Vivacast 02 – CO2 Transport – Intra-Cranial Pressure – Neonatal Physiology

How is CO₂ transported from tissues to the atmosphere?

CO₂ produced in tissues is transported via blood to the lungs, primarily as bicarbonate ions, dissolved CO₂, and carbamino compounds, and is then exhaled through alveolar ventilation.

CO₂ Journey

CO₂ Content of the blood

• 5% Dissolved in plasma
• 60-65% as Bicarbonate
• 20-25% As Carb-Amino Compounds

Co2 is very soluble, and diffuses down its concentration gradient from mitochondria to plasma, In the plasma, a portion of Co2 is dissolved, a lump binds to haemoglobin and a large portion is shifted into bicarbonate for transport.

Enzyme RBC system

• This reaction occurs spontaneously if Co2 is dissolved in an aqueous solution but quite slowly…
• When you add carbonic anhydrase, which is an abundant and very speedy enzyme located in the red blood cell then this reaction is much more efficient.
  • CO2 + H2O —> Carbonic Anhydrase—> H2CO3. ——-> HCO3- + H+
• This reaction in the RBC is gradient dependent and flows in both directions depending on if the RBC is traversing a capillary bed in the tissues vs the lungs.
• A loose H+ ion can be mischievous, and it is subsequently buffered by Haemoglobin, the RBC maintainins its electrical neutrality (the hco3- knocking around now) by shifting a chloride ion (the Hamburger effect).
• The bicarb is shifted out of the RBC by a membrane bound protein passive facilitating transporter
• This means that the RBC can shift more CO2 into bicarb ( its all about those gradients! ) when the blood finds itself adjacent to a membrane with a paucity of CO2 on the other side then the situation sifts into reverse (the alveolus).

Intra-Cranial Pressure – How do Oxygen and Carbon Dioxide Influence ICP.

• Define Munro-Kellie doctrine
  • The sum of everything in the brain adds up to a volume, add more of one and something else has to go down – but if there is nothing else to eek out pressure will rocket (CSF volume reduces first, then venous blood, then arterial blood…. and disaster)
• Define CPP = MAP – (ICP + CVP)
• Oxygen tension in plasma influences the state of dilation or constriction of cerebral vessels.
  • Low oxygen tension cause vasodilation?
  • High oxygen doesn’t do much to ICP but may yield more oxygen radicals.
• Carbon dioxide tension,
  • High CO2 Tension causes vasodilation, increasing ICP
  • Low CO2 Tension Causes vasoconstriction – used as a rescue to buy time to reduce ICP
• Mechanical Factors
  • Head up positioning in the patient
  • Avoidance of tight tube ties
  • Consider a balanced approach to PEEP as it directly influences central venous pressure
• Pathological Causes
  • Intracranial bleeds
  • Cerebral oedema
  • CSF drainage obstruction
• Drug Factors
  • Analgosedation with propofol diminishes ICP and CMRO2
  • Deep muscle paralysis reduces ICP through mechanical means

Neonatal gasp and umbilical clamping

On exposure to higher o2 environment of ex-utero and taking that first gasp, the lungs :

• The inhalational Gasp exposes the alveoli to oxygen releasing hypoxic pulmonary vasoconstriction.
• The nature of expanding the lungs opens up the vasculature from a mechanical perspective
  • Both of these occurrences reduce the pulmonary vascular resistance, which given the short distance of the capillary pulmonary bed leads to lower PVR than SVR
• This has the effect of reducing right sided ventricular and atrial pressure and as such altering the shunt mechanics that were present in utero, These were :
  • A patent Foramen Ovale, where blood passes from right to left atria
  • A patent Ductus Arteriosus which allows the blood that has made it to the right ventricle and into the pulmonary artery to skip the pulmonary vascular bed via a duct into the aorta
• These mechanics reverse, and given the nature of the PFO as a flap valve, Flow across the atria tends to cease.
• The ductus arteriosus is influenced by cirulating prostaglandins as well as plasma o2 tension – it begins to narrow, but fully obliterates from day 3-14 of life.

The clamping of the umbilical cord leads to further shifts, these are:

• Immediately raises systemic vascular resistance, prior to this, the umbilical arteries opened into the minimally resistant placenta.
• This increase in SVR causes an increase in left atrial and left ventricular pressure, further contributing to this reduction in right to left shunt as the pressure in the left system exceeds the right.

The FRCA physiology viva can range far and wide in its content – we are going to cover the slightly more unexpected stations so you are maximally prepared.

In a nutshell the primary FRCA viva consists of 4×15 minute stations, comprising of generally 3×5 min sub sections each.

The stations are

• Physiology
• Pharmacology
• Physics and Clinical Measurement
• Clinical station

GasGasGas will endeavour to produce plenty of example stations and question sets to help with your revision and preparation!

Other episodes are:

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Podcast Information

Transcript Physiology Viva: CO₂ Transport, ICP, and Neonatal Circulation

Introduction and Episode Overview

00:00-02:00

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Hello, so Tom, this is going to be your Physiology Viva. Now, naturally I have to caveat that I’m not an FRCA examiner. I’m trying to make this as realistic as possible for you, and we’re going to be a bit more brutal on timings with this. And I’m going to try and move you on if you’re waffling. Are you happy with that? I’m happy with that.

Okay, so, Tom, this is your Physiology Viva. Welcome.

Carbon Dioxide Transport from Cell to Atmosphere

02:00-06:30

Summary: Tom explains the three main mechanisms of CO₂ transport in blood and the bicarbonate buffering system.

How is carbon dioxide shifted from a cell to the atmosphere?

So carbon dioxide itself is shifted in several different ways from cellular environment to the atmosphere. It’s always transported in the blood, but in several different ways. Firstly, carbon dioxide itself is soluble in plasma, and this can allow it to be dissolved and then exhaled into the atmosphere from its dissolved form. It can be moved as bicarbonate through the blood as well, and then at the lungs can be metabolised back into carbon dioxide and exhaled in that way. And it’s also transported bound to haemoglobin as carboxyhaemoglobin.

Lovely. And could you talk me through how it is stored as bicarbonate, please?

Yeah, so carbon dioxide itself in the presence of carbonic anhydrase can be converted into bicarbonate ions and water in an aqueous solution. So it’s an equilibrium reaction which is pushed in one direction or other by the presence of carbonic anhydrase molecules. This also acts as a buffering system within the plasma as well.

You might expect a hydrogen ion to be formed in this process. How is that buffered?

Carbonic acid itself is a weak acid, so when carbon dioxide is in the presence of carbonic anhydrase, it forms an H⁺ ion plus the conjugate base of carbonic acid. This is why the presence of carbon dioxide is acidic actually, from this process of dissociation of hydrogen ions from water in order to form carbonic acid.

And where does this hydrogen ion go?

Oh, sorry, let me rephrase that. You’ve described this enzymatic process with carbonic anhydrase and the conversion of CO₂ to a hydrogen ion and its conjugate base HCO₃⁻ bicarbonate. Is this hydrogen ion free or does it bond with something?

It combined with histidine residues on haemoglobin molecules, which is an important part of the buffering system in the plasma.

Lovely. So moving on. How does carbon dioxide, from a solubility perspective, relate to the solubility of oxygen?

Yes, carbon dioxide is much more soluble in an aqueous solution than oxygen, and is therefore transported much more readily as a dissolved substance, although the majority is carried as bicarbonate in the blood.

Factors Influencing Intracranial Pressure

06:30-10:00

Summary: Discussion of how gases and other factors affect intracranial pressure through the Monro-Kellie doctrine.

So we’ve mentioned a couple of gases here, and we’re going to move on to how they influence intracranial pressure. So you’ve mentioned oxygen and carbon dioxide. Could you tell me how they influence intracranial pressure and what other factors may influence intracranial pressure?

Yes. So when thinking about intracranial pressure, the Monro-Kellie doctrine states that the intracranial compartment is a non-expandable space. So pressure is directly related to increases in volume within that space.

There are direct effects of dissolved oxygen and carbon dioxide on the vasculature in the skull. So carbon dioxide – presence of carbon dioxide in the plasma – causes vasodilatation of the cerebral vessels. And because they’re dilating within a fixed space, that leads to an increased intracranial pressure, hence focus on normocarbia in brain injury.

Oxygen tension is also important, so hypoxaemia itself also causes vasodilatation and an increase in intracranial pressure. So, you know, again, expansion of blood vessels within that fixed space.

Within normal physiology, there is autoregulation of blood flow within the brain, thus for over a range of different blood pressures, equal flow is maintained, and intracranial pressure is maintained within fairly tight boundaries. This process can become dysregulated in traumatic brain injury.

So what other mechanical influences exist that influence intracranial pressure?

So mechanical influences that don’t directly affect the intracerebral space may include a restriction of blood flow out of the intracranial cavity – i.e. venous congestion. So, this can be important for us when we’re using ET tube ties or placing central lines, as restricted venous outflow will result in an increase in intracranial pressure. And increased inflow is what we’ve already talked about really with vasodilatation. So, the sort of two sides of the same coin.

Any other factors, or any other drugs that may influence intracranial pressure?

Cerebral oedema itself may increase intracranial pressure. So that can be in response to trauma, it can be in response to hyponatraemia. They’re two common ways that you can have tissue damage and oedema within the intracranial cavity.

In terms of agents that we use in anaesthesia commonly, the induction agents in particular – we need to pay close attention to if we’re considering intracranial pressure.

That’s your five minutes up there. So moving on.

Neonatal Physiological Changes at Birth

10:00-17:00

Summary: Tom explains the transition from foetal to neonatal circulation, including the effects of oxygenation and umbilical cord clamping.

On the topic of oxygenation, what physiological changes occur in the neonate when they’re exposed to the higher oxygen environment of the ex utero world and what occurs when you clamp their umbilical cord?

It’s easy to think about this in relation to the circulation of the foetus initially, and then how that changes at the point of birth. Normally within the foetus we have various mechanisms that shunt the most oxygenated blood into the cerebral circulation. They do this by shunting from right side of the heart to the left without going through the lungs.

Within the foetus there is potent hypoxic vasoconstriction of the pulmonary vessels, which helps increase resistance in the pulmonary vascular bed and contribute to this right to left shunt. This occurs across the foramen ovale between the right and left atria.

At birth, a few things happen at once. When the baby starts to take its first breaths, that hypoxic pulmonary vasoconstriction is strongly inhibited in the presence of atmospheric oxygen, and the vascular resistance in the pulmonary bed reduces massively. This means that the pressure gradient across the right and left atria reverses. The foramen ovale, which is structurally essentially a flap valve, closes without necessarily sealing, but the pressure keeps that – like I say, a flap valve – closed.

Blood begins to move in much higher volumes from the right ventricle into the pulmonary tree and is oxygenated and moves into the left atrium and then into the systemic circulation in the way we’re familiar with in adults.

Are you able to repeat the question as well, just so I can be clear exactly what you’re looking for?

Yes, that’s fine. On the topic of oxygenation, what physiological changes occur when A) there’s a presence of a higher oxygen environment, ex utero, and B) when the umbilical cord is clamped?

Ah, and you asked about the clamping of the umbilical cord as well. So when the umbilical cord is clamped, we have immediate reduction or cessation of placental blood flow to the foetus. And we also have reduced venous return from the foetus to placenta as well. Essentially, we have constricted the circulating volume, and as a result, we’ve increased the peripheral vascular resistance for the foetus. So that leads to a rise in the blood pressure of the foetus. And also, that increase in pressure allows for increased oxygen delivery throughout the systemic circulation.

And how does that increase in peripheral vascular resistance relate to the pressure in the left ventricle versus the right ventricle?

So yeah, as we were talking about before, there is a reversal of the pressure gradient between the left and right ventricle, and that increase in pressure from the reduction in peripheral volume and increase in peripheral vascular resistance contributes to that reversal of right to left shunt to a normal circulation.

And where is the ductus arteriosus?

The ductus arteriosus sits itself between the pulmonary artery and the arch of the aorta, allowing for right to left shunting of blood away from the pulmonary circulation in the foetus.

What influences the closure of ductus arteriosus?

So, ductus arteriosus itself closes in response to endogenous prostaglandin release…

And we’ll stop you there.

Post-Viva Discussion and Feedback

17:00-25:00

Summary: Tom and James discuss the viva performance with detailed feedback on answering techniques and key physiological concepts.

So, Tom, how did you feel that went from a physiology viva perspective?

It felt okay, but on this particular question I found myself trying to simultaneously figure out what was required from the question whilst having to speak. And I tripped over myself a little bit and I think was a little bit circular in places because as soon as you come onto the foetal circulation, it feels like quite a big topic. There are quite a lot of things to say, there are quite a lot of facts that we might have picked up at various points in revision. But I was trying to stay focused on the question and not start getting into things that weren’t asked for. But yeah, that caused me to hesitate a little bit and be a bit less fluid than I would have liked.

Answering the Question Asked

Yeah, I think you’ve brought up quite an important point there – that you have to answer the question that is asked of you. So when we went on to the neonatal circulation, you told me some stuff about in utero neonatal circulation, despite the fact that that’s not the question I asked you.

If you’re trying to demonstrate that you have an idea about the neonatal circulation, do it in 10 seconds. I think you spent about a minute describing what in utero was when really I was asking you what happens ex utero – i.e., that first breath and what changes occur. So you might have found yourself losing opportunities to get points by answering the question you thought was asked.

But it’s good that you then went back and actually re-asked what the question was. That’s absolutely fair game, and you might think it costs you time in your five minutes, but if you’ve meandered off piste, taking that opportunity to refocus might get you back into pass territory.

Yeah, and just on the grapevine, you do hear that examiners are generally quite good at redirecting you if you’re going down a rabbit hole, but there is some variability there. Some people don’t interrupt you quite as brutally and you can waste a bit more time, and having ways to refocus yourself, I suppose, can be helpful in some situations.

Key Points for CO₂ Transport

Just in terms of key points we were hoping for across that, when we were talking about the journey carbon dioxide takes from cell to atmosphere. The key words would be: it’s highly soluble, so it moves across membranes very quickly with diffusion.

The reaction that takes place is H₂O and CO₂ via carbonic anhydrase, which is a very, very active enzyme, into H₂CO₃, which then dissociates into a hydrogen ion and HCO₃⁻ bicarbonate, and that hydrogen ion gets neatly mopped up by haemoglobin so that it’s not pottering around causing bother.

Also, it is important to consider the respective amounts of CO₂ transported between these methods, and also carbamino compounds:

• About 5% of CO₂ is dissolved and transported in plasma
• 60% to 65% is transported as bicarbonate through that enzyme system described
• 20% or so is transported directly bound to haemoglobin as carbamohaemoglobin or carbamino compounds

Yeah, and I suppose another thing to reflect on there – it’s a topic that I felt that I knew, but then, in the pressure of the moment, I made a conscious decision not to commit to starting to describe the chemical reactions because I thought I might get it wrong and trip myself up. So I suppose you sometimes face those decision points and in an ideal world it’s on the tip of your tongue and you know it well. But yeah, I didn’t want to start tripping myself up by saying the wrong things.

Yeah, and that’s definitely a balancing act. Because it could have been that actually that was the key element that they want out of you. And I imagine if that is the case, they might start pushing back and trying to get you to commit as opposed to letting you dance around the edges, and I think that’s examiner-dependent.

Intracranial Pressure Concepts

And then the last point: we were looking at cerebral perfusion pressure. And it might have been my wording of the question that made it a bit awkward.

Yes, just to comment here, I’ve had this exact question – practised with a consultant at work actually, and I think they used very similar wording to you. And I think I tripped myself up in the same way because cerebral perfusion pressure itself doesn’t affect intracranial pressure, at least not in the way I think about it. So I was trying to answer the question and not start saying things that you didn’t want to know about.

I thought they’re not asking about cerebral perfusion pressure because I would naturally wait for a more clinical line of questioning to say “and what things can we use to control cerebral blood flow” or something along those lines. Because while we were in the viva, I was thinking about cerebral perfusion pressure, but I made perhaps the wrong conscious decision not to go down that way because I didn’t think that’s what was being asked.

In my head, I think it was intracranial pressure I was going for. But the crux would be: if we were going down the intracranial pressure route, you could say very quickly:

• Carbon dioxide tension causes proportional vasodilatation
• Low oxygen tension leads to vasoconstriction
• There are ways that we clinically alter this with drugs and positioning
• This is all derived from the Monro-Kellie doctrine

I think it’s like I say, I’ve fallen into the same trap before, so I don’t think it’s the way you were wording it, but I guess it’s just a lesson in not tripping yourself up as well. And if there’s a core topic that seems relevant, so long as you don’t spend too much time, if you can, within five seconds, state “cerebral perfusion pressure, which is the difference between the mean arterial pressure and the intracranial pressure, dictates blood flow and oxygen supply within the brain” – that took no time at all. If they’re not after it, they can move you on.

Exactly. If you spend a minute and a half doing that, then you’ve not really hedged your bets if you’re not sure what they’re after. So, yeah, a technique point again, I guess.

And we’ll stop it there, Tom.

Closing

25:00-25:30

If you found it useful or awful, please like and subscribe and rate the show. Definitely check out the show notes for those diagrams and the detail of this content. It is a bucket of content to get to grips with. Keep working at it and you will get better faster and stronger. It is vital to keep your interest alive for the science that we’re covering and not overcook yourself. You will be amazed by what you know come exam day. Don’t freak out, keep studying.

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