Hypertrophy (Skeletal, Cardiac, and Smooth)
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Welcome everybody to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Todorovic, and I'm joined by my co-host, Chris Evans. Oh my God, Chris Evans, everybody. Woo! How are you, Chris? Why is our noses not 12 inches long? Oh, why? Well, then it would be a foot. Oh, not bad. Not bad at all. Are they getting better, do you think?

They have their moments. They do. Matt, how are you? So that would actually be maybe nasal hypertrophy. Hey, nice going. Linking it back to the topic. Very good. Hypertrophy is the topic of today. One of the reasons why we're doing this topic is I did a podcast. I was invited. Oh, was it a podcast? I was invited by- The world's strongest, Australia's strongest man. No. What?

Well, I think he has some Australian strongman records actually. So I was asked by a friend of mine, a friend of ours, Sebastian Oreb, who's Australian strength coach. That's what he is online. He is a very strong man and he trains some of the strongest people in the world. He's the strength coach for the mountain, for the world's strongest man, Thor Bjornsson. Is he still the strongest man?

I think he's gone back into strongman competitions. Whether he's the world's strongest man at the moment, not too sure. But he's still bloody strong. We went to his gym, not Thor's, but Bass's gym, which is in Sydney, when we were on the set for the TV show. Limitless with Hemsworth. Hemsworth, yeah. So we had a free half day. Well, we were actually doing in the Hemsworth...

Movie, TV? Yeah. I should really know that, shouldn't I? We're doing real-time analyses of heart rate, breathing. He was wearing an exercise vest that gave us certain...

physical physiology recordings in the movie that is. But we took the same or one of the same vests to Bas's gym. Yeah. But we just rocked up and we're like, hey, Bas, would you mind putting this on and do some squats? We just want to see how your blood pressure changes.

Remember how he said, oh, I wasn't training today, but sure. He's like, yeah, yeah, it's not my legs day. But yeah, sure, let's do it. And how much did he end up back squatting? He ended up doing like 300 kilos. It was 300 kilos squat. And it wasn't even backstage.

He wasn't even maxed out. He was like 80%. Isn't that insane? Yeah, crazy. And this guy's not much taller than me. Would you say? Maybe a bit taller than me? Maybe 12 foot taller than me? A little bit taller but not by much. But you look at him and you go, that's a strong man, right? That's a thick man. And yeah, so I had a chat with Bas and some of his clients who are strength coaches themselves and PTs.

who we sort of helps trains and mentors all things strength training. And so we had a chat about hypertrophy, skeletal muscle hypertrophy, getting larger muscles, right?

And what are the biological processes that contribute to it? What are the molecular mechanisms? How does it all work and so forth? So he went from the perspective of a coach talking about, you know, reps, sets, volume overall, resistance training and the specifics. And I spoke about the biological and the molecular mechanisms that underpin. And I thought, you know, it was a really interesting conversation with Bass about

Maybe we could try and recapture it. Obviously, it's going to be more boring because Bas isn't here and it's you instead. But I thought we could have a chat about hypertrophy. What do you think? Let's go. Now, I think we need to begin. Do you have a definition of hypertrophy? If not, I do. Well, hyper increase, trophy increase.

Growth, isn't it? Growth. Yeah. To nourish. Increase growth. So effectively, because there's two terms that a lot of people use interchangeably but they're different, which is hypertrophy and hyperplasia. So hyper means greater than. It's some increase. Yep.

But hypertrophy generally is an increase in the size of something and hyperplasia is an increase in the number of something, right? That's right. So these would fit under the category of cell or tissue adaptation within the body to try to maintain homeostasis. But when your cells are exposed to stresses, they obviously don't want to die because

They want to respond to the stress in a way that they can adapt to overcome it. Yeah. And I think that's a good way of putting it. That's exactly what happens. And so in most tissue...

If you are placing stress upon a tissue or cells or tissue, the ways that they would generally respond is in the two categories that you mentioned. So some cells have the capacity to increase in number. So if they have an increased type of stressor on it, which could be a workload stress, so it's just expected that the tissue needs to increase its output.

That's a workload stress or might be a metabolic stress or it might be a hormonal stimulus. The cells, if they have capacity, they can say, look, I need to improve my efficiency here. I don't have the ability to do this on my own. So what I'll do is I'll just increase the number. Yeah, that's right. Or depending on the...

again the tissue type which we can get to in a second, they may not have the capacity to increase the number, they can only increase their size. Yeah. So an analogy I'm going to use today. Oh, okay. You love my analogies.

You've blindsided me with this analogy. Let's hear it. Can I judge? Can I judge a quality out of 10? All right, 0 to 10. 0 being the worst analogy, 10 being the best. Okay. All right. So the analogy is lawn mowing. Now, you have a new house with a bit of a lawn, right? Yes, I've got thousands of square meters. But a lot of it's garden, so there's not a lot of grass. Okay. All right. Anyway, so...

Michael Todorovic being, let's just say, the sell and he's pushing a lawnmower. A push on? A push lawnmower. Okay. Everyone knows what that means, right? Yeah. I don't explain it. Just a normal lawnmower. So Michael can manage that quite comfortably. Thank you. With the amount of grass he has to cut every week.

But if you were to increase the size of the lawn, let's say go into an acre. Okay. No longer can Michael complete that job with a push lawnmower. Okay. Okay. So for him to complete that task, he could do two things. Yeah. He could increase his number. So just get a whole lot more people with push lawnmowers.

Yes. To mow the lawn. That's true. Or he could probably sensibly in this regard just get a bigger lawnmower. Increase the size of my lawnmower. That's right. And get a ride-on. Hence why they usually get ride-ons. So getting a ride-on is – it sounds rude saying that. Getting a ride-on is hypertrophy and getting more people to mow with me is hyperplasia. That's right. You know what, Matt? What?

That's a solid six out of ten. Okay. That's a solid six. I'll take it. I think that's the highest I've ever given you. No, I've had some good ones recently. But yeah, that...

So just to underscore this physiologically. Oh, you're going to explain it in a third different one. No, no. To increase the number of cells, these are usually tissues that have the ability, it has a stem cell that's mitotically active and it can just up the amount of cells that's popping out. So hyperplasia. Yes, that's hyperplasia. So a good example there would be the… Epithelium. Yeah, epithelium or I was going to give the example of…

bone marrow with blood cells. Yep. You know, if you put stress on it and you're saying... Crikey. Were you going to say crikey? Crikey. We are hypoxic here. Oh, mate. We...

We need more oxygen to be carried. Righto. That's probably going to come from the kidney. You're kidding me. So the kidney is like we're running out of oxygen. We need more red blood cells to carry oxygen. So what I'm going to do is release a hormone called EPO. Oh, my God. You're going a lot of detail with this. EPO goes to the bone marrow and what does it do? Just make more red blood cells. Yeah. So bumps up the production.

But they get bigger, they just increase their number. Okay. Or, you know, like as an example, skin. If you get injured skin, you need to repair it. You increase hyperplasia. Yeah. Now we go to...

certain tissue that doesn't have that stem cell. So we're finally getting to hypertrophy. How many minutes has it been? We haven't even, we're just defining it all. Sorry. That's okay. I'll wait for your fifth analogy. You have some tissue in the body that has no ability to replicate more numbers. Post-mitotic we call them. And one example here are the muscles of the body. And we know that muscles can be broken into three categories. That

That being cardiac. Unlike bones, which are generally broken into two. Well, unless it's comminuted. All right. Shut your mouth. Pieces. Okay. So, skeletal. No, I started with cardiac. Cardiac, heart, smooth, a lot of places, skeletal. All right. Let me explain it because you're explaining like a three-year-old. Skeletal muscle attaches to your bones, crosses joints, allows for conscious movement.

Smooth muscle lines your hollow organs like your digestive tract, your reproductive system, renal system helps push substances through and your cardiac muscle is the muscle that comprises of your heart and when it contracts, it allows for blood to be pushed under pressure.

So the thing that muscles have in common is they have the ability to shorten. That shortening produces a force and that force produces an outcome. For skeletal, it's physical movement. For heart, it's pressure for blood. For smooth muscle, it's enough force behind to push substances through. That's pretty good, don't you think? Pretty solid. So when we think about hypertrophy...

You said very nicely that it happens in result as a result from a stressor, right? And so it can happen and the result of hypertrophy might be beneficial to the organism to help next time that stressor, the body's exposed to that stressor, the change might be enough to

not have any negative issues from that stressor or maybe the change trying to help is detrimental and becomes pathological yes right would generally be broken into physiological compensation or pathological compensation right so with skeletal muscle generally speaking skeletal muscle hypertrophy which was probably going to be the focus of today is beneficial hypertrophy right yeah in in

uh exposure to like a physical stress yeah yeah i guess physical stress being often a resistance training until it gets to the point where you know the muscle's so large you can't perform you know why do you keep looking at me daily function yes okay i my biceps don't allow for me to go to the toilet properly and wipe my bum i need to use a rag on a stick okay so um

Generally speaking, the physiological adaption to mechanical stress, the muscle will hypertrophy, which will be a benefit to overcome that demand. All right. So let's get into it. Let's get into it. When we look at the anatomical differences between skeletal muscle, smooth muscle and cardiac muscle, they're all different because of their location. Therefore, they have a slightly different function. Yes, they all shorten and contract and allow for force to be generated, but they're different. One of the key differences out there

excluding just their shape, is their nuclei. Okay. Which I think is probably the most important thing when it comes to skeletal muscle hypertrophy. Their nuclei and also what they're filled with. So, for example, skeletal muscle...

Most of it is filled with contractile subunits, contractile proteins, which we call thin and thick filaments, actinomycin. Can you do like the babushka doll of musculature muscle? No. Do we need to? Yeah, I think so. Go, you do it. No, I think you're better at explaining it.

Oh, I can't even remember. A muscle fiber is a muscle cell, right? Okay, so if you were to... That's the smallest subunit. Now, I'm going to say to Michael, hey, Michael, pick a random muscle in your body and let's do that as an example. And we know straight away he'll just say bicep brachii. So if you were to look at the bicep brachii, which kind of attaches to the scapula and goes down to the forearm...

And you were to look at its bulkier section, which is kind of mid-humorous, would you say? Yeah. Ballpark. And you would slice through it with a knife. Yeah. And so you're looking at the muscle in cross-section. Yeah. You would have the whole muscle bulk, which is the muscle itself. That's the muscle. And then you look inside of that big...

Cylindrical? No, it's not only cylindrical. It is. What depends on the muscle you're talking about? What's the shape where it's kind of got tapered ends? Yeah, tapered. There's a term for it. Okay. It doesn't matter. So, okay. We've got the whole muscle, right? We've got the whole muscle, the whole biceps. Now you're getting excited about it. Before I couldn't motivate you enough. Now all of a sudden you want to do a whole extra round. You take forever to explain something. You've got the biceps, whole muscle, right? Yeah.

that's the skeletal muscle that we always talk about, but it's made up of multiple muscle cells, which we call muscle fibers. They're all held together ultimately by connective tissue, right? The connective tissue that holds it all. The whole muscle together. The whole muscle together is like epimycin, epimycin or fascia, right? Holds the whole thing together. Epi meaning on top.

On top of, yeah. Yes. Now, if you do a cross-section and have a look inside, you'll see that there's bundles, also known as fascicles, that sit within that muscle fiber. If I pulled one of those fascicles... These are like compartments within the muscle itself. If I pulled one of those fascicles out, that's made up of individual muscle cells, which we call the muscle fibers. That's surrounded by perimyceum, more connective tissue. If I pull out a single muscle cell or muscle fiber...

That's surrounded by connective tissue called endomycin. And the muscle fiber is simply just composed of these filaments, which are contractile proteins called thick and thin filaments. But they're kind of categorized in the sarcomeres, which are like almost the compartments of a train. Yeah, it's like that. Like the whole train length. Yeah, if the train could contract. That would be the muscle fiber.

Each kind of carriage would be a sarcomere. That's right. And that's what shortens, is the sarcomere shortens. And if the sarcomere shortens, the muscle fiber shortens. If the muscle fiber shortens, then the fascicle shortens. If the fascicle shortens, then the whole muscle itself shortens and muscles are connected often across two joints and then the joint bends. Now, inside...

Of a skeletal muscle, you've got a lot of nuclei, you've got a lot of mitochondria, you've got a lot of contractile subunits. The majority, like 70%-ish of the internal structure of a skeletal muscle is just contractile proteins. So that's just the actinomycin? That's just actinomycin. And you've got a lot of nuclei. Yeah.

Multi-nucleated because that's where DNA sits. So this is a rarity in cells to have more than one nuclei within a cytoplasm? Yes. So these have got multi, many. Yes, that's right. And why would you need this? Well, inside nuclei is DNA. DNA is the blueprint. We need to transcribe and translate DNA into proteins, including contractile proteins. So if we need to make more contractile proteins, let's say, in response to...

resistance training, it needs to stimulate the nuclei to transcribe and translate these proteins. The more nuclei we have, the more proteins we can make, hence hypertrophy. Yeah. You'd probably just assume without doing resistance training, these contractile units just constantly need to be repaired and fixed up. Yeah. Hence why you've got so many nuclei there. If we compare that to smooth muscle...

There's less contractile subunits. They're not arranged as neatly. So in skeletal muscle, they're arranged in series and in parallel, but they're not arranged perpendicular to each other, which means you don't get – you shorten across the length of the muscle fiber. You don't shorten across the width of the muscle fiber or even perpendicular or oblique. But in smooth muscle, the whole muscle, which is shaped like an eye –

the whole muscle cell, which is shaped like an eye. At least in the biceps case. There are some skeletal muscles that have different orientation of fascicles and so forth. Yes, but that's the fascicle. So if you take the individual muscle cell though, it's still arranged in series. So it will still shorten across one plane, right? But smooth muscle isn't the case. The single muscle cell, the whole muscle cell will basically constrict. It's like a string bag. Yeah, it is like a string bag, which was your nickname in high school. And so...

They're only a uninuclear, one nuclei, right? One nucleus, I should say, since nuclei is plural. And then you've got cardiac muscle cells, probably a little bit in between the two in a way, but more aligned in regards to their contractile units like skeletal muscle, but are still uni, sometimes binuclear cells. And branched. And branched. They kind of do separate.

What's the term? Bifurcate. Yeah, and that branching is important because it allows for one muscle cell to speak to the next and communicate directly, which means when one cardiac muscle cell contracts, all of them contract, and that's called a syncytium. Right. Is it the branching that does that or is that just the gap junctions? It's the gap junctions.

Well, it's the gap junctions that connect each branch to each other. So would the branch be more about giving the heart capacity to be more of a 3D? I know the skeletal muscles are 3D, but you know what I mean? I mean, that's part of it. But I would say another big part of it is the fact that...

It allows for more – so for example, if I wanted to physically communicate with people, I would stretch one arm out to grab you and another arm out to grab somebody else. And then if I could contract, I could pull you both towards me, right? Yeah.

If I wasn't branched, I could only grab hold of you. So I could only align in one series. So you're right about the three-dimensionality of it. But it also allows for I can connect to multiple different cells at once to tell them to do something simultaneously. So it's probably both. So the point we're trying to get across here, or at least I am,

The more nuclei, the greater the capacity to create more contractile subunits. Skeletal muscle has the greatest capacity to do this. So skeletal muscle has the greatest capacity for hypertrophy. It doesn't mean the others can't hypertrophy, but skeletal muscle has the greatest capacity to do so. And they do hypertrophy, but not to the extent. What's correct? To hypertrophy or to hypertrophy?

You're asking the wrong person. Oh, that's for sure. All right. So what now? All right. When it comes to... We'll start with skeletal before we get into the other two examples. So skeletal muscle hypertrophy, generally speaking, isn't pathological. It's done in response to a stress. The stress is usually some form of muscular tension or resistance and the body freaks out and goes, oh no. But saying that, there could be situations where it is a pathological situation. You know, if you were to have

like a tumor with your pituitary gland and you're producing high amounts of growth hormone. But we'll get there. Yeah, that could be a pathological stressor. Yes. So excessive hormone stimulation or some kind of other signaling. Let's talk to that when we get to hormones as a trigger. But generally speaking, it's non-pathological. People want skeletal muscle hypertrophy. That's why they pay a lot of money to go to the gym, right? Yeah.

Right. So it's usually in response to tension. So exercise, we say, is great for everything. It's great because it is a stressor that the body responds to because it doesn't like the stress and says, I need to...

develop so that next time i'm exposed to that stress it's not as impactful impactful so you get bigger muscles as in response to lifting heavy weights right and that's skeletal muscle hypertrophy by definition skeletal muscle hypertrophy is an increase in the muscle size the muscle volume or the muscle cross-sectional area that's skeletal muscle hypertrophy

So if you were to say, based on that definition, you could have skeletal muscle hypertrophy, which is not actually coming from the contractile units. Yeah, that's true. So generally speaking, skeletal muscle hypertrophy can be broken down into...

And fibrillar hypertrophy, which is the contractile protein. And that's what most of us think of when we hear it. Yeah. You're creating more of those contractile proteins in the muscle that makes the muscle bigger. That makes sense. You get stronger, you get bigger. And stronger? Does it always mean stronger? Well, generally speaking, the more contractile subunits you have, the more capacity for contractile force to be generated, the more load can be lifted. So I would say that there's a direct association there. Now, I know you don't want to go into this, but I'm going to ask it anyway.

I've never been to a gym. I know. You probably don't know this, but I was, as you know, I worked overseas. If you say you're a world champion bodybuilder, there's no way I'm believing you. But came back from Australia. I was kind of halfway through a year before I could start uni again. And I just did like a six-month in, I don't know, exercise. It was either exercise or some kind of exercise.

No, it wasn't gym, but it's Certificate 3 in something like that, right? Now, there was something like that. I just did it for kind of not wasting time, but just filled in time. Something to do. Yeah, which was okay. However, there was like a mantra that, okay, if you want to build muscle, so just get bigger,

You kind of work within these sets reps. Oh, right. If you want to get stronger, it's less reps. Yeah. And if you want to get more tone, you're really working with high rep hypesets. Yeah. So with that, and I know you don't really want to get into it, but is there an idea that you can actually be stronger without a huge amount of hypertrophy opposed to...

which is not necessarily you're getting hugely stronger. Yeah. I mean, there is an association between the size of the muscle and the strength of the muscle. That's true. You can get hypertrophy and strength gains, and you can get strength gains and hypertrophy, but you can also focus on strength training and you'll get hypertrophy by definition. But if you're a bodybuilder, for example, you really focus on hypertrophy. Yeah.

And definition. And definition. Broadly speaking, what you said is sort of true, but what we know is that you can get skeletal... The evidence says that regardless of the resistance training regime that you undertake, you'll get skeletal muscle hypertrophy. And the rep ranges have been from anywhere between five reps to 30 reps of something. You can get skeletal muscle hypertrophy. Yeah.

Generally speaking, the lower rep ranges require a heavier load. Sure. Right? So you can recruit the type 2 fibres. To kind of get fatigued or just pre-fatigued. Yeah. So there's two major muscle fibre types, right? There's type 1, type 2. Type 1, slow twitch. These are the fatigue-resistant fibres. They're the first to get recruited. Yeah.

These are the fibers we recruit when we're just starting to lift a weight. Often they're stabilizers, less fatigable, all those types of things. Then you've got type 2 fibers. They're the fast twitch. They're glycolytic. They use glucose, no oxygen. They make ATP and use it quickly, but they also get fatigued a lot easier, but they generate a lot more force. That's the fast twitch. And so...

When you weight train type 2 fibers, the fast twitch, they have a greater capacity for hypertrophy.

And so the reasoning is that if you want skeletal muscle hypertrophy, then you might want to focus on the type two fibers more so because they've got the greater capacity, which is one of the reasons why people will lift heavier weights, do more explosive lifting, increase the volume. You get better skeletal muscle hypertrophy, increase the reps and so forth. At the end of the day, the point isn't how many sets, how many reps. The point is the volume over time.

So how much do you lift over time consistently? And so all the evidence states that it's not about sets and reps really, it's about consistency. If you consistently go into the gym and you are exposing yourself consistently,

to heavier and heavier weights and you're lifting it consistently over time, you'll get skeletal muscle hypertrophy. The body is made to adapt like that, right? You will have to. All right. Now I'm going to focus there. But this is not a podcast. No, of course not. We're not coaches or personal trainers. Sure. But I'm going to focus. Especially you. Actually, you're more qualified than I am to be. You've got a certificate in it. So focusing there.

So regardless of how the reps are set, whatever, when the body is exposed to resistance and stresses, how is it getting bigger? So what's the actual mechanism? Oh, yeah. Let's go back to what we're saying. Are there microfiber like tearing, which a lot of people refer to? Well, let's go back to what we were saying before. So we said that you can have –

Fibrillar hypertrophy, right? Which is increasing the number of contractile units, actinomycin. You can also get connective tissue hypertrophy, which is increasing the amount of connective tissue. So we spoke about the perimycem, epimycem, endomycem, but also the other connective tissue in and around those air compartments, right? So you can increase that. Connective tissue isn't static, it's dynamic. So it responds to stresses as well. So when you measure the cross-sectional area of the quadriceps, right?

Over time, it will get bigger and it's not just because you're increasing the amount of the fibrillar hypertrophy. It's also the connective tissue hypertrophy. But then you also have sarcoplasmic hypertrophy. Sarcoplasmic is also the intracellular components, the mitochondria, the glucose, the things...

the things inside the cells, you can increase that volume. And different training regimes can affect the type of hypertrophy you have. And that might be beneficial in more endurance-based, wouldn't it? Well, interestingly, bodybuilders tend to have more...

more relative to strength training, for example, sarcoplasmic hypertrophy. So more glycogen, more mitochondria, more of the intracellular products. It doesn't mean they don't have an increase in the fibrillar hypertrophy, but comparing some of the evidence has shown that, yes, that is the case. So they're the different types of hypertrophy that can happen at the muscle tissue. Yeah.

To be fair, if you want skeletal muscle hypertrophy, the connective tissue hypertrophy isn't skeletal muscle hypertrophy because connective tissue is outside of the cell. We're talking about increasing the cell volume. So that can really only be the fibrilla and the sarcoplasmic. Now you were saying the causes? Yeah, like what would be the mechanism for why or how the cell is getting bigger?

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Limited time, exclusively at a Sleep Number store near you. See store or sleepnumber.com for details. So there's three main proposed mechanisms. There's mechanical tension, there's cellular stress, and there's metabolic stress and cellular injury. They're the three main. Now of those three, mechanical tension is king. It is required.

Metabolic stress and cellular injury are neither necessary or required but their value adds. Right.

in skeletal muscle hypertrophy. And chances are they will happen concurrently. Well, that's the thing. The overlap between all those three things is significant. So you can have mechanical tension, but if it's not enough to stress the cell to a point where it's releasing certain metabolic byproducts, potentially lactate, ADP, hydrogen ions, it might not stimulate the cell enough to warrant significant growth.

Or the micro tears that might happen in the fibrillar tissue of the muscle, which is the injury, might not promote enough of inflammatory and cytokine response to stimulate cell growth, right? Yeah.

So, but they all work in and feed within each other. So you probably can't really get one without another to some degree. But at the end of the day, we know definite, we've known since the 1800s. I think there was a study in late 1800s that put dogs on treadmills and they identified that. So now he's talking about dogs. Yeah, good point. First time ever. That exposure to, um,

load over time resulted in skeletal muscle hypertrophy. We've known that since the late 1800s. Okay. Empirically. We've known that anecdotally for thousands of years.

So with the first one just briefly, which was the force load, so that would speak to... Mechanical tension. So that would speak to kind of a principle of mechanical transduction, which is you are putting a physical stressor on a cell and that cell is able to transduce a physical stimuli into an internal chemical one. That's right. And so that then...

transmitting that signal from the membrane being stretched to certain proteins on the membrane that stretches through the membrane can then activate a whole lot of internal chemical messenger systems. Absolutely. Which then instruct the nuclei to start to produce more contractile proteins. Yeah, so there's a couple of things that can happen. So exactly that, there is a pathway called mTOR.

which is a mammalian rapamycin complex. I wouldn't worry too much about it, but it allows for the transcription and translation of a number of genes. And these genes are... These genes turn into proteins and these proteins are contractile proteins. So mTOR seems to sit at the nexus of...

stimulating skeletal muscle fibers to hypertrophy by creating more protein subunits, right? That's mTOR. That can be stimulated via the mechanoreceptors that respond to resistance training. But there's also something called satellite cells, which are these quiescent stem cells. So quiescent is like you most of the time. A bit like liver as well.

Yeah, so they sit there, they've got the capacity to do something, but they need to be stimulated to do something. And so due to either mechanical tension or metabolic stress or if it's tissue damage resulting in inflammation and maybe cytokine release, all these things can tell the satellite cells to grow and

So they kind of migrate into the area of injury and they're kind of... That's right. And donate the nucleus. Differentiating to a muscle fiber. Sort of. They migrate to the area and donate its nucleus to that muscle cell. So the more nuclei a muscle cell has, like we said earlier, the greater the capacity... Do they die or they just hand off their nucleus and then move off? Good question. I think they just become incorporated in and basically...

And I'm just theorizing here, but it donates its nucleus and probably just gets resorbed back into the cell. I could be wrong. I don't know enough about it. But those quiescent satellite cells can get stimulated by all three of those stimuli. Okay. So that's the fibula, which comes about through tension and mechanotransduction. Yeah. What about...

So that's just workload within the muscle itself and it's just going through different phases of cellular respiration which then could be anaerobic or aerobic but the byproducts of that can then stimulate the muscle to grow. Yeah, basically right. So the chemical milieu of that local environment within the cell is

When you, for example, type 2 fibres don't require oxygen or often, well, it depends on the type 2 fibre. You can have type 2A and 2X. 2A can be oxidative glycolytic and 2X is mostly just glycolytic. Effectively, you can track those muscle cells enough. There's going to be metabolic by-products that are produced like lactate. And is this where, again, I'm not wanting you to...

Give the green light to this so a lot of people can't do it. But is this the theory of hypoxic training? So firstly, the things that are released, lactate, ADP, hydrogen ions, certain chemicals, other chemicals. They can, again, stimulate mTOR, but they can also stimulate a range of other effects to increase skeletal muscle hypertrophy. The basis of...

hypoxic training, meaning you put on a cuff, limit the amount of oxygen. Oh, the cuff. I thought it might have been like you wear a mask or something. Oh, no, no, no. You wear a cuff. You put a cuff around a muscle tissue. Let's say it might be upper arm or... Like a blood pressure cuff. Like a blood pressure cuff. You put it on. And there's protocols. There's protocols that are published online where you are limiting the amount of oxygen you can get into that muscle tissue. And it's harder for the blood to drain but also get in. So you get a...

in a way where you get this pump and that there's some evidence out there that says it increases skeletal muscle hypertrophy. But that's as far as I would go into it is that there's evidence out there that says that. I mean, I've spoken to some people who are better versed in this area who are experts, academics that I work with and they use the cuffs in certain types of training. They said the cuff, this is from their perspective, the cuff can be beneficial because

If somebody can't lift, let's say they've got arthritis, they can't lift a heavy load, right? But they need to gain muscle mass. They said that the cuff can be beneficial if used properly because you lift a lighter load and it fatigues the muscle earlier and increases the amount of metabolic byproducts that then stimulate the tissue. But there's dangers associated with this hypoxic training because one, you're limiting the amount of oxygen to that muscle.

How do you know how long to keep it on? How much to pump it up? Like there's expertise and training that's required here. I would not recommend anybody to just go in and cuff themselves and then go train. I think that could be a big problem. But yeah, metabolic byproducts, they can stimulate skeletal muscle hypertrophy as well. And one last question around this that I have for you is you also hear the different types of movement that you can associate with

with muscles for hypertrophy being, you know, a co-centric movement opposed to an eccentric or isometric. So this would be,

contracting the muscle whilst it's shortening, co-centric, contracting the muscle but it's staying the same length, isometric, or lengthening, eccentric. Is there any evidence that there's difference here in terms of how the muscle will get bigger? Yeah, there's some evidence that contracting the muscle through eccentric stimulates greater muscle injury.

to some degree, and that that might be a stimulus. There's some evidence also that the way that the protein subunits, the contractile proteins, are laid down can be different depending on if somebody does predominantly concentric versus eccentric. So an example there would be, let's just say if you did a bench press,

...that the eccentric movement is slowing the bar coming to your chest. So your pecs are lengthening but still contracting. That would be an eccentric movement. Then you're pushing it away from you. The pecs are getting shorter. That's a co-centric. So you're saying in that eccentric phase that...

The lengthening portion of it could be tearing the muscle? Yeah, yeah, potentially. Not off the bone but just the micro. Well, because it's trying to contract in response to a lengthening. So there might be an increase in the amount of damage that happens and that could be a stimulus and there is a little bit of evidence out there that says that

Eccentric training can result in the new contractile proteins being laid down in parallel to each other. Sorry, in series. So lengthening the muscle, right? And that concentric training, the contractile proteins can be laid down in parallel to each other, not in series, which thickens or widens the muscle, right? I read that in a single paper.

I don't know how much... This was a while ago that I read this. I'm just remembering this. Whether that's been recapitulated in other studies, I'm not sure. But that's... I do remember reading that. How true that is, I don't know how you would assess that. You just get somebody to do eccentric bicep curls for 12 weeks and then they investigate. I can't remember. But...

Yeah, so there's that. And then the final one was the stress, which we spoke about, the stress. And that can lead to inflammation and cytokines and they can stimulate mTOR and also the satellite cells. Right, okay. Anything else in terms of skeletal muscle hypertrophy? There is some conditions. So like an example is muscular dystrophy, which is a condition where I guess the dystrophin protein within the sarcomere

It's a genetically inherited condition and they lose the ability to, I guess, replenish that and then they slowly lose muscle fibres and the muscle fibres actually in some cases will start to uptake connected tissue. So in their case they have a form of pseudo-hypertrophy that particularly in their calves I think they look like they've got

Skeletal muscle hypertrophy, but it's muscles filling up with fat and connected tissue. Right. So instead of getting bigger through contractile proteins, it's filling connected tissue. But you'll be losing strength at the same time. Oh, that's interesting. I didn't know that. I think the other thing I'd just like to say is that relative skeletal muscle mass, so your relative skeletal muscle mass influences your glucose, amino acid and lipid homeostasis.

And because of that, the metabolic adaptations that occur in response to resistance training, so hypertrophy, is a disease modifier. Yeah, it makes sense. So going into the gym and getting bigger muscles can modify your risk of disease, such metabolic disease specifically, because your muscle is a strong sponge and regulator of the three major micronutrients. Makes sense.

Glucose amino acids and lipids. That's why it's recommended strongly for, say, type 2 diabetics. Yeah, because skeletal muscle, when under resistance training and exposed to exercise, can suck glucose in independent of insulin, which is great for type 2 diabetics. And can do so, I believe, throughout the day. So it's not only during the exercise, but it retains that ability throughout the day. So it becomes this...

this organ, this tissue that is able to kind of stabilize glucose levels. Yeah. So that then may assist with the requirement of medications to the same degree. Yeah, exactly. So that's skeletal muscle hypertrophy. Generally, it is a beneficial adaptation to stress. Let's have a look at cardiac and smooth very quickly. We'll start with smooth because there's more to them. Yeah. Can you just...

Well, tell me different locations in the body where you have smooth muscle and I'll tell you a couple of conditions that go with it. Gastrointestinal tract. Yeah, so gastrointestinal tract is just an 8-meter pipe, muscle pipe really, isn't it? Okay, speak for yourself.

So from mouth all the way to the anus is a gastrointestinal tract. So technically anything that could cause an obstruction could lead to the muscles responding to increase what's a demand, a workload. To overcome the obstruction. So upstream. There are some conditions like pleuric stenosis, which is congenital. It's still hypertrophic. And so this is usually...

Happens way more frequently in boys, infants. And for whatever reason, I'm not sure the mechanism behind it, but their pylorus, which is the distal end of their stomach, which is going into the duodenum, becomes hypertrophied. And that can actually be palpated in the abdomen. It's that kind of...

What's the word? Prominent. And the usual sign is once the baby starts feeding, the milk isn't able to pass through the polaris. When you're a forward thinker, the only thing you're afraid of is business as usual. Workday is the AI platform that transforms the way you manage your people and money today so you can transform tomorrow. Workday, moving business forever forward. They say opposites attract.

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Limited time, exclusively at a Sleep Number store near you. See store or sleepnumber.com for details. And they get regurgitation and then they progress into projectile vomiting. Oh, geez. So if it's going like after a feed, they're vomited across the room, that's usually a sign of polaric stenosis. Which is a type of hyper... Hypertrophy of the smooth muscle, yeah. Great. Which is fixed relatively quickly just by a surgical intervention. Renal system.

Oh, so the urinary, the bladder I'll use as an example there. I'm not sure if the ureter, I guess the ureter could, but that would... So the ureter is coming out of the bladder. The ureter is coming out of the kidney to the bladder. Okay, good clarification. Yeah.

But the bladder, the most common... So the bladder, its muscle being the truce muscle. Yeah. That muscle, its function is to empty the bladder. To truce. Oh, empty the bladder. Yeah. And one of the most... Well, in men, one of the most common aging unfortunate processes... Hair loss. Yes. Hair loss.

is prostate hyperplasia. So this is the prostate increases in number. But that results in the prostate getting larger. Wow.

That's not a hypertrophy? No, it's not. But what goes right through the prostate is the urethra. And so by increasing the size of the prostate, it impings the empty inability of the urethra. So it kind of backs up against the bladder and the bladder tries to overcome that pressure difference by increasing its size. So you're saying that the bladder...

in response to a hyperplasia of the prostate, undergoes hypertrophy of itself to increase the muscle size to overcome the pressure from the prostate because it's blocking the urethra. And the larger the bladder, the stronger the contraction, the more urine it can push out in response to the blockage. Arguably, yes. Oh, okay, cool. But...

I'm not sure how great a force it can do. Probably to the point where you can actually urinate, but it's probably something that needs to... So it's not like you're peeing 20 metres? No, no. Not like a, you know, as we did in the... I never did that. Never did that? No, I didn't have the... Like the trough at the primary school? I don't know. Where you have competitions with your friends? I... Trying to pee on the roof? I...

Pee on the roof. Just so you know, I never once had a peeing contest in primary school to try and pee on the roof. I think I was smart enough to realize that I would have peed on my head if I tried to do that or got somebody else's pee on my head. Well, you need to improve your aim, obviously. All right. So you're saying that most of the time, if not all of the time,

So smooth muscle hypertrophy in response to an issue is pathological? No, no. There's also physiological. So an example would be pregnancy, uterus in response to increased hormones. Oh, right. Because the thicker the uterus, so progesterone and estrogen, the stronger the contraction to push bub out of the canal. That's right.

Great point. Okay. Cool, cool, cool. There could be a situation like a leiomyoma. A what? Leiomyoma. Lei means smooth. Myomuscleoma. Oh. Growth. Yeah. So this would be essentially uterine fibroids. Oh, yeah. Fibroids, yeah. So this is just… Usually benign, right? Benign neoplasm. Technically, you would call it a…

You shouldn't call it cancer because cancer is by definition... It's a neoplasma. But it is a tumor. It's the most common tumor in females. And so it's a reproductive tumor that's generally a smooth muscle tumor within the uterus. But what they can do is because they become hungry for...

and progesterone, they can increase their receptors and that encourages more secretion. So they get bigger? They'll get bigger but they also suck the rest of the uterus to get bigger as well. Oh, the whole uterus can get bigger. Yeah, because that's, you know, they're androgens essentially, right? Yeah, the growth, growth. Okay. So... One other one which would be interesting is the respiratory tract. So you would see that in asthma because it's an obstructive...

Lung condition. CRPD maybe to a certain extent, but asthma, yes. There is both hyperplasia and hypertrophy of smooth muscle in the bronchioles. Right. And that is in response to a... Workload, probably workload, just breathing mechanics because you've got a narrowed airway, so you're trying to move air. More air out or in. But it would probably be also a, I don't know, a chemical...

messenger response as well yes like you know atherosclerosis is there's there's a degree of smooth muscle hyperplasia and that would come through more signaling i reckon than anything else all right so what about the heart what about cardiac hypertrophy because we know that that can happen in athletes but we know it can happen with people with certain chronic conditions so again there's physiological and then there's pathophysiological

So like you said, if the heart is a muscle, it is responding to a workload if you're an athlete and you're really stressing out your cardiovascular system and the heart is required to deliver more blood and oxygen around the body, the heart needs to be stronger in its capacity of pumping.

Now the muscle can be also instructed by probably the same mechanisms that you mentioned with the skeletal muscle, right? Stressor, so physical stress through the mechanotransduction but also through chemicals. It's probably a milieu of chemicals that would instruct the heart to grow in size but probably also the metabolic state as well, right? Yep. Now...

With physiological adaption, which should say through exercise, which maybe you can say is more of a healthy growth of the muscle, from my understanding, as the muscles are getting larger, so as the cardiac myocytes are getting larger, they are getting larger proportional, so width to length, which then makes the heart morphologically remains efficient.

Does that make sense? Yep. So it's still, it's growing in size. So you call this cardiomegaly because it's getting bigger, but it's still efficient. Yep. You know what I mean? Yep. That makes sense. I don't know how true this is, but they would say, you know, say Farlap's heart was larger than the other racehorses. Yes. So it would have a greater capacity to pump blood. Yes. Efficiently around its body. Yes. Without it being, you know.

...detrimental to its physiology. Yes. And you can have in certain pathological conditions... ...in response to, let's say, chronic hypertension...

or congestive heart disease, you can have dilated ventricles, which thins the walls, or hypertrophic, where it reduces the amount of blood that can get into those ventricles. So you can also get cardiac hypertrophy that aren't beneficial. So it's not making the heart more efficient, like you said, like in an athlete, but it can hit the point where...

The heart is responding to an existing pathology, which is overcoming a pressure. And often this can result in worsening the issue it's trying to overcome. But if this continues to go, it can put so much strain on the heart that it can result in heart failure. Yes. And look, I could be wrong here. Chances are I am. Yep, that's true. You are an idiot. Let's just say, just theoretically or hypothetically,

hypothetically, if you were to do an autopsy on an athlete and then a person with heart failure and you were just to open their chest and look at their heart size, both of them could have cardiac megaly which is just a large heart. Macroscopically, they might be indistinguishable where you might not be able to determine the difference between the two. But if you're then to investigate the heart failure one,

which is the heart is now not producing an output that is sustaining life or what the body needs and you were to look microscopically, so you would look at what each individual cardiac myocytes looks like, they are now morphologically not efficient. So they might be, what's the word, like thicker in...

opposed to length or vice versa, greater length or width. So it's not an efficient unit but it's enlarged. Yes. Does that make sense? Yeah, and I think that there is, I think we're not cardiologists.

But I would be confident that there would be significant overlap. However, you'd be able to tell to some degree the difference. It's probably got to do with the ejection fractions, how much the heart can pump out between the two. You know, they're both, I'm saying an athlete and somebody with a chronic condition, both with cardiomegaly or cardiac hypertrophy. They're probably...

got different ejection fractions, the amount of blood they're spitting out. They're probably going to have left ventricular cavity size differences, so how much blood can be filled in that cavity, how efficient that left ventricular muscle is at pumping the blood out. So there's going to be functional and anatomical differences. While you might say, yeah, there's cardiocarpotrophy in both, like you said, there will be some differences. But you'd need to speak to a cardiologist to be specific on those because I think they're still trying to

Look, I could be wrong, but let's speak to a cardiologist about this too. But you know that probably of physiological measurements, right? If you had an efficient athlete just by the way the principle of

...blood pressure and cardiac output works... ...if they've got a more efficient heart... ...their resting blood pressure... ...their resting heart rate's probably 40, right? Whereas if you had a person with heart failure... ...they're probably not going to have a resting heart rate like that... ...because they're...each stroke...

So the stroke volume isn't going to be producing the efficiency as you would see in an athlete. And there's likely a point in which an athlete's cardiac hypertrophy can become pathological. And we know that that can happen. So it can get too big or hits the point where it now becomes a pathology and is actually detrimental and not beneficial to the pumping of the heart.

And just how they can come about and those common ways that a person would develop pathological cardiac...

is usually sustained hypertension. So long-standing blood pressure issues. Another fairly common reason mechanism is valves aren't working effectively. So they're either stenotic or they're regurgitating, which is then just, again, changing the workload of the heart and making it grow in size to overcome that. There are some myopathies where you are...

the way that the muscle is being laid down and being instructed to grow become detrimental. But by far the most common causes of cardiac megalith or cardiac hypertrophy would be either through sustained hypertension or a valvular issue. Cool. All right. Anything else, Matty, on hypertrophy? No, I think we've covered the main things. I think so.

...without getting too bogged down in... Yeah, this could be big topics. But I think we did a good job covering hypertrophy broadly with the muscles. So great job me and you did alright.

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