial pressure of a particular gas in the air, all you need to do is multiply the percentage of that gas by the atmospheric pressure. At sea level, atmospheric pressure is around 760mmHg. Hence the partial pressure of oxygen at sea level is 760*0.21 = 160mmHg.

Partial pressures of gases might be somewhat different once inspired, though. This is because air is humidified as it makes its way into the lungs, so the partial pressure of water climbs its way up to 47mmHg. To find the partial pressure of inspired oxygen, you use the same equation as before, but you have to subtract 47 from 760 to account for the fact that 47mmHg of that total pressure is now made up of water vapour. Hence the partial pressure of inspired oxygen at sea level is (760 - 47)*0.21 = 150mmHg. (You can use the same equation to find the partial pressure of other gases- you just need to substitute 0.21 for the percentage of the gas that you're interested in.)

Discuss diffusion capacity


Diffusion capacity (DL) is essentially a measure of how readily the gas diffuses across the membrane. This is affected by several factors: surface area of the alveoli (larger is better), the partial pressure gradient across the membrane (larger is better), thickness of the membrane (thinner is better) and diffusion constant. This final variable, diffusion constant, is determined by solubility and molecular weight. In fact there's a nice little equation for it: the diffusion coefficient D is directly proportional to sol/sqrt(MW), where sol is solubility and MW is molecular weight. Let's discuss all of these in a little more detail:

Surface area

Not much needs to be discussed here. Alveoli have a massive surface area and shitloads of capillaries to make it easier for gases to be exchanged across the membrane.

Partial pressure gradients

As you should well know by now, gases diffuse down a diffusion gradient from an area of high concentration to an area of low concentration. The steeper the gradient, the faster the movement. Deoxygenated blood travelling through the lungs has a low O2 partial pressure of around 40mmHg and a CO2 partial pressure of around 46mmHg. Meanwhile, the air in the alveoli has an O2 partial pressure of around 100mmHg and a CO2 partial pressure of around 40mmHg. This causes O2 to diffuse into the blood and CO2 to diffuse into the alveoli. CO2 does not have as steep a diffusion gradient as O2 does (46 - 40 = 6 as opposed to 100 - 40 = 60) but that does get made up for in terms of diffusion coefficent, as we shall soon see.

Membrane thickness

Again, not much needs to be said. The walls of the alveoli are thin (1 cell thick) as are the capillary walls, so the gases don't have to travel far.

Diffusion constant (D)

As mentioned earlier, the diffusion constant D, directly proportional to sol/sqrt(MW), is another key determinant of diffusion capacity. Carbon dioxide and oxygen have somewhat similar molecular weights (40.02 vs. 32), and when you find the square root of those they don't differ by a whole lot (6.3 vs. 5.7). Carbon dioxide is 20x more soluble than oxygen, however, so solubility is probably the main factor determining diffusion constant here. (I'm not entirely sure why carbon dioxide is that much more soluble considering that both molecules are nonpolar overall, but a quick Google search seemed to suggest that the fact that CO2 reacts with water to form carbonic acid may be a part of it.)

Because equations are cool (actually I'm kinda sick of these random equations being thrown out at me here and there, but whatever), here's another one for the diffusing volume of gas per minute which draws on all of the factors above:

Vgas (is directly proportional to) A/T x D(P1 - P2)

Vgas is the diffusing volume of gas per minute
A is the surface area
T is membrane thickness
D is diffusion constant
P1 - P2 represents the partial pressure difference

Describe alveolar & systemic gas exchange


Alveolar gas exchange is simply the gas exchange between the alveoli and the blood. Here oxygen diffuses into the blood down the partial pressure gradient (100mmHg to 40mmHg) and carbon dioxide diffuses into the alveoli down its partial pressure gradient (46mmHg to 40mmHg).

Systemic gas exchange, on the other hand, is exchange of gas between the blood and the tissues. Since the tissues consume oxygen and release carbon dioxide as a waste product, the partial pressures of these gases in the tissues reflects that of deoxygenated blood entering the lungs (i.e. 40mmHg O2 and 46mmHg CO2). This causes oxygenated blood travelling from the heart to give up its oxygen and take on more carbon dioxide.

Discuss the O2 & CO2 transport in blood


O2 does not dissolve readily in the blood, so only 1.5% of oxygen can travel around the blood this way. Hence it has to find a different way to travel around. O2 does this by hitching a ride on haemoglobin, which is a protein located in red blood cells. It is made up of four subunits- two alpha and two beta. Each contains a haem group (also spelled "heme") which has an iron atom that can bind to oxygen. When oxygen binds, haemoglobin becomes oxyhaemoglobin, which is red. This is why oxygenated blood is red.

CO2 dissolves in blood more readily, but very little CO2 (around 5%) actually travels around as dissolved CO2. A further 5% travels through the blood as a carbamino compound, which is basically where CO2 combines with the terminal amino groups of proteins. This includes the amino groups of haemoglobin. CO2 may not directly compete with oxygen for haemoglobin, as CO2 binds to the amino group while O2 binds to the Fe atom, but the binding of CO2 does decrease haemoglobin's affinity for oxygen. This is known as the Haldane Effect. (I would guess that CO2's binding creates a conformational change which reduces its affinity for oxygen.)

That leaves the remaining 90% of carbon dioxide, which actually travels through the blood as bicarbonate ion, HCO3-. When CO2 reacts with water, the following reaction takes place:

CO2 + H2O <----> H2CO3 <----> HCO3- + H+

(I swear, if I have to type <sub> into the HTML editor again...)

Anyway this reaction would actually occur quite slowly if it wasn't for the help of carbonic anhydrase, an enzyme located in red blood cells which catalyses this reaction. The H+ produced from the reaction doesn't get wasted- it instead binds to haemoglobin, also reducing haemoglobin's affinity for oxygen. HCO3- tends to diffuse out of cells due to the concentration gradient and Cl- diffuses into the cells simultaneously in order to keep the internal charge constant. This is known as the chloride shift.

Describe the O2-Hb dissociation curve

The O2-Hb dissociation curve is essentially a graph showing what percentage of haem groups is bound to oxygen at a given partial pressure of oxygen in the blood. It is sigmoid shaped (i.e. S-shaped) which means that there's a steep bit as well as bits where it kinda plateaus. The steep slope (below around 60mmHg) is where oxygen unloading mostly occurs, because a tiny decrease in oxygen partial pressure can cause a massive decrease in haemoglobin saturation. The plateau bit at the top, on the other hand, promotes oxygen loading.

The O2-Hb dissociation curve can be affected by several different factors:
  • Temperature: higher temperature will shift the curve to the right (higher partial pressure of oxygen needed for the same percentage saturation of haemoglobin, i.e. less affinity for oxygen). I'm guessing that this is because a higher temperature might break the bond between oxygen and haemoglobin? A low temperature will do the opposite.
  • pH: a lower blood pH (i.e. more H+) will shift the curve to the right. This is because, as I said before, H+ binding to haemoglobin reduces its affinity for oxygen. This is known as the Bohr Effect.
  • PCO2: shifts the curve to the right as CO2 reduces haemoglobin's affinity for oxygen.
  • 2, 3- diphosphoglycerate (2, 3-DPG): shifts the curve to the right. 2, 3-DPG is an intermediate in the glycolysis pathway that is found in hypoxic conditions. I'm not sure why it shifts the curve to the right, but it does, and it's quite helpful because obviously hypoxic cells want more oxygen.
Understand the alveolar gas equation

I'm going to go out on a limb here and say that I don't really understand this equation. That's not going to stop me from vomiting out what I think I understand, though.

PAO2 = PIO2 - PACO2/RQ

(Hopefully you can read all of the subscripts within subscripts. I've made the font larger so hopefully that helps.)

PAO2 = alveolar partial pressure of O2
PIO2 = inspired partial pressure of O2 (remember, this is like the atmospheric pressure of O2 but adjusted for humidification of the air as it enters the airways)
PACO2 = alveolar partial pressure of CO2
RQ = respiratory quotient

A quick note on RQ: it's essentially the rate of carbon dioxide output divided by the rate of oxygen uptake. This is mainly determined by diet. The average RQ value is around 0.82. A diet with only carbohydrates will yield an RQ of 1, a diet of only fat will yield an RQ of 0.7 and a diet of only protein will yield an RQ of 0.8.

Anyway, back to the equation. Apparently this equation helps clinicians to determine the source of hypoxemia (low blood oxygen). I rewatched that minute or so of the lecture trying to figure out how, but it seems like the main point that we need to take away is simply that clinicians can compare alveolar partial pressure of oxygen to arterial partial pressure of oxygen. From this, they can determine whether hypoxemia is due to hyperventilation or something else. Another thing she said was that we probably won't have to use this equation too much. Yay!

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