VivaCast 6 – Alveolar Gases, Oxygen Cascade, Partial Pressure Sensing and the Valsalva Manoeuvre

What Is the Alveolar Gas Equation

The Alveolar Gas Equation calculates the amount of oxygen as a fraction of the total pressure that ends up in the alveolus. Bearing in mind that there are other gasses and vapours vying for that ‘space’. Resp quotient =0.8 conventionally, and relates to the amount of CO₂ produced relative to oxygen consumed and is influenced by diet.

P_AO₂ = P_iO₂ – (P_aCO₂ / Resp quotient)

P_i0₂= FiO₂ x (Pressure atm – Partial Pressure H₂O)

These are :
Partial Pressure of water vapour Alveolar absolute humidity is 100% . The SVP of H20 at 37DegC at sea level is 6.3kPa of partial pressure
Partial Pressure of exhaled CO₂ – Alveolar CO₂ content in kPa (assumed to equilibrate from arterial CO₂)

All Together in Plain Text

Alveolar O₂ fraction = (Atmospheric O₂ fraction x (Atmospheric pressure –partial pressure exerted by full humidification) – (Arterial CO₂ / Resp Quotient

All Together in Formulaic terms

P_AO₂ = FiO₂ x (P_atm– P_H2O)- (P_aCO₂ / Resp quotient)

If a patients arterial CO₂ goes up then there is more CO₂ displacing oxygen from the alveolus, and thus the potential oxygen content of the alveolus will drop.

What is Partial Pressure?

Assume a max total pressure of 100KPa to work with – in this mix you have Nitrogen, Oxygen, Carbon Dioxide, and Water with a bit or Argon lurking in there, then all these components make up the total pressure, if you have 21% Oxygen concentration then 21KPa of the total pressure is exerted by the Oxygen. The Partial pressure of oxygen in this situation is 21KPa.

Oxygen Cascade

This reflects the diminshing partial pressure of oxygen as it diffuses from atmosphere to its ‘effect site’ in the mitochondria.

Note pressure at sea level = 101.3kPa

In order:

21 kPa Atmospheric partial pressure of o2 : 21×101.3kPa = 21.2 KPa… (21….)
20 kPa Fully Humidified Atmospheric Gases = 21 x (101.3-6.3) at 37degC. = 20kPa
15 kPa The above, mixed with deadspace gases = 15kPa (partial pressure of 02)
13.8 kPa Mixed with Alveolar Gas = 13.8kPa (Alveolar Gas Equation)
13.5 kPa Transition Alveolus into Blood = A-a (Alveolar-Arterial Gradient) 13.5Kpa
6-7 kPa Capillary PO₂
1-2. kPa. Mitochondria PO₂

Note that there is mixing in the pulmonary venous circulation (well oxygenated blood) occurs as it journeys back to the left side of the heart – note that V:Q mismatch (shunts or deadspace) alters the O₂ content as well as mixing with deoxygenated blood from:

• The bronchial veins (blood supply to the lung parenchyma originating from aorta)
• Thebesian veins myocardial veins draining into all 4 cardiac chambers,
• VQ mismatches yielding incomplete oxygenation

Others

• Intra-cardiac R>L shunt,
• Pulmonary AVMs,
• Hepatopulmonary weirdness also

The Pastuer point = 0.3 Kpa – the point at which a mitochondria will not be able to achieve oxidative phosphorylation (1mmhg)

The Shunt Equation

Shunt is: Blood entering the systemic circulation that has not been oxygenated

Shunt is described as a fraction of ‘blue blood vs total cardiac output’

Equation = [math] Q_{s}/Q_{t} = (C_{c}O_{2}-C_{a}O_{2})/(C_{c}O_{2} – C_{v}O_{2}) [/math]

Shunt Flow/Total Flow = ( pulmonary end Capillary content of O₂ – Arterial Blood o2 content) / (pulmonary end Capillary content of 02 – Venous mixed content of O₂)

Q = flow

Pulmonary end Capillary content of O₂ considered equal to the Alveolar O₂ content a la alveolar gas equation

First part of this formula shows the amount not taken up by the blood as it passes a lovely O₂ full alveolus – in normal land an Alveolar/Arterial gradient sort of amount

Second chunk of this formula show the amount of O₂ that could of been taken by blood corssing the alveolus vs the measured venous O₂ content of the pulmonary Artery (ie before it crosses the alveolus)

In practice – identifying shunt involves administering 100% O₂ and seeing if the patients SPO₂ improves. In more scientific manners you would need to be thinking about Pulmonary artery blood sampling and putting a number on cardiac output.

If it does not improve, and their PaO₂etc remains relatively static then you starting thinking about the potential for a significant shunt causing bother.

HPPV

A reflex mechanism in the vascular bed of the lung, that delivers vasoconstriction in response to reduced oxygen tension in the alveolus – leading to a better match in blood flow to oxygen availability as blood is pushed towards areas that are not vaso constricted.

Widespread alveolar hypoxia will increase the pulmonary vascular resistance and cause right heart strain (sleep apnoea, altitude, hypoxic gas mixtures)

If you were to abolish/impair HPPV (think volatiles, nifedipine) then you will cause a shunt.

This is why anaesthetised patients sometimes have worsened oxygenation,

NITRIC OXIDE –

ORAL VASODILATORS INJ pHTN?

Partial Pressure Plasma Sensing

Peripherally:

nb – Doxapram acts on these peripheral chemoceptors.

Carotid Body – CNIX

P_AO₂ / P_ACO₂ and pH changes
Respond to partial pressure as opposed to oxygen content hence, anaemia will not trigger increased RR through this mechanism

Aortic Body – CNX

P_AO₂ reductions and P_ACO₂ increases

inverse modulation, so if oxygen’s low,. then the response to CO₂ is sensitised and vice versa if CO₂ climbs then there is increasing sensitivity to oxygen changes

Centrally

In Ventral Medulla – hydrogen ion sensing
CO₂ diffuses across BBB and disasscoiates in CSF and the concentration of this is detected. There are fewer buffering compounds in the CSF and therefore pH shifts happen more readily.

This influences the respiratory centres driving changes in ventilation.

It takes a while for Plasma Hypercarbia compensation to equilibrate with CSF (shift of bicarb into CSF space).

Valsalva Manoeuvre

Forced Expiration against a closed glottis aiming for a 40mmhg increase or so (54 cmH₂O)

Broken down into 4 phases.

Stage – 1

• Increased intra thoracic pressure causes
• Elevation in BP as lung blood squeezed towards heart

Stage – 2

• Pressure remains high
• The held pressure impairs venous return to heart
• Reflexive vasoconstriction and a tachycardia counter
• Maintaining a sensible BP ( baroreceptor and SNS mediated)

Stage – 3

• ‘Release’ drop in intra thoracic pressure
• Central Venous and Lung capacitance increases, they ‘refill’
• Blood flow to heart drops off
• Blood Pressure Drops as not much flow as everything refills
• Further reflexive activity to counter
  

Stage – 4

• Intra thoracic Pressure normalises
• Vasoconstrictive reflex is ongoing at this point
• Now everything has refilled
• Forward flow resumes at normal rate
• Thus cardiac output is into a vasoconstricted circulation > increased BP = reflexive bradycardia triggered

We Debriefed here and drew a few conclusions.

Sometimes the most critical thing is getting to the point of the question.

We explored the above concepts and certainly challenged Tom to get sharper on his delivery and get to the point.

In a valsalva manoeuvre question, you could say – the ultimate outcome of this is a reflexive drop in heart rate secondary to a raised blood pressure. Doing so demonstrates you know the craic, and then you can elaborate on how the mechanism goes about its business.

If you start waffling about factors – the examiner will immediately catch the anaerobic whiff of despair even if you know the content overall, don’t give them the pleasure!

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“Thanks for listening guys… Every day you are getting better at this. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying!”

Podcast Information

Transcript Oxygen Transport and the Alveolar Gas Equation

Introduction

[00:00 – 01:15]

Hello and welcome to Gas, Gas, Gas, the podcast that covers the FRCA primary exam. We’re going to fit into your day and give you as much of your life back as you could possibly imagine. I’m here to make your studying easier. Listen to us on your commute, in the gym, in the shower, or when you’re ironing your scrubs. Expect facts, concepts, model answers and the odd tangent. Check out the show notes for all the detail, and remember to follow the show so that you never miss an episode. Let’s get on with it.

Alveolar Oxygen Content and the Alveolar Gas Equation

[01:15 – 05:30]

Summary: Discussion of factors governing alveolar oxygen content, the alveolar gas equation, and the importance of stating equations promptly in examination settings.

So hello Tom, welcome to your Physiology Viva. What factors govern the oxygen content of the alveolus?

So the oxygen content of the alveolus can be thought of in relation to the gas exchange in the alveolus and some changes that occur on its way there. The atmospheric concentration and partial pressure of gas is initially important. In an environment with 100% oxygen, you’ll have a much higher percentage reaching the alveolus. In a typical situation with 0.21 fraction of inspired O₂, we have an initial reduction in the concentration of oxygen as air is warmed and humidified in the upper airways. As the gas descends from the nasal passages and the oropharynx, it mixes with exhaled air from the previous respiratory cycle sitting in the upper airways. This then further reduces the concentration of oxygen in that mixed gas, which now contains CO₂ at a much higher concentration. Moving further down towards the alveolus, humidification also increases further, and we have that final concentration in the alveolus that’s dictated by those things. So atmospheric concentration of oxygen, humidification within the airways and mixture with expired gases.

Lovely. And is there an equation that unifies all these things?

Yeah, the alveolar gas equation unifies all of these things. The alveolar gas equation will allow you to calculate oxygen concentration within the alveolus by relating it to respiratory quotient and the end-tidal CO₂ content and arterial CO₂ content. The alveolar gas equation will allow you to calculate alveolar concentration of oxygen by relating the fraction of inspired oxygen to the…

Hey there, Tom. You need to be much quicker at getting the equations out. I don’t want to hear how they all relate to one another, because the equation will tell me that. If you start prevaricating, then the examiner’s going to smell a rat. So you’ve just got to get the equation out into the open so that the examiner thinks, right, okay, I can move on, yeah, they know it.

Oh, okay, I thought I was describing the wrong equation.

Anyway, you’ve got the concept there, but you lost time.

Need to be quicker. I couldn’t remember. I was trying to remember the concept while I gave myself a chance to remember the constituents.

So PₐO₂ equals the fraction of inspired oxygen times by the amount of humidified air as a partial pressure knocked off your atmospheric pressure minus the PₐCO₂, so the arterial CO₂ content divided by the respiratory quotient.

It’s one of those that’s definitely easier to write down.

100%. Yeah.

Oxygen Cascade: From Alveolus to Mitochondria

[05:30 – 07:45]

Summary: Comparison of oxygen partial pressures from alveolus to mitochondria, explaining the oxygen cascade and diffusion barriers.

And how does this alveolar oxygen content compare to mitochondrial oxygen content?

Alveolar oxygen content is significantly higher than mitochondrial oxygen content because gas needs to diffuse first of all across the alveolus, which in normal physiology it will equilibrate. And PₐO₂ is a very close approximation of alveolar oxygen. But beyond that point, in order to reach the mitochondria, oxygen has to diffuse across endothelial walls via the interstitial fluid into the intracellular fluid and then to the mitochondria itself. So whilst it’s carried very efficiently bound to haemoglobin in blood, the amount of dissolved oxygen that can reach the mitochondria is significantly lower than the concentration found in blood.

Could you hazard a number on that?

I believe it’s 1.4 kilopascals at the mitochondria. So compared to concentration in air, which is about 21 kilopascals.

The Alveolar-Arterial Oxygen Gradient and Shunting

[07:45 – 12:20]

Summary: Explanation of the A-a gradient, physiological and pathological shunts, including classification of different shunt types.

So, why is there a difference in P(A)O₂ (alveolar) and PₐO₂ (arterial oxygen content)?

In normal physiology there is a difference between those two due to physiological shunting via veins within the lung itself and via the thebesian veins draining directly into the left atrium from the heart. So those small amounts of blood are not oxygenated before they reach the systemic circulation.

Okay. Could you classify these different types of shunt in a bit more detail for me?

Shunt is essentially a concept of a proportion of blood that reaches the systemic circulation without being oxygenated in the lungs. We’ve already mentioned physiological shunting, which happens in normal physiology. We have various types of pathological shunts. We can have right to left shunts in the heart, such as with atrial septal defects or ventricular septal defects, and that leads blood to pass without going through the pulmonary vascular bed and therefore not being oxygenated. We can have shunt because large areas of the lung aren’t perfused, such as in pulmonary embolus – an obstructive type of shunting. And we can have areas of the lung that are not at all ventilated and therefore blood can be shunted from right to left side of the circulation without being oxygenated via that process, such as in pneumonia.

Hypoxic Pulmonary Vasoconstriction

[12:20 – 16:45]

Summary: Mechanism of hypoxic pulmonary vasoconstriction as a compensatory response to poor ventilation, including pathological consequences and pharmacological considerations.

And are there any pulmonary mechanisms that could counter this poorly ventilated alveolus that you mentioned?

Yes, so we’ve evolved a mechanism for making oxygen absorption more efficient in situations where areas of the lung are not oxygenated, namely hypoxic pulmonary vasoconstriction. There is a direct effect of partial pressure of oxygen within the interstitial fluid of the lungs on the small vessels of the lungs, such that the lower the partial pressure of oxygen, the higher the tone in smooth muscle – higher levels of vasoconstriction. This in effect reduces the flow to those areas of lungs with low partial pressures of oxygen, and the blood instead is shunted elsewhere into the vascular bed of the lungs, normally to better ventilated areas of the lungs where oxygen uptake is more efficient. In some pathophysiological states though, there can be problems with this mechanism as well. And if the entire lung is suffering from low partial pressure of oxygen, this can actually be a harmful mechanism rather than a helpful one.

Just out of curiosity, you mentioned harmful. How so?

In lung disease that leads to globally reduced partial pressure of oxygen in the interstitial tissues, you get hypoxic pulmonary vasoconstriction in the entire vascular bed, leading to pulmonary hypertension. This can also lead to right heart failure. A classic example would be cor pulmonale in patients with chronic obstructive pulmonary disease.

Excellent. So you mentioned some pathological things that are somewhat incompatible with hypoxic pulmonary vasoconstriction. Are there any pharmacological agents you know of that alter these mechanisms?

Yes. Inhaled nitric oxide can be used as a pulmonary vasodilator, and this can be used in some critically unwell patients with right heart failure and pulmonary hypertension. There are other pharmacological agents that can be used in chronic pulmonary hypertension orally in order to vasodilate the pulmonary vascular bed, usually prescribed under the direction of a cardiologist, which includes… I can’t recall the names of the oral agents actually. We also see dilation of the pulmonary vascular bed when we administer volatile agents in anaesthesia, which does cause some extent of V/Q mismatch even in healthy patients, which can go to explain the required high fraction of inspired oxygen needed to maintain normal saturations even in healthy patients.

Oxygen and Carbon Dioxide Sensing Mechanisms

[16:45 – 22:30]

Summary: Discussion of peripheral and central chemoreceptors for oxygen and CO₂ sensing, including carotid bodies, carotid sinus, and central respiratory centres.

Lovely. So HPV is clearly a local oxygen sensing apparatus for managing oxygenation on a tissue level. What other sensing apparatus are present in the human for oxygen and CO₂ levels in the plasma?

So I’ll begin with oxygen sensing within the plasma. The partial pressure of oxygen in blood is sensed by specialised cells within the carotid bodies, and this via links to the central nervous system can directly modulate respiratory drive. In terms of… just repeat the wording of the question again, you wanted to know about CO₂, but did you say specifically?

Just oxygen and CO₂ sensing apparatus for the plasma in the body.

For the plasma in the body. So, the reason I asked again was just to be clear about the plasma part. For sensing CO₂ content in plasma, there’s no direct mechanism. However, H⁺ ion concentration is proportional to carbon dioxide partial pressure within plasma because carbon dioxide readily dissociates into carbonic acid and creates water and H⁺ ions. Carbon dioxide itself can freely cross the blood-brain barrier and reach the interstitium of the brain tissues. At that point, when carbonic acid is formed and H⁺ ions alongside it, those H⁺ ions are sensed centrally and directly modulate respiratory drive via the respiratory centres in the medulla oblongata.

Lovely. Try to keep things on topic. We have a carotid body and we have a carotid sinus. What sensing mechanisms are present in the carotid sinus?

The carotid sinus contains baroreceptors that respond directly to blood pressure and create increasing neuronal outflow in response to lower blood pressure.

Clinical Applications: Carotid Massage and Valsalva Manoeuvre

[22:30 – 28:15]

Summary: Clinical manoeuvres utilising cardiovascular reflexes, including carotid massage for SVT and the Valsalva manoeuvre with its haemodynamic phases and application in autonomic testing.

Are you aware of any sort of manoeuvres we can use to manipulate this mechanism to our benefit as physicians?

By conducting carotid sinus massage, we can induce increased parasympathetic outflow in order to try and lower heart rate. This can be particularly useful in supraventricular tachycardias as an initial technique.

Yes, and if your carotid sinus massage might fail in a patient with a supraventricular tachycardia, what other manoeuvre might you consider?

Valsalva manoeuvre.

That’s brilliant. And could you describe the haemodynamics of that?

The Valsalva manoeuvre… I’m sure I won’t be able to go into as much detail as the examiner would like, but essentially, it’s a forced expiration against a closed glottis. So you get a sharp rise in intrathoracic pressure that causes a sharp rise in blood pressure initially. And then over a prolonged period, you get this decreased venous return to the heart, and with that you get a decreased cardiac output, and then over a prolonged period you get a drop in blood pressure despite still exerting that high intrathoracic pressure. Upon release of that high intrathoracic pressure, you get a sharp drop in blood pressure before that increased venous return reaches the heart and causes cardiac output to go back to baseline. And the body has to respond quickly to those changes in blood pressure, hence the reason that patients with autonomic dysfunction cannot correctly respond to these changes in blood pressure.

Just briefly, to interrupt on that. So what I’m looking for when you’re talking about the Valsalva manoeuvre is, can we relate intrathoracic pressure to venous return and what that means for blood pressure? And you’ve done that. And it is quite a convoluted answer because it is quite a convoluted topic. But as long as you’ve got your through line from intrathoracic pressure to venous return to cardiac output to compensatory mechanisms, you can demonstrate that you’ve got the concept of what’s going on. You can then give the details as you’ve got time. So I’d probably be more brutal in your answer and be like: So the Valsalva manoeuvre increases intrathoracic pressure, and the initial effect, because you’re increasing the pressure on the thoracic aorta, is that you’re going to cause a transient rise in blood pressure. At the same time, you’re affecting venous return. The increase in intrathoracic pressure decreases venous return, so the blood pressure actually starts falling, and compensatory mechanisms like tachycardia and increased systemic vascular resistance come into play. And then when you stop doing a Valsalva manoeuvre, the intrathoracic pressure drops, the venous return returns to normal. There’s a transient drop in blood pressure because you’ve lost that squeeze on the aorta.

And there’s an overshoot in blood pressure. Excellent.

That’s all that waffle is just so you can get there and be like: and there’s an overshoot in blood pressure.

Excellent. And how would this bear out in a patient with significant autonomic neuropathy?

Patients with significant autonomic neuropathy, such as spinal injury patients or diabetic patients in some cases, will show an inability to respond to the changes in blood pressure as described in the Valsalva manoeuvre, so their blood pressure will drop more significantly initially and they won’t then overshoot and develop hypertension or bradycardia at the end.

Excellent. Lovely. And that is the end of your physiology viva.

Post-Viva Discussion and Learning Points

[28:15 – 35:00]

Summary: Reflection on examination technique, knowledge gaps identified, and teaching points regarding carotid body chemoreceptors and equation presentation.

Thank goodness for that.

How did you feel about all those questions? We did the alveolar gas equation and then we explored shunting, hypoxic pulmonary vasoconstriction, oxygen sensing, CO₂ sensing, and then Valsalva manoeuvre.

Okay, I think sums it up. Okay, but I think equations – there are a few of them that I think I need to be a bit quicker at having on the tip of my tongue. Or I think it does actually help to write these things down. I think it’s a good technique in the exam because it can be quickly inspected and recognised to be correct. It takes a very long time to say the alveolar gas equation out loud, and it’s quite easy to say one part of it incorrectly. And a sharp examiner will pull you up.

Yeah, and it means that you can spend less time demonstrating that you know what the answer is.

The other areas – I think it can be difficult to know how much depth to go into sometimes. Again, I think we’ve talked about this before, but general exam technique: I’m trying to begin with broad strokes and allow the examiner to focus me. It can be easy to lean towards things that you know rather than answering the question sometimes.

Yes, I noticed that you mentioned telling me about central nervous system CO₂ sensing when I just asked you about the plasma.

Yes. So I think that’s a knowledge gap. I asked you to repeat the question, didn’t I? And when you said “in plasma” I was thinking that it was all centrally sensed. But is there – do the carotid bodies contain pH sensitive cells?

I do believe they do. Yeah.

I wondered if they did, but I honestly wasn’t confident, so I didn’t commit myself to saying it. So that’s the learning point for me then. Do you have any more detail about CO₂ sensing in the carotid bodies? Is it direct sensing of CO₂ rather than H⁺ ions? I think that rings a bell.

Yeah. Yeah, it doesn’t do any of the clever stuff that you would talk about.

It’s the partial pressure of CO₂ and an increase there increases respiratory drive.

Yeah, your carotid body does PO₂ and PCO₂. The sinus does pressure, doesn’t it? And then there’s also stuff in the aortic body.

Yeah, so you asked in the question, I think, about aortic body… oh no, you didn’t ask about… you asked about carotid sinus versus carotid bodies. And my memory started failing me there again as well. So carotid body compared to the carotid sinus: in the carotid sinus you have baroreceptors and in the carotid body that’s where you have your chemoreceptors for oxygen and PCO₂.

I imagine in the exam I wasn’t going to ask you to do it over the audio. They might want you to describe the shunt equation.

Yeah, so as soon as you start talking about shunts I started scrambling in my head for the shunt equation, and if I’d have been confident, I probably would have stated it.

It’s a big one.

Yeah, that’s the thing. Especially without writing it down, I think it would have been a mess.

Yeah.

It’s going to be in the show notes, no doubt, James.

It will be in the show notes. But I do have a clinical question, depending on how much energy you’ve got, and if you want a clinical question or not.

I’m fine, I think I’m doing a bit better than you at this point.

Yeah, it’s been a long day.

Hard work having to listen to me go on about primary stuff.

Yeah, and having to pay attention and be like, shit I should have checked this. It’s actually quite hard to write viva questions because you end up writing an essay as an answer that you’re looking for. Even when I’ve used books and stuff, you can’t just have a load of pages up, and it’s not easy.

Anyway, I’m complaining.

Closing and Preview

[35:00 – 36:30]

Are you ready for your clinical viva, Tom?

Ready as I’ll ever be.

You’re on call and you’ve been asked to see a patient with bowel obstruction and a perforation. Naturally, everyone, time is not linear in Gasland. And therefore, if you do want to hear about Tom’s delightful excitement into his emergency laparotomy clinical station, feel free to listen to the last episode. 

Anyway, thanks for listening. See you next time for more Vivocast fun. It’s pharmacology time, and Tom’s doing adrenaline receptors – the lucky sausage. Thanks for listening to the episode, guys. If you found it useful or awful, please like and subscribe and rate the show.

Definitely, go check out the show notes on gasgasgas.uk. We all know that this is a bucket of content. I want you to take some time for yourself and don’t overcook it. Don’t freak out, keep studying.

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