Mar 19, 2025
"SPEAKER 0 All right, well, there's one person here other than me, so you guys all suck for that. Um, but OK, so we're going to talk about skeletal muscle. We've covered a ton of content since, um, before fall break and then fall break happened and then we're back right into it. Um, so I don't know if I can even cover all the content in this one review session that you guys have covered since, uh, starting before fall break, but I'm going to do my best to cover all the stuff. I'll probably move through some slides very quickly. I'm talking to you like you're my audience, so. Um, OK, so skeletal muscle, as we can remember back to the first, uh, week, I think of human, we remember that skeletal muscle is under voluntary control, meaning we control it, uh, with our central nervous system. It's again, our movement system. It allows us to sort of, uh, produce movement by contracting, pulling on bones, using that as a system of leverage that produces locomotion, so you can move. Um, it's striated in appearance, uh, and again, that is because of those contractile proteins that you guys now probably have a lot more background with actinomycin, um, that we will again talk about more in detail later and then they're also multinucleated, meaning they have a bunch of nuclei because they have to go under a lot of uh protein synthesis because um Again, they're very large cells like if you think about a skeletal muscle cell, it's the same thing as a skeletal muscle fiber, this very long fiber compared to like a normal cell, which would be like microscopic. So as a result, it has a lot of nuclei, and then again, like protein turnover is very high with skeletal muscle, it can be damaged pretty easily and then repaired, um. Again, pretty easily as a result of having those nuclei there. And then this is just nomenclature. muscle cells are special. They get their own sort of titles for a lot of these things that cells have. So just so you guys are, you know, can follow along in class, we start kind of using these terms interchangeably, muscle cell, same thing as a muscle fiber. sarcolemma is the same thing as your cell membrane. So we talk about the sarcolemma a lot when we're talking about when we generate that implate potential on that skeletal muscle where we're getting that handoff of the neurotransmitters that are then, uh, again forming that action potential on the sarcolemma. Same thing as the cell membrane. Uh, and then sarcoplasm, same thing as a cytoplasm. We remember that's just kind of the space within the cell, um, where all the organelles are sort of located. And then your sarcoplasmic reticulum. It is the same thing as your smooth ER from other cells. Uh, so the big thing you need to know about the sarcoplasmic reticulum is that it's going to be your primary site of calcium storage within the muscle cell. Uh, actions we talked about this a good bit, so a concentric action is where your muscle is shortening against the load, so you can think about maybe doing the up phase of a bicep curl where you're bringing your forearm closer to your bicep. Isometric is where you're still producing force, but the muscle is not changing any kind of length. So you can think about maybe holding a plank position or bringing like a curl up and just stopping in the middle of the range of motion. You're still producing force there. It's just the muscle length is not changing. And then eccentric. is where you are producing force, but um you're lowering or you're um the muscle length is increasing uh during that kind of contraction. So you can think about, uh, you know, you've done the curl, you're all the way up at the top, and then when you start lowering the weight, um, that would be your eccentric phase. So think about muscle lengthening, uh, yeah. And then in that case, your external force would be greater than your internal force, which is why you go down. Yeah. Components of muscle. So we think of muscles. They're almost like a Russian doll, and I'm going to pull up a picture after this just to kind of further explain this. But you know you have a muscle that's sort of your big organ tissue. There's the large contractile tissue and then within that muscle you have fascicles which are sort of like these tubes. That run within the skeletal muscle that hold the skeletal muscle fibers and then within those fibers you have the myofibrils, which are the contractile units, and then those myofibrils are then composed of sarcas. So I'm going to hit escape. I'm going to go over here and I'm going to find the picture that I'm thinking about somewhere hopefully. This is the first lecture. Oh, sweet. I don't see a picture of it. There it is. So as you can see, there's your muscle, uh, let me make this bigger. What? So this is your entire muscle. This is like your most outermost portion, and then you can see here this would be a fascicle kind of coming out like a tube. And then within the fascicle you have bundles of muscle fibers and then within those fibers, you have your myofibrils, and then within the myofibrils are your sarcas, which are those very basic like repeating units down the myofibril. Uh, we also have some connective tissue here. So you have your FIM, which is surrounding the outer edge of the muscle fiber. Then between fascicles here, you have your paramysium, and then between muscle fibers, you have your endomysium. So like I just think about a lot of times when we hear epi, we think about like it being a high order or the highest level of something. Um, like epigenetics would be an example of that. So it's your highest order, so it's going to be on the outside. Paramecium, maybe you guys have heard of like peri workout nutrition or peri, anything like that usually means like in between something or during. So, um, that's just how I remember. OK, your paramysium is kind of like the sandwich in the middle part and it's going to be surrounding your fascicle, and then your endomysium is going to be what's, uh, surrounding each individual muscle fiber. They're all just connective tissue. Uh, also something to note is that you, I think it's your paramysium. I want to double check this before I miss, but your paramysium, I think is what contains all of your neurovasculature that delivers that stuff, uh, to the individual skeletal muscle.
SPEAKER 1 Uh, let's see, vascul.
SPEAKER 0 Yeah, nerves and blood vessels. So that's where that stuff is going to be located. It's going to be within the connective tissue, the fascicle there. And then myofibrils, so this is going to be your actual contractile. Uh, proteins within the skeletal muscle you have actin and myosin. So, uh, myosin is going to be your thicker filament, and then actin is your thin filament. We'll get into a lot more of this soon, but some very basic things about myoin, you have two heavy chains, and this is going to be your myoin heads, and then your 4 light chains of myosin are going to be associated with the regulation of the ATPAC activity. Um, and then again, myosin, as we talked about with the cross bridge cycle, we know that we need ATP to um not cause that contraction, but cause the myosin to release from actin. So we have this myosin ATP hydrolysis reaction or myosin ATPase enzyme that's on that myosin that allows us. To once we have that ATP bind and associate, then we can go back down to ATP and inorganic phosphate, getting it back in that position. We'll go, I mean, that's like I just jumped ahead of time, we'll go into way more detail on that later, but that's just why it's here. Uh, and then thin filament actin. uh, so what you need to know about that is it is sort of your thinner filament, like I said, it's going to be anchored to your Z disc. We'll again get into all that later. Um, and it's going to have these regulatory proteins sort of attached to it. So it's going to have troponin attached to it and tropomycin, and those are the, well, troponin is your calcium sensitive protein that will kind of cause a series of events to occur after that that leads to myasin being able to bind. Again, I don't want to go into too much detail here because we're going to cover it in a lot more detail later, but I'm just wanting to give you guys like a 1000 ft view before we go further. Other regulatory proteins, so Titan, um, if you look at the sarcomere picture.
SPEAKER 1 I got to hit escape.
SPEAKER 0 You'll notice this like bead-like structure here. This is your Titan molecule. We don't really talk about it too much in this class. You might talk about it more in biomechanics, but know that when we're talking about the passive tension that we mentioned in class, a lot of that is coming from Titan. It's a visoelastic viso elastic protein within the um. Sarcair that is anchoring myosin to the Z line here and as you start descending or stretching something and this gets pulled apart, I'm sorry, it gets pulled toward the middle, this uh titan molecule begins to stretch out and sort of resist stretch. And something else to note about Titan is it's visoelastic and all that means is the faster that you stretch it, the, um, The higher the response it's gonna have. So if you stretch it really fast, it's gonna have a really robust response. If you stretch it slow, it's not gonna have as much of a response. So that's heightened. Yep, that's everything I just said. And then components of your sarcami. So you have your Z disc and again I'm going to go back to a picture in a minute, but just to explain it, your Z disc, that is just sort of your borders between each sarcomere. Remember those repeating units down a myofibril. So this is just like what is separating each sarcair, your actin filament, that's your thin filament like we just talked about. It does attach to the Z line and extends towards the middle of the sarcomere. Myocin is that thick protein that's sort of in the middle and it's going to be anchored to the Z line by Titan. And then your M line is just kind of your middle of the sarcomere, and that's where your mice and uh filaments are anchored as well. H zone. So these are, uh, I'll show you how I remember these. So you have 3 different zones. So you have your I band. This is where you're going to have only actin, OK? And remember I said actin is your thin filament. So actin is going to be associated with the I band. So that's going to be the area where there's only actin. There's not any myosin overlap, and I remember that because I is the thinnest letter. In the alphabet, like if you think about it, it's just like longitudinal like structure, right? Whoops. So it's a very thin letter, uh. Your H zone is going to be the area where you have your myasin filaments. H is a very thick letter. So that's just how I remember that. And then your A band is where you have actinomyasin overlap. And to me, when you look at the A, it looks like there's overlap like a cross here in the letter. So that's just my cheat code for remembering that very easily. I think it's useful. I mean, is it like physiologically sound and like super sciencey? No, but it's like a little cheat code that I have to remember that pretty easily. And then going into what this looks like. Again, here you have your Z1, like we talked about. This would be an adjacent sarcomere to the left and an adjacent sarcomere. Well, I guess that'd be the right, and then this would be to the left. H7. Myerson only we see that here. Right? Your M line is just the middle and that's going to be anchoring myasin. And then your I band is going to be out here. It's not shown for some reason, but that would be where you only have your actin. And then your A band is going to be this region here where we have actin and myosin overlap. Questions on that. I will draw this out. Oh, it's up here. I didn't see that. Yeah, I'll draw this out at the exam review. It might be a little bit easier to see that way, but just explaining how I take shortcuts, I think that can be useful. This is stuff we all talked about already FMICM, ParamycM, endomysium. Again, I think Epi as highest order period in between and then Eo would be the most like inside. I don't know, sounds similar to me, so that's just how I remember that. Some of this stuff is just memorization. I can't really like teach you this, but again remember pyroycM is going to be where you have that neurovasculature, so. Um, trying to think. I did not pull up the questions. Trying to remember where I got to before. I talk about motor units here? I do. OK. We'll keep you going for a minute before we pause to do the questions. OK, so motor units, when we're talking about a motor unit, we're going to be talking about a motor neuron, which we talked about that was like pretty much, you know, half of everything we we talked about in the last exam was neurons. So we're going to be talking about a motor neuron and then all of the muscle fibers that it innervates. Note that one motor neuron can innervate a bunch of different muscle fibers, OK. So when we're talking about fast switch motor units, these are going to be Uh, muscles that can produce a lot of force. In general, they're going to be a higher innervation ratio and all that means is that per motor neuron you have a large amount of muscle fibers that innervas. A low innervation ratio, I mean per motor neuron you have fewer fibers. Care if I ask you a question.
SPEAKER 1 OK, so you're, you're a good, you're a good crowd.
SPEAKER 0 Um, so, uh, do we remember when we use which kind or what the functions are of like a large innervation ratio compared to a small innervation ratio, like what's the advantage of them or when. Major muscle groups like gross movement, so higher innervation ratio, gross movement.
SPEAKER 1 Yeah.
SPEAKER 0 So finer movement, right? So, and I'll get into there is, we went over some of the reasons for that in class. I'm going to throw another one at you that really makes a lot more sense to me as to why that is. Um, and then we also have slow twitch motor units, again, smaller cell bodies, easier to depolarized. And just real quick, remember everything that we're, um, talking about when it comes to depolarization, we got to get to that negative 55. But remember that all those potentials that are hitting that cell body are graded potentials, meaning they're losing strength as they're traveling through the cell body. So as a result, these fast twitch motor units, they're harder to depolarize because their cell body is so much larger, larger. So as a result, there's greater potential to lose so much magnitude and strength that by the time they get to the like Axon hillock where that depolarization event could occur, they're a lot weaker. Whereas with slow twitch motor units, the cell body is much smaller, so they don't use, lose nearly enough strength. So to activate a fast-twitch motor unit, you have to have a very, very, very large, uh, stimulus, an excitatory stimulus for it to get it to fire. OK, and an all or none principle, this is just saying this is very similar to the same concept that we talked about with neurons where it's like, hey, you either generate an action potential or you don't, they don't vary in strength at all. Well, uh, muscle fibers kind of operate under the same kind of condition, whereas when that motor. I'm sorry, when that motor neuron depolarizes, every single muscle fiber that is innervated by that motor neuron is going to fire no matter what. It's not like, oh, it's not that strong of a stimulus, so maybe half the fibers are going to fire. It's like once it hits that trigger, all the fibers contract. Which brings me to the low innervation ratio. My way of thinking about that is because, well, we operate under all this all or none principle. So if you're able to have a lot more motor units in a given muscle that have smaller innervation ratios, and then they all operate under an all or nothing principle, then you get to selectively depolarize only a few in that region to have like a much finer movement. Does that make sense? So if you have like 500 different motor units in your hand, but you just want to move your pinky. Then maybe you can only be polarize 20 of them. Right, does that kind of make sense? You kind of pick up what I'm putting down maybe a little bit.
SPEAKER 1 Yeah.
SPEAKER 0 You get to have a lot more selectivity.
SPEAKER 1 I get that part, yeah.
SPEAKER 0 And then Henneman size principle, this is super, super duper important to understand. It will definitely be an exam question. It might even be a free response question, but this is talking about motor unit recruitment. So we just said. That motor units are described by the motor neuron and then the muscle fibers that it innervates. Know that when we are climbing up this um motor unit pool, we start with low threshold motor units. So this, and again, you're always going to be using low threshold motor units. I mean, this is stuff that we use for like posture, right? Your muscles always have some kind of resting tone, um, that are going to be controlled by low threshold motor units. And then Uh, like movements like walking, things like that, where we're not producing a lot of force, you're going to be using low threshold motor units. As we increase intensity, we um cumulatively increase motor unit recruitment. It's a cumulative deal. It's not like you just jump all the way up to these high threshold motor units and you don't recruit these anymore. You start from the bottom and you work your way up like stairs, OK? So, If you were to then like increase the intensity, then you're going to start recruiting some higher threshold murder units and remember that's tied back to the size of the cell body, and then once you depolarize those high threshold murder units, you're able to produce more force usually because the innervation ratio, so there's more fibers that are contracting. Once you get to like an all-out effort, this is incorrect. You will never in your life recruit all motor units unless maybe you're on bath salts or like, I don't know, you're a grandma that has to lift the car up, but we don't have access to all of our motor units ever under very, very Select circumstances where that happen. But just know that at this point we'd be recruiting in theory all of our motor units. So again, starting from low, working our way up to higher and higher levels cumulatively. OK, so it's not like you just jump from one to the other. Please don't miss that on the exam. And this is just applied. I kind of just went over this. It's just saying, OK, low intensity, you're jogging at a comfortable place at a comfortable pace, so you're going to be recruiting your type 1 fibers as the intensity increases and you start running faster, you're going to start recruiting both Type 1 and type 2 fibers and then at your highest intensity, let's say you're sprinting again, you're going to just be recruiting in more of those type 2, type, well, type 2 and type 1 fibers. Makes sense. That is where we'll stop for now. And then do you do the questions that I have you seen my questions? You want to try to answer these? And then we talk about this is how the reviews go. And then once you get through 123, just let me know when you want me to scroll down. There's like 7 questions. They are on Blackboard. How am I doing on time? Oh, we are so good. Just the 1st 7. You have no idea. Just say I have no idea, and then I'll explain
SPEAKER 1 it. Yeah. OK, I only answered no one. OK, which one?
SPEAKER 0 They're not numbered, so that's really cool, right? 123, 45. This one, right, so. Surround, which one surrounds, uh, each individual muscle fibers within the vasal? Do you remember that? your innermost one I see, right? OK, so A is off the table, skipping B because that's the right answer. Um, C, uh, organizes muscle fibers in the fascicles. That's just some made up thing. Um, stores calcium ions. Do you know what that is? I'll give you extra credit if you know what that is.
SPEAKER 1 Is that Yeah.
SPEAKER 0 So that only leaves one answer. Remember, epimysium is like your highest order and surrounds the entire muscle, so that external surface and it's producing, I mean, I didn't really mention this, but it does, uh, Add some like It makes it so like there's not a lot of friction. It can move smoothly. But yeah, FMICM is going to be your highest order, I guess, of connective tissue. Uh, are there any other questions about any of these? And then do you feel comfortable, or I'll I'll just tell you what the or do you want to tell me what your answers are?
SPEAKER 1 Yes.
SPEAKER 0 Alright, I'm rebuking your uh extra credit because I didn't realize that was a question that you just answered. But anyway, all right, uh, 3.
SPEAKER 1 This one is a guess, I guess B.
SPEAKER 0 All right, so Titan. Remember, that's that molecular spring that we talked about, that's on the inside of the muscle fiber. So, um Yeah, tropomycin, these are all. These two are your regulatory proteins that are sort of the ones that block bind the calcium and block the myasin heads. Myasin is just one of those, um, actual contractile proteins and then Titan, that's that elastic thing that's in the sarcame that, um, again, is resisting changes in length and it helps you again bounce back. And this gets into the past attention stuff that we talked about too. Uh, OK, this one. Um, I said, which for here. Yes, strepomycin, which one binds to calcium? Yeah, nice. What is the role that was the one we just did? OK. Thank you very much. Don't miss that. Um, right, and then this one. Yes, thank you. I'm so proud. All right, jumping back into content. This is your entire uh Muscle contraction cycle. I will definitely be pulling up slides to further explain this, but this is picking up exactly where we left off from again lecture two, where we had that um synapse occur at the end of the synaptic terminal from that neuron where we went through that saltator conduction process, had um the release of um acetylcholine, and then this is just picking up where that's leaving off. So again just to refresh, we have that action potential arrives in the axon terminal. That's that bulb at the end after self torque conduction that is then going to trigger these. All type calcium channels that are sensitive to voltage, that's going to cause calcium to come in. That calcium then binds acetylcholine, uh, containing vesicles, causing their release. Uh acetylcholine is then going to go into this, um, Space, what is it called? Synaptic cleft. I'm tired, guys. Um, synaptic cleft, and it's going to bind nicotinic receptors on the sarcolemma. That is then going to cause a depolarization event on the sarcolemma. And if you guys remember, sarcolemma is just the cell membrane of the skeletal muscle. And then once that happens, you get an influx of sodium ions just like we did when we were going through depolarization events on the neuron. And then that is going to cause a depolarization event at the level of the skeletal muscle, and that's going to generate an action potential on the sarcolemma that is going to travel down that sarcolemma, go into the T-tubule, which is just a like valley or gap in the skeletal muscle cell that's bringing it deep inside so that it can then make contact with other receptors that cause calcium release. Um, yep, and this is exactly where I left off. So T-tubule again, potential is going to come down. It's going to make contact with the DHP receptor, which are voltage sensitive. That DHP receptor is coupled with the rhyanidine receptor, and again I'm going to show a picture of this. I'm just, and we're going to talk through it again, but Um, it's coupled with a receptor which is sort of this plug in the sarcoplasmic reticulum. So remember we talked about like conformational changes, just means like a change in shape or something. So, uh, once that, um, DHP receptor is activated, it kind of unplugs the sarcoplasmic reticulum and that's what allows the calcium to exit and then from there it's going to make contact with the troponin and then you can kind of kick off your cross cycle. And now I'm going to try to find a picture of that. And I will go through it again. Muscle activation. Yes, so this is the first part of that. So again, remember ash potential is coming down, voltage gated calcium channels are activated. Calcium comes in. You then have the acetylcholine vesicle, which is releasing acetylcholine into the synaptic cleft. Acetylcholine is binding nicotinic receptors on the cell membrane of the skeletal muscle or the sarcolemma. You then have sodium in that's causing depolarization on the sarcolemma, generating an actual potential that isn't going to go down the sarcolemma. And Somewhere it should show a T-tubule. I don't like this picture at all, but this is essentially where we're picking up now, right? So we had that muscle, wow, muscle action potential generation coming down here. This is your T-tubule. I don't know why this is microscopic, but it is. You'll notice here you have the DHP receptor and your Randy receptor. You can see the conformational change. See how it's like a channel that was previously plugged by this, can you see that? Barely. I can barely see that and I'm standing right beside it. I don't know why this is so small. But yeah, again, actual potential DHP receptor unplugs this ryanodyne receptor and then from there you get calcium influx into the cytoplasm or sarcoplasm, excuse me, I'm not being correct. Um, and then from there, that's where your calcium is going to bind your troponin and then you kick off the crossroad cycle. OK, um. These images can be very overwhelming, but I pretty much just told you everything you need to know. I would recommend drawing this stuff out for yourself. I found that to be extremely helpful, and again, I pretty much just covered every single slide from here down in about 5 minutes. Um, Yeah. Cool. OK, and then Cross bridge cycle. This looks microscopic. Can you see that?
SPEAKER 1 Is that?
SPEAKER 0 No, OK, um, well, I'm just gonna read it. And it'll be posted, uh, I guess, yeah, I didn't really think this through that well.
SPEAKER 1 Um, so first thing that we're going to have happen,
SPEAKER 0 calcium is going to enter into that sarcoplasm. It's then going to make contact with troponin. OK. That troponin is coupled with tropomycin. They're kind of like a joint unit. OK. You can think of troponin is like the puppet master. It's running the show. It takes the signals and tells tropomycin what to do. And under resting conditions, or myosin, the myosin head is covered by tropomycin. OK. So once that calcium enters and binds the troponin, troponin tells tropomycin to pull off its like covering so that that myosin head is exposed. Um, that wasn't the thing skipping, that was my brain skipping when I stuttered, um. Yeah, OK. From there, remember this is a passive process. Myoin always wants to form a bond with actin all the time. It doesn't require ATP. Remember that's when we talked about the rigor mortis thing where like when you die, uh, and then you become stiff because you don't have any ATP that can unbind those actinomyoin sites. So, um, yeah, the myosin isn't going to make contact with that actin molecule. Also worth noting, when myosin is in its resting state, it's going to be bound by this ADP, which is adenosine, diphosphate, and inorganic phosphate. That's under its resting state and it gets that way through that myasin ATPase enzyme. So after myasin forms its cross bridge, it goes through this power stroke where it's going to pull, it's going to like pull this way, OK, so it's grab that actin, it's pulling it towards the M line towards the middle, causing the muscle to shorten, and it's going to use energy from that inorganic phosphate to pull the actin filaments again towards the midline. And the action is, of course, it's going to shorten the sarcamere. So if you think about muscle contraction, specifically a concentric contraction, your muscles get shorter. So again, that's a result of actinomycin pulling. Um, from there, ADP is going to be released. Uh, but the, um, Myoin is going to stay down. It's it's just in a low energy state, right? It's already pulled all the way out. It's like can't pull any further. From that point, an ATP molecule is going to come in, bind to myosin, and that's what is going to cause myocin to let go of that actin filament and then put it back in its high energy position. After that, you get reactivation of myosin through that uh myoin ATPase enzyme, again, getting us back to ADP and inorganic phosphate, and then that cycle is going to continue for as long as we have calcium inside of the sarcoplasm. So it's just going to keep going through that cycle. That is your cross bridge cycle. I'm going to find a picture of it and again go through that again hopefully. Uh, Hey man, Ian. I really don't like some of these pictures. This is way easier for me to draw, but I can't draw on these screens. OK, I'll use this picture even though I don't really like it. Um, OK, so again, where is Troponin. I guess this is assuming that troponin has already moved and tropomyocin has already moved out of the way, but we see this is your myosin head. It has bound an ADP and inorganic phosphate. OK. It then forms a bond. This is actin up here. This is sorry, myosin actin. OK. It then forms a cross bridge with actin. And then we see it's going to shoot off that inorganic phosphate, and you see how it's pulling the act in this way. OK, that's causing it to shorten. It's pulling it towards the M line. At that point, it's going to remain bound until we have an ATP molecule that's going to bind, it's going to release, which we can see here, and then after that again we're using this reaction, this myosin ATPase reaction to get back to ATP and inorganic phosphate. We're back in the high energy position. And that just keeps going on and on and on. Here's a picture of that rigor mortis where we don't have ATP, um, but that is essentially your cross bridge cycle. OK, from, from that level. Questions on that. That's a lot. But once you know it, like you should be able to explain it pretty quick. I mean, I know we spent a lot of time on this stuff and lecture, but literally I can run through all that stuff in like maybe 2 minutes. And if you can do that, then on the exam, you're going to be fine.
SPEAKER 1 I watch this like this right back.
SPEAKER 0 Yeah, I highly recommend, highly recommend. Um, these are just describing changes that we see in the sarcomere when we contract. So remember, we have our A band, that is our thin filament. Our H zone is where we have, uh, myosin only. Remember it's real thick. I band is actin only. A band is actin and myosin overlap. Z line is your border, and then this is just describing what's happening when that myosin is pulling on that actin with regards to the entire structure of the sarcomere. So because the actin is being pulled in. The A band is going to shrink. I'm sorry. That doesn't seem right. I'm sorry, the I band. I thought A for acting, and I just told you my mental shortcut. I'm so tired. Anyway, the I band is going to shrink because as the actin is being pulled into the middle, you have higher and higher degrees of actinomyoin overlap. Can you kind of picture that in your head where that thin filament was and now it's being smushed in. And now we have less um areas where there's only actin and more areas where there's um the H zone where you have the actin and I'm sorry, the A band where you have the act actin and myosin overlap. For whoever is watching this, I'm sorry if I'm really confusing you, but I'm going to go over it again. Um, H stone. is going to Hyoin. Yeah, it's going to narrow or completely disappear too. Again, that's going to be the areas of where you only have myosin. So your big trend that you're seeing here is that the areas where there is no overlap, right, your IBAN and H zone, they're going to get smaller. Why? Because myosin is pulling actin to try to pull it in towards the M line, creating a lot of areas where there's overlap. That simple. Uh, your Z discs, they're going to approximate because if we remember they're the borders of the sarcomere. So as your sarcomere is shortening, your borders get closer together. It's really that simple. And then I'm trying to see. Yep. This is exactly what I was saying. Um, your IBband is going to reduce and your H zone is going to reduce. Uh, a band should be relatively unchanged because that's where the overlap was anyway. Um, but, uh, yeah, do we see where this is your A band up here? The purple and now it's gone because acting, I'm sorry, Min has pulled it towards the center and then then uh this is your H zone and we see where that is also reduced because again there's um less overlap. It's pretty. Hard to notice here. Well, I guess you can compare these arrows, but that's what that's showing. OK. And then Muscle fiber types, or I'm sorry, calcium again, calcium saturation, this is just saying that once you hit a certain point of calcium that it has entered, you're not going to get any additional effect by increasing calcium because all of the troponin regions are saturated, therefore more calcium doesn't produce more of a result. And then you have a circa pump. Which its job is to once you stop sending that action potential, if there's a lot of calcium left over in the sarcoplasmic, I'm sorry, in the cytoplasm, it's going to try to pump that um calcium back into the sarcoplasmic reticulum so you can store it and reuse it. And that is an ATP dependent process. So that's an active process. Uh, and that's all that's saying and then fiber types. I'm gonna be honest. I'm not going to spend a ton of time on these because they're just memorization literally. What I will say for advice is just tie these back to metabolism. If you remember metabolism, that is like 70% of muscle fiber types. So if you remember that your type ones are more oxidative, meaning they're going to be using that beta oxidation or fatty sort of metabolism, then everything else, every other characteristic about them makes sense. Same thing with your glycolytic pathway. If you remember, um, Why, like the glycolytic is a faster process and all that stuff, then all that stuff is going to make a lot more sense. So what I mean by that. OK, if you just remember a contraction fee for type 1 is slow, force production is low, fatigue resistance is high. Why would that be? Well, it's because we're using oxidative metabolism which can produce a lot more ATP, so they're going to be a lot more resistance to fatigue. Also, if you guys remember back to glycolysis, namely anaerobic glycolysis. When we go through that cycle and we produce that lactate, we also get some hydrogen ions that can also cause fatigue. That's that like burning sensation that you feel, um. Again, mitochondria mitochondrial density, it's going to be high because again we're using oxidative metabolic pathways and all that oxidative stuff occurs in the mitochondria. Capillary density it's going to be high. Why? Because we need to deliver oxygen to the muscle because again it's type 1, it's oxidative, we have mitochondria, all that stuff. And then what's not listed here is we'll also have a high amount of myoglobin to be able to carry that oxygen from the hemoglobin in the blood. Get it into the uh. Skeletal muscle and then deliver it to the mitochondria. And then this is kind of your intermediate fiber. You're not really, you're, it's hard to ask questions about this because it's kind of moderate, right? Um. So I would just memorize these two and again if you know one, you know the other because it's just literally in the opposite direction. And then um if someone asks you like what kind of fiber is like moderate or is somewhat resistant fatigue or can do both aerobic and anaerobic stuff like pretty well, then you'll know that's type 2A just by process of elimination. I mean, yeah, it's important to conceptually understand that stuff, but Again, like for an entry-level physiology course, uh, again, just, just rationally think through this. Like, yeah, it's some memorization, but if you can tie again, every, everything's tied back to metabolism with this stuff. So if you can get there, you're like 70% of the way there. And this is just more talking about what I just said, mitochondria. Again, this is why you would have a lot of mitochondria and type uh type one fibers, because again, you're using oxidative metabolism and that requires oxygen and we do all that stuff in the mitochondria. So I'm not gonna repeat myself. This is just another way of looking at that, uh, based on aerobic metabolism, like I just said, um. I'll just click through these because again a lot of it is just what I said and I think I went a little bit overboard here. I will say um. Did you guys talk about lactate clearance ability or anaerobic stuff at all?
SPEAKER 1 Uh, there is OK, so remember when we're using anaerobic
SPEAKER 0 metabolism, um, we can produce lactate and, uh, your type 2 B through X, those are your highest, fastest witch fibers. Um, those are not great at dealing with lactate, but your type 2A are, and those are your intermediates. And then your type ones, you'll never really have a lot of lactate production from those because you're using aerobic, uh, metabolism, which does not produce lactate. Bicarbonate, you'll get a lot more into this. Know that bicarbonate is a buffer. Um, again, when you produce or go through anaerobic metabolism, you will produce hydrogen ions. That bicarbonate there is to neutralize that, um. I cannot believe it says this because uh Chad GPT has failed me. Lactic acid is not a thing. Um, cross that out. Don't listen to that. Um, and then phosphoreatine, we talked about creatine, that is your other metabolic pathway. It's your fastest by far your fastest metabolic reaction to produce ATP. It's good for about like maybe 1 to 10 seconds, it's like an all-out effort, um. That's your fossil creating PCR system. I know we talked about this a little bit in class. I don't think we went into a ton of detail other than, hey, this is that, there might be one question. I don't even know if that will happen. And then again, this is just more comparison if you want to look at it from an anaerobic standpoint, um. B ATP Yeah, I might have went a little bit overboard, but know that your fast switch muscle fibers are going to have a higher um My ATPA activity, that's what allows them to contract faster and harder because they're able to go through that cross bridge cycle at a much higher rate. Um, and again, force production, obviously your type 2 fibers are going to have a higher force production again tied back to not only the innervation ratio, just controlling more muscle fibers, but then also having a higher level of ATPA activity, and then you are going to have a lot higher resist, higher fatigue and fast fibers again because you're using. Uh, anaerobic metabolism to fuel that stuff. All right, that's where I wanted to get with that, and then we're going to go over these graphs. And I got more questions for you. Oh, that was a lot.
SPEAKER 1 You feel like I just like threw up on you
SPEAKER 0 with like all this information?
SPEAKER 1 Yeah.
SPEAKER 0 Uh, do you see where like the lines are? That's your section, yep.
SPEAKER 1 They flew through those. Alright. Oh sweet, OK, um, so what we get for I
SPEAKER 0 guess 8 or 1 of this section. Yep, nailed it. OK, 2. Good.
SPEAKER 1 3.
SPEAKER 0 So remember, we have to generate some energy from somewhere to get my in the pool, right? And then, uh, again, if we think about resting conditions, myosin is going to be bound by what? You can say I have no idea because I'm probably not asking this in a very good way. So under resting conditions can have ADP and inorganic phosphate. OK, that this is inorganic phosphate PI anytime you see that, that's what that means. Yeah, so it shoots that inorganic phosphate off. Remember, that's the way we produce energy, a lot of times breaking phosphate bonds, so. That's what's allowing Myerson to pull Acton. Uh This one? Yep. This one Yeah, good job. And then 2 more. No. D is correct. Remember, so that's the whole point. Once you have saturated, and this goes back to early physiology, once you saturated all the receptors, if you increase, and this isn't really a ligand, but just as a general example, it doesn't matter how much supply you have, it's a demand-led process. Does that make sense? So like if you have all your receptors are occupied, it doesn't matter how many more things that you're sending to them, they can't do anything else. So if we have calcium saturation. Then all the troponin molecules are going to be, uh, bound to calcium. So then you wouldn't be able to form any more cross bridges. Yes, what else would shorten?
SPEAKER 1 What else should we besides?
SPEAKER 0 Yep, 2 things. Yep, HM.
SPEAKER 1 A event.
SPEAKER 0 Your A band is going to stay the same. Because that's where the the overlap is short and the zone, yeah, yep, got it. And then, oh dang, I have all these questions on fiber types.
SPEAKER 1 Oh, I was supposed to, that's why it felt like
SPEAKER 0 I was going forever. I didn't realize I'd broken it up. OK, why don't you go ahead and do.
SPEAKER 1 Let me, let me, let me finish lecturing on this
SPEAKER 0 stuff and then we'll do the remainder. But I covered that on accent, OK. We have gone over and I'm happy about this because this was when I took human physiology, we did not talk about this that much, but I think this is incredibly important to um skeletal muscle physiology and something that we definitely, you guys should know about. So, This is your length tension relationship of a sarcomere. There is another one that we're going to look at next that is going to be at the full muscle, and that means we're looking at both physiologic strength, meaning sarcair, and then also passive tension. OK. So this is your sarcomere only. So, What we see here, uh, this area from this A area, if you guys want to like, I guess if you're watching your exercise or whatever, but if you pull your forearm all the way up, so like you're making a bicep, that is where we're starting at the very bottom of this graph down here at the 60. Whoops. Region. And then if you start like letting your arm kind of fall down to the side like you're doing an eccentric bicep curl, we're crawling up here. OK. So what this is showing is that when your muscle is at a very short position, like when you have a very flexed arm, you have a lot of Overlap between actinomyoin. So when there already is a lot of overlap, uh, you can't form as many uh actinomyoin cross bridges because myosin isn't able, like if you think, if you see here this is your A band, I'm sorry, your, um, actin filament up here. Myoin can only form cross bridges going this way. Does that make sense? It can't reach back and grab the ones behind it and then continue to pull them back. Is that, is that, are you following what I'm saying? OK, so you want an ideal length, which would be up here. Where myocin can then uh reach out and grab Ain and form a lot of different cross bridges as a result of the position of actin relative to myosin. Here it's too short. There's too many behind myosin where it can't grab it from here to here. This is like ideal scenario, OK, this green zone, that's where you have uh maximal uh opportunities for myosin and actin to interact because the actin is in a very favorable position. Um, this is also called your plateau. This is, you don't need to know this. I'm not even going to throw that in there to confuse you guys, but um, yeah. As you start Like if you're in this, I don't know if we talked about this, but this happens to be a resting length for most muscles. So like whatever the resting length is, like if you're just having like a normal posture, that's generally where it's going to produce the most force. If you begin stretching a muscle, you can see that these actin filaments get pulled further and further apart. Now it's like the the myasin can't reach far enough forward to grab onto those actin uh filaments and then pull them back. So as a result, we have a decrease in the amount of force that we can produce at those joint angles, which is again dictating. The overlap here of actin and myosin because myoin cannot reach actin and this would be like the worst case scenario like maybe you can form one cross bridge here, maybe that one can reach here you have less that can reach and then again opposing that over here where there's so many behind the myoin that it can't reach behind it, we can see that these areas here are both weak positions. Up here where we have optimal overlap, I'm sorry, optimal, I guess length between them, that's where you're going to be the strongest. This is probably everything I just said. Um, Yep, too short, sarcommeres are too short. You have actin filaments that interfere with each other. Fewer cross cross bridges can be formed, and then you have reduced tension, and the same thing occurs when it's too long. Fewer cross bridges again because myasin now can't reach, and then again you also have reduced tension for the same reason. It's just a different sort of mechanism. You're not able to form enough cross bridges. OK. This is the exact same curve we just looked at. It looks the exact same. So this is your physiological strength or your strength that's occurring at the sarcomere. And then what we have here, this darker line here and it says passive here. I just want to point that out. I actually like look at, I'm bad at this. I'll just look at something I'm like I don't even know what I'm looking at and not orient myself to the picture, but this is your passive tension. Passive tension is going to be mainly coming from Titan, which is that visyelastic protein that we talked about earlier that's in the sarcomere that it's going to respond. It's going to resist stretch. Uh, and then also including in your past attention are going to be like your FMIM, paramycM, endomysium. Those are made of collagen, um, so they're also sort of a passive, um. Tension generator, um, soft tissue in the body. So as you'll notice that as we start stretching a muscle out, we're losing, uh, physiological strength because we can't form the actinomyoin cross bridges, but it gets to a point when we start stretching out and stretching and stretching and stretching that that titan becomes pulled so strong that it is generating a lot of tension in the muscle. So then we get an increase in passive tension. And anytime you think about like, hey, maybe how can I think about this? Have you ever stretch your hamstring and the further and further you go back, it starts getting really, really tight and then at the very end range of motion, like you'd have to really, really push it. To, um, be able to push it back any further. Um, again, you can see how rapidly past attention increases, uh, with increased stretch, right? Um, and then this up here is going to be your total force between both active and passive tension. So again, physiologically weaker, but then we start compensating in a stretch position rapidly with um titan and passive tension. Whoops. And then as a result, our total tension goes up. So the total tension that can be produced by a muscle is actually stronger in a stretched position because you have so much passive tension there. Makes sense. Again, this is what I said too short. You have too much actinomycin overlap, and then you're also not even tapping into any kind of past attention because there's no stretch going on at the muscle. Too long, you will start to have a decrease in actinomyoin overlap. However, you will start getting increases in past attention which is going to contribute to the total amount of force that muscle can produce. Um, And then this is just describing passive tension, which I just did, and then noting that total force is going to be the sum of both active and passive tension and the total force of the muscle is gonna usually occur in a stretch position. Uh, this is just talking about Titan again. It's like a spring, and the more that you stretch it, the more tense it gets. And again, it's visoelastic, meaning the faster that you stretch it, the more force it's going to produce. And just a fun fact, you cannot stretch every single muscle in your body in the true sense of the word, meaning that you're getting into passive tension. That is going to be dictated a lot by joint structure, so it's very hard to stretch your bicep. Because your elbow, like that's just how the joint is. And what we mean by stretching is that we're actually getting into passive tension. And this, again, I don't want to waste too much time on this. If you guys want to come nerd about nerd out with me about this during office hours, I'll be happy to do it, but we're running on time. And then I want to make sure I get to the force velocity curve because this really tripped a ton of you guys up in class, you guys. Um, yeah, and I get it, right? So, um, Orienting and I like this one because it's literally telling you, hey, this is concentric, and then this is eccentric. Concentric means we're performing a shortening muscle action, eccentric meaning we're performing a lengthening muscle action, and then isometric is right here in the middle. Velocity is a vector unit, meaning it has magnitude and direction. I could easily put a plus side on this side, and that would be a positive direction and a negative side on this one, and that's a negative direction. Positives and negatives in physics don't necessarily mean positive and negative values like numerically. They're more related to directions. So I don't know if you've had physics or like familiar with any of that, but a lot of times in physics you'll be like, oh this is occurring in the positive direction or the negative direction. It doesn't necessarily mean the value is negative. So anyway, um, what we see over here, uh, force is on your y axis and then velocity is on your x-axis. OK, so velocity is both increasing this way and this way because they're directional. Again, remember, concentric is shortening, so you're going up, eccentric is lengthening or going down. Another way to think about it is concentric is your positive direction. It might blowing your mind. You're just like nodding. If you, if you, if you, yeah, concentric will be your positive direction, eccentric will be your negative direction. Velocity can both increase in the positive and negative direction. I don't want to over like blow your mind too much with this, but all this is saying is that when velocity is very high, because remember it's increasing this way, it's increasing to your right, and force is low over here. So if you have a high velocity contraction. You are going to have a low amount of muscle force. Also, before I forget, and I always do this because I, I just know what it means, and I even wrote it and read and I forgot to mention it, but when we're talking about force here, force and physics we describe as force equals mass acceleration. This is not what that's talking about. This is talking about the force at the fiber level, which is again directly proportional to the amount of actinomyoin cross bridges that you're forming. Now, the reason that's important is because actin and myosin, they take time to form cross bridges, which is why when you have a slower velocity of contraction, you have a higher force because you're able to form more actin and myosin cross bridges directly tied back to that APAS activity. Where you're able to, I feel like I'm really. Um, well, it's important to know this, this is like testable stuff. Um, so again, if you are able to have a longer duration of time and can go under more of those mice and ATPA reactions and form more cross bridges, you can have a higher amount of force.
SPEAKER 1 So like The lengthening side over here, yeah, yeah, that would be like more force, right?
SPEAKER 0 Yes, because again, remember that's your y axis, so yes, you can produce more force eccentrically than concentrically.
SPEAKER 1 Yeah.
SPEAKER 0 Um, so over here again, a very fast concentric contraction is going to have a low low amount of force at the fiber, not like outside. The slower you go, the more cross bridges you can form. And then as a result you end up producing more force. Isometric is where you're sort of perfectly in the middle between eccentric and concentric where you don't have any movement occurring and then as velocity increases eccentrically you can produce a lot more force. This we didn't really talk about too much. It is a bit more complicated, um, but something to know is that You're having to form less cross bridges eccentrically because the muscle is lengthening. So the myocin is not having to pull actin towards the midline. It's having to form less cross, it's just kind of guiding it back. And then the other thing is again we talked about passive tension. Once you start getting into a stretch again, remember that's associated with eccentric muscle actions, and when you get into a big eccentric, then your force production goes up and then yeah, the faster you go, technically if you were to stand on like a ground reaction plate, you would see a lot more force eccentrically. That's a lot. Um, this is everything I just said. I'm gonna just leave this here. If anyone's watching it and wants to pause it and read it, cool, but that's as far as I got. We are right at 7:03 and you have maybe 5 questions to answer now, um, if you want to. Or you can just be like, it's 703 and I'm going home. The answers are, there is a key. OK, yeah, fair enough. All right, so that's that. stop recording. " "SPEAKER 0 All right, what's up guys? Um, so first and foremost, sorry for the delay, um, although I don't think any of you are actually in either of the rooms here, so probably not actually holding anyone up, but we are getting started, I don't know, maybe 15 minutes late. Um, essentially, I couldn't get my mic to work, um, so I had to restart everything. I tried opening a bunch of different browsers and all that, and none of that worked. Um, so yeah, that kind of sucked. So anyway, plan for today, I am going to go back and we're going to review muscle fiber types a little bit more because I didn't feel like I was able to spend enough time in my initial review session on that content, um, and then we are going to get into some propria up your stuff. After that, we're gonna kind of look at the mechanisms of muscle fatigue, um. And then smooth versus cardiac contraction and then we are going to review some of the content that we did from exam one regarding absorption and transport within sort of the GI tract, how we're getting nutrients across the cell and kind of what's going on at each one of those places and then from there the next session we'll go into is going to be all that new content, um, for the exam. Know that all that stuff from exam one is going to be fair game, but um you should definitely spend your time mostly on the new add-ons to what we already covered and that um. Exam one stuff. So sort of like the post-absorptive stuff that we talked about, uh, the hormones that kind of influence gastric emptying, stuff like that. Um, but that will be for next week's review. Um, yeah, also in terms of questions, um, I currently don't have any questions. I haven't had time to make any. We had midterms last week and the week before, and, um, yeah, I've just been super busy. That's kind of why we've had to rearrange some of these um review sessions, um, but after this week, we should be back on track and uh yeah, we'll be closing out the semester pretty soon. I can't believe how fast this has gone. All right, so. Getting in here. We can start our review. So, there are several ways that you can kind of classify um muscle fiber types. Um, let me just make sure that I'm actually starting on the right slide that I wanna. Start with, yeah. Um, so I like to, you can either group these by their mechanical sort of characteristics like contraction velocity and stuff like that, or I like to personally group them mostly tying them back to metabolism. So you'll notice that we have our Two main types, technically there's 3, but we have our slow twitch, which is type 1, which we have of course here it's a shortening or a lower shortening velocity and slower contractions and then our type 2 which are our higher shortening velocities and rapid contractions um and then we also are, uh, I mean technically the type 2 or type 2A and then type 2 B through X, we can get into that a little bit more, but um. Underneath here I have whoops. Sort of our major metabolic pathways um that we talked about earlier in the semester. So you have your glycolytic pathway and your aerobic pathway and uh a new one which is your ATP PCR system. This is your. Don't really talk about um too much early on, if at all, um, but it's really not nearly as comp uh complicated as like glycolysis or beta oxidation. Um, so yeah, this is a, a way of grouping the stuff. I'll show you what I mean. So, uh, sorry for the very, uh, small font here, but I wanted to kind of have this as like a master slide, um, so you can kind of compare and contrast everything. Uh, this is more based on The metabolic sort of functions of these muscles. So as I mentioned, your type one are going to be your slow twitch, your oxidative fibers, and if we remember when we're using oxidative metabolism, it is going to take much longer and it's going to require oxygen and the use of the mitochondria. So if we can think about that, if we remember that. Our oxidative pathway is producing much more ATP. We know that we are going to be a little bit more resistant to fatigue because we're going to have a higher level of energy available to us as well as if we recall back to when we're doing anaerobic glycolysis for energy that we're producing some hydrogen ions and lactate and those as we'll learn coming up can cause skeletal muscle fatigue. Of the skeletal muscle. Um, so those are your two reasons, uh, that you're gonna have higher fatigue resistance. So think higher ATP payout and you're not going to be dealing with a lot of acidity due to this hydrogen ions. Uh, primary energy source, again, aerobic oxidative, uh, and then uh type one, you're going to have to have a lot of mitochondria because if we go back to um Metabolism, we know that oxidative phosphorylation, that process of metabolism is going to occur in the mitochondria. So as a result, you need a lot of mitochondria to be able to support sort of energy yield there. Capillary density again high and again if you just tie it back to metabolism and think from a functional standpoint, if you are going to need to deliver oxygen to the muscle while we do that through blood, right? So it makes sense that we would want a higher level of capillaries in the muscle to be able to deliver that oxygen to the mitochondria. Therefore, again, being able to produce a lot more ATP. And in terms of activities, you know, your type one fibers really, it's anything from just like sitting around, uh, you know, sort of postural muscles, things like that to like walking around or even marathon running and stuff like that. Uh, that's all going to be your type 1 fiber activity. Uh, moving from there, we get into type 2A. These are your hybrid muscles. Um, so these are kind of like a jack of all trade master of none. They can do a little bit of both. Um, some people argue that they're the best fiber types. I, I don't think it. Matters, but um uh essentially what you're gonna have here is the contraction speed is gonna be fast. um you're gonna have a moderate resistance to fatigue because you're gonna have both aerobic and anaerobic pathways kind of occurring here. You are gonna have some mitochondria here, although not nearly as many as type one fibers, um, capillary density again not gonna be as dense as your type one fibers because again you have less mitochondria. And uh yeah, so it's just kind of this in between uh fiber type you're probably not gonna have as many questions on that just because it's in my opinion harder to write exam questions about something that's kind of in the middle and then moving from there we get into our type two, and again this is B through X and just know that this is not saying they're B and X, there's literally isoforms of Muscle fibers ranging all the way from B to X, and the closer you get to an X uh type fiber, uh, the more oxidative it is. So the more that this characteristic is kind of true. So this is going to be your highest contraction velocity, highest amount of force production, very low resistance to fatigue, so they're going to fatigue very quickly but because again we're going to be using anaerobic glycolysis for the most part, and if we remember that's going to produce very little ATP compared to something like oxidative phosphorylation. And then also we'll see that we are going to be accumulating some hydrogen ions and we'll talk more about those deleterious effects coming up. And then in terms of mitochondrial density low again we're not using oxidative pathways here so you don't need a lot of mitochondria and then in terms of the capillary density again low, you don't have a lot of mitochondria, therefore you don't have to deliver a lot of oxygen to the mitochondria. And in terms of activities you're looking at things like Jumping, short explosive movements, so sprinting, uh, weightlifting, and when I say weightlifting, I mean the actual sport of weightlifting. So like, you know, clean and jerk, snatch, that kind of stuff, your explosive movements, um. And like, you know, really, really heavy, uh, weight lifting, uh, I guess more generalized to just like the gym stuff, yeah. So this is kind of what I talked about earlier if you want to organize it again based on metabolic capacity again, if we recall back mitochondria, again, we have to have that to produce our ATP through oxidative phosphorylation. That's sort of your last step, um, once you get through glycolysis and then you go into the crap cycle, everything after glycolysis is going to take place in the mitochondria, myoglobin. This is just skeletal muscle's version of hemoglobin, and again that's sort of our Oxygen delivery mechanism to the muscle. So, uh, myoglobin is just like literally saying, hey, this is how we're carrying oxygen within the muscle. Capillary density, again, we've covered this a lot, but again, we're having to deliver the oxygen to the muscle and then connection to oxygen, uh, again, this is just everything that I've just said, right? It works together to ensure oxygen is stored, transported and utilized efficiently for prolonged activities. Uh. Again, this is just organizing everything sort of based on their aerobic capacity. You'll notice that type 1 is the most well suited for this because you're going to have high mitochondrial density, high myoglobin, high capillary distance or density, and then high fatigue resistance, um, and then sort of you're going to go down. Uh, I guess, levels of aerobic capacity, uh, with your type 2 B through X being the lowest. So if you just remember that type 1 is going to have, uh, sort of a structure that is very well suited for aerobic capacity. Uh, you'll just know that type 2B through X is going to have the opposite of that. So it's gonna be very low. And then anaerobic capacity again we have the ATP PCR system. This is sort of how creatine works. Essentially you take some creatine and then you're able to uh phosphorylate that creatine and store it as creatine phosphate or I'm sorry, phosphoreatine, and then during a very intense act like activity you're able to liberate some of those phosphates off that phosphoc creatine and then essentially.
SPEAKER 1 You'll be able to resynthesize ADP to ATP very quickly
SPEAKER 0 because you just have a little bit more extra phosphate stored there. Uh, from an anaerobic glycolysis standpoint, again, we talked about this a lot earlier on. This is just kind of talking about, um, you know, the process where we're breaking down glucose and then remember we can either go one of two ways. If we're anaerobic, we're going to produce lactate and hydrogen ions which can then lead to fatigue um if we're, uh, I'm sorry, if we're anaerobic, and then if we're aerobic, we're gonna go and take that pyruvate and then transform it into acetylchoA and then enter into the grav cycle and then lactate again, this is a byproduct of anaerobic glycolysis. Uh, note that lactic acid is not a thing.
SPEAKER 1 What you end up having is you have lactate formation and then hydrogen ion accumulation and then It just so
SPEAKER 0 happens that those things are imported or co-transported out of the cell through this thing called the MCT transporter, uh, outside the scope of this class, but just know that lactic acid, um, is kind of a misnomer.
SPEAKER 1 Uh, that's not really how it.
SPEAKER 0 Uh, exists, and as soon as it exits the cell, it dissociates and it just lactate and hydrogen ions. Uh, and then also note that that lactate can then enter into the co cycle again outside the scope of this um. Class, but a lot of people talk about lactate in a negative light, uh, you know, they'll talk about lactic acid and all that stuff again, untrue and lactate can actually be of benefit for us, uh. We can actually convert it to glucose in the liver.
SPEAKER 1 And I'm gonna probably be coughing a lot. I, uh, have some, I don't know, allergies or something
SPEAKER 0 going on. So sorry if I'm like coughing in your ear. But anyway, so. Again, when we go into more anaerobic things, we're going to be talking about also bicarbonate because again, if we are producing a lot of hydrogen ions, we're going to have something there that is going to help us neutralize that acidity, and we talk about bicarbonate with that. So your type 2 fibers, namely your type 2 A fibers are gonna have a very high supply of bicarbonate that is going to help them tolerate that hydrogen accumulation better, um. Let's see. This is just talking more about phosphoc creatine. Sort of it's um Role in producing energy in a very short amount of time and then from a glycogen storage standpoint we're going to be looking more at type 2A and type 2B X um fibers because again we remember glycogen is just stored glucose and if we're going to be using mostly the uh glycolysis to produce energy, we're gonna need glucose, so that makes sense. And again Uh, for here anaerobic characteristics, your most, uh, your best suited, uh, fibers for anaerobic stuff is actually gonna be your type 2A, um, because they can use that anaerobic, uh, sort of system, but they're just better at tolerating it. They have a higher amount of like fatigue resistant qualities. So if you'll note here like their lactate clearance ability is much higher. Their bicarbonate uh supply is um Fairly good. Um, so, yeah. And then if we're moving down here, we'll note that the lactate clearanceability of like type 2, B and X fibers is a little bit lower and then um Yeah, so just kind of logically make these connections in your head. You don't have to memorize everything as long as you can just get the trends down. Uh, these are just ways of kind of organizing the fibers, uh, and just again really pointing out that these are all tied back to metabolism. Uh, and then we can talk about the mechanical properties. So this is all going to be tied back to like your myasin ATPAC activity, uh, force production, and, uh, like fatigue kind of stuff. So remember, min HTPA is an enzyme that allows us to um. Sort of take that ATP molecule, transform it into an ATP and inorganic phosphate, and then be able to continue the cross bridge cycle. So if you have a higher amount of that ATPA enzyme, you're able to form cross bridges at a faster rate. So yeah. And then that is directly tied into force reduction. When you can perform more cross bridges quicker, you can pull on that actin molecule harder and faster and then ultimately produce more force. Um, yeah. Again, this should all make sense based on that. Uh, type one is going to have a very low myosin ATPA concentration. Therefore, the contraction speed is going to be slow, production is low, um, and the, uh, again, endurance fatigue resistance is going to be high because you have less ATP turnover because again, if you remember ATP doesn't cause contraction, it causes the release of myocin. From Acton, but again, uh, ATP is still utilized to be able to again return mice into that high energy position so that you can form more cross bridges. Type 2A, moderate pretty much across the board. Nothing really stands out there, and then your type 2B through X, highest contraction speed because again you have the highest amount of mice and ATPA activity, so you're able to go through.
SPEAKER 1 Cross bridges at a much faster rate, um, and produce
SPEAKER 0 more force. Uh, this is the uh link tension relationship. I feel like I did a pretty good job covering that in the last exam, and this is something that we'll definitely cover in the exam review. If you have any questions about that, just let me know. Blah blah blah. Uh, again, that is your total length tension relationship and then This is your force velocity curve. Again, I felt like I covered this pretty well in the exam review kind of at the expense of uh
SPEAKER 1 fiber types because again, in this class compared to the
SPEAKER 0 physiology class that I took, we did not spend a lot of time. On, uh, any of these graphs, but I think that they are very important, um, to really understand what's going
SPEAKER 1 on at the uh fibers both from like a tension
SPEAKER 0 standpoint and a force velocity standpoint. So This is our new content, um, that we are gonna be covering. Uh, since, I guess, I don't know, we came back
SPEAKER 1 from fall break maybe or I, I, I can't even remember my days are so jacked up in weeks. So anyway, I'm just going to jump into content.
SPEAKER 0 So, These are gonna be your mechanisms of skeletal muscle
SPEAKER 1 fatigue. Um, there are two ways that we can actually generate fatigue, um, for your skeletal muscles. One is gonna be peripheral. Uh, peripheral just means anything kind of occurring outside of the central nervous system, so it's really occurring at the level of the skeletal muscle. Um, so the three that we have here is we have conduction failure. So we talked about this in class, so we have a buildup of potassium and the T-tubule, and what happens is, um, once you're sending a bunch of action potentials
SPEAKER 0 and you're going through that repolarization event where you have
SPEAKER 1 a bunch of potassium leaving the cell. Um, sometimes it can accumulate in that, uh, T-tubule, right? And if we remember anything about concentration gradients, things wanna go from a high concentration to a low concentration. So if you have a bunch of cows or potassium that's built up in that T-tubule, then what ends up happening is you're not able to go through that repolarization event because potassium is not able to leave.
SPEAKER 0 And then we end up having a situation where we're
SPEAKER 1 just constantly staying in a depolarized state, which obviously that's kind of synonymous to like an absolute refractory period. So if we remember the sodium gets have to close, we have to then return down to our resting membrane potential which is again the function of potassium leaving. And if potassium is unable to leave, then we're never able to get back to a situation to where we can then generate another action potential. Um, so that would be conduction failure.
SPEAKER 0 Uh And then again, remember that action potentials at this level when we're bringing them into the T-tubule, that's going to lead to a release of calcium from the sarcoplasmic
SPEAKER 1 reticulum. So if we're unable to send that signal and generate that sort of electrical signal to that rhyanine receptor, then you're not going to be able to generate an act or cause the release of calcium from the sarcoplasmic reticulum because again that electric signal is now not being sort of properly transmitted. Acid buildup, so this is something that I alluded to
SPEAKER 0 earlier. Again, when we're going through anaerobic glycolysis, we are going
SPEAKER 1 to be producing lactate and hydrogen ions. Uh, and again, remember, hydrogen ions or protons, they essentially drive the pH of something down to a more acidic level and when we become too acidic, A lot of
SPEAKER 0 the enzymes that are associated with energy production and things
SPEAKER 1 like glycolysis, they sort of become denatured, they don't function
SPEAKER 0 well, so then you sort of have an interruption of
SPEAKER 1 that glycolytic process which reduces the amount of ATP that we can generate. And then we also have a situation where uh the myofibrils become less sensitive to calcium as a result of an increase in hydrogen ions into the cell. So those would be your two ways that acid buildup is going to interfere and cause fatigue at the peripheral level. And then we also have inhibition of cross bridge cycling.
SPEAKER 0 So if you get a bunch of ADP and an organic phosphate.
SPEAKER 1 Uh, it sort of creates a situation that inorganic phosphate
SPEAKER 0 doesn't want to dissociate anymore because of the concentration gradient issue and then that is going to interfere with, um, that power stroke where we're again shooting off that inorganic
SPEAKER 1 phosphate to be able to pull actin in towards the
SPEAKER 0 M line. So that is going to be sort of your three
SPEAKER 1 main peripheral uh issues that go on with skeletal muscle
SPEAKER 0 and then moving from there into central fatigue.
SPEAKER 1 Uh, this is your, uh, like upper level fatigue. This is tied back to the central nervous system. So I think action potentials here uh and less so about the actual contractile machinery of the skeletal muscle. So just as a quick review or something that we may not have talked about as in depth in class, uh, this is sort of the process of Generating an
SPEAKER 0 action potential.
SPEAKER 1 So, You have, uh, pretty much this prefrontal cortex. It is all your like voluntary, uh, like I want
SPEAKER 0 to do this, I decide to do this, all that
SPEAKER 1 stuff is generated there, from there, from like a motor
SPEAKER 0 standpoint. That signal then gets transmitted to this motor cortex in
SPEAKER 1 the body, uh which then sort of processes and refines
SPEAKER 0 that motor signal for sending it down the spinal cord
SPEAKER 1 and all this stuff. Uh, from the brain into the spinal cord. All that stuff is called your upper motor neuron, OK? So, uh, again, you decide to do a movement, your,
SPEAKER 0 uh, motor cortex processes that movement.
SPEAKER 1 It's then sent out, uh, through an upper motor neuron. Um, and then eventually, once it gets to the, um, Periphery, again, like there's spinal nerves that innervate, all kinds
SPEAKER 0 of limbs and stuff like that. It'll synapse with that spinal nerve and then uh that's
SPEAKER 1 where it is being transferred from the upper motor neuron to the lower motor neuron.
SPEAKER 0 So right now we're talking all about upper motor neuron
SPEAKER 1 stuff right now. Uh, sorry, my voice is like.
SPEAKER 0 Going, but anyway. So, Moving from there, um, just know that.
SPEAKER 1 As a human being you are a very, very, very complex, uh, person and noting that almost, uh, you know,
SPEAKER 0 your, your central motor command in your brain is sort of your first, uh, step in the sequence of events that generates movement and our brains are uh very temperamental
SPEAKER 1 to uh tons of different physiological things, emotional states, um,
SPEAKER 0 motivations. All that stuff. So ultimately your brain is controlling the strength of that action potential. Um, so, uh, and here's some of the like factors
SPEAKER 1 that influence that. So if you're hypoglycemic, meaning you have low blood sugar, uh, just as a protective mechanism, you may not generate as high of a central motor command, um, because you're trying to conserve energy and your body is like, hey, I'm running low on energy, probably not a good idea to go full sun right now whatever activity I'm doing.
SPEAKER 0 Dehydration Same thing. If your body senses that your hydration status is not great, um, that can actually cause your blood to be more viscous, uh, and that can increase your heart rate because again, your blood is thicker, your heart is having to work harder to pump that blood.
SPEAKER 1 Um, so again, your body may decide, hey, uh, we're
SPEAKER 0 dehydrated, uh, and I don't want to enter into a
SPEAKER 1 very dangerous situation because again, maybe you won't be able to sweat as much to cool yourself either.
SPEAKER 0 So, um, Your brain will sort of say, hey, probably
SPEAKER 1 not the best time to again go full sand with this stuff.
SPEAKER 0 Motivation, this is a really big one. So if any of you guys have ever, I don't
SPEAKER 1 know, done like a powerlifting meet or race against a friend or you're in the gym and your gym crush walks in, uh, suddenly you become more motivated, maybe you're able to perform at a higher level. Uh, this is because your brain has decided, hey, Uh, this is a good time to really ramp things up. So you are getting a stronger, stronger signal sent from the brain down to the lower motor neuron, which is causing it to have increased excitatory effect and therefore increasing um sort of your performance.
SPEAKER 0 Uh allostatic load, we sort of talked about this earlier,
SPEAKER 1 but allostatic load is just talking about like to accumulated stress across multiple systems. Um so maybe during finals week, you think, hey, let me go to the gym and you'll notice that your performance is down. Uh, and this is again because your allostatic load is very high, maybe you're very stressed out and your brain again being as temperamental as it is, is probably not going to allow you to have a super high amount of Uh, performance for that day, uh, drug use, uh, certain drugs like caffeine, amphetamines, all that stuff can be very excitatory for, um, both your central nervous system and your peripheral nervous system, uh, because it can sort of increase your transmitters at both of those areas that would allow you to, uh, generate, uh, stronger action potentials or action potentials in, uh, greater susception, that kind of thing.
SPEAKER 0 And then we also have effort feedback, so um we
SPEAKER 1 could be looking at things like peripheral fatigue mechanisms like we talked about where we're talking about, uh, not only at the skeletal muscle where we have a high amount of like hydrogen ion accumulation that's uh causing the muscle to not function properly, but, uh, any of you guys that have ever Worked out or done like a set
SPEAKER 0 of 20.
SPEAKER 1 On, I don't know, like press, the failure or something like that or sprinted for a long period of time, you'll know that sensation of acidity is very uncomfortable and you have sensations in your body that are then feeding back to um the brain. That is kind of saying like, hey, this is what's going on here and then you uh you have this
SPEAKER 0 like level of perception of effort that is occurring across
SPEAKER 1 multiple physiological systems, you know, again related to uh respiratory rate or what's going on from a uh acid-based standpoint, sort of being picked up by like chemoreceptors that are then feeding back, um, that are again gonna tell your brain, hey, Maybe not do a full sentence because all these other things are out of whack or maybe you just get really uncomfortable and that causes like an emotional response and you don't want to push as hard and then you just voluntarily kind of stop sending that signal. So I spent a lot of time on the slide. A lot of that is probably information that uh is not necessarily out of the scope of this class, but just giving you a lot more context to, hey, this is what central fatigue is, again, it's fatigue or a lack of uh Sort of electrical signal being sent from the upper motor neuron or the brain level to the skeletal muscle. Um, so yeah, I just wanted to give that context.
SPEAKER 0 Whole muscle contraction.
SPEAKER 1 So, um, Sorry, that was gross. Um, again, allergies, but, uh, anyway, so something to know is that motor units, uh, all of the muscle fibers within a motor unit are going to be the same type. So they're all gonna be type 1 or uh type 2, what have you. Uh, but just know that like your entire muscle composition, so like say of your Hamstrings or I think the
SPEAKER 0 example we used in the um Class would be your
SPEAKER 1 calves, right? Your calves are composed of both your gastro and your soleus, um, but, uh, those are going to have a sort of distribution of fibers that are gonna be, uh, buried, right? So you're gonna have some fibers in there that are type 1 resistant to fatigue, and then others that are gonna be type 2 that are going to be very like powerful and things like that. And then the distribution of the fibers is going to be dependent on oftentimes like the function of that muscle. So like things like postural muscles, it's gonna be a lot more slow twitch. Uh, obviously, uh, because what you want them to be fatigue resistant, and then from like a dynamic like muscle action, so think like things like sprinting or jumping, so
SPEAKER 0 I like to think of the hamstrings, hamstrings are very,
SPEAKER 1 very fast witch fibers, um, so they can produce a lot of force very quickly and then they, um, sort of fatigue very quickly. So yeah.
SPEAKER 0 Control of muscle tension.
SPEAKER 1 Um, so this is a bit of a tricky concept to understand. So, uh, remember that your entire skeletal muscle is comprised of skeletal muscle fibers. So, and then if we think back to the Uh, load velocity, or sorry, force velocity relationship, we know that the highest amount of forces are going to occur with a low velocity contraction. And just to reiterate that load velocity curve is not talking about force equals mass times acceleration. It's talking about the force occurring at the fiber level. So the force that's occurring between the actin and mice and cross bridges. So you're going to have the highest tension for fiber. With the very slow, um, contraction concentrically. Um, so the reason for that is because again, those cross bridges take time to form. So the slower that you go, the more cross bridges can form, and then the more tension is gonna be available on those fibers. But the problem with that. Is that while a slow contraction speed um does uh Sort of increase the force on the fiber, um, it doesn't necessarily mean that a lot of fibers within that skeletal muscle, uh, are gonna be active. So when we're talking about fiber recruitment, we're talking about, um, tenement size principle. So if we remember, we're going to recruit our low threshold motor units first. And then they're gonna be recruited, uh, recruited cumulative, uh, wow, recruited cumulatively from low to high. So, uh, you know, when we're doing like really high intensity effort things, we're going to recruit low threshold and then as we start increasing effort, we still start at low threshold motor units and then uh we sort of uh stack uh motor units on top of that based on our effort level or demand of the exercise. So if we want to have the highest. Uh, level of mechanical tension within the muscle, we need two things. We need a high degree of motor unit recruitment again, which is going to be based on effort or lifting something really heavy, and then we need a slow concentric contraction velocity, um, so that again, uh, the amount of cross bridges that are formed can be maximized by that, uh, slow contraction velocity. So all this is to say, if I've totally confused you, I totally get it. Um, if you voluntarily like flex your bicep very slowly, you're going to have a high amount of tension on the fibers that are active, but we don't have a lot of fibers that are active because the effort is very low. Now, if you are to try to curl, I don't know, a very heavy dumbbell for you and the contraction speed is slow. Uh, but you're recruiting more motor units to be able to lift that very heavy weight. Now we have both a high level of motor unit recruitment and a high level of cross bridge formation as a result of that very slow speed. So that way tension is going to be maximized in the entire skeletal muscle. Anyway, my friend just had a baby, so he's texting me all this stuff. We, we need to chat, so. OK, moving into hypertrophy and atrophy.
SPEAKER 0 So, uh, there are a lot of models that have
SPEAKER 1 been put forth regarding hypertrophy. Uh, Brad Schoenfeld has a model that suggests that things like mechanical tension, muscle damage, and metabolic stress cause hypertrophy in their own ways. However, As more sort of research has come out, uh, metabolic stress, which again, if you guys, that just means sort of the metabolic byproducts that we sort of form, um. As a result of producing ATP to fuel exercise, some of those uh metabolites is what they're called. They're the byproducts might signal for some sort of cellular process that would increase cross-sectional area of the muscle. That's what it means when it says metabolic stress, um. And then muscle damage, uh, you know. That is fairly intuitive. When we lift weights, we do incur some muscle damage, although I don't want to spoil anything because that might be one of the slides coming up. I'm gonna talk about what that muscle damage is and what it is not. But um, as more research has kind of come out. Muscle damage absolutely positively does not produce skeletal muscle hypertrophy and neither does metabolic stress. The only thing that has been consistently shown over time to produce hypertrophy is a high degree of mechanical tension. Uh, so that is what is going to be triggering your, uh, skeletal muscle hypertrophy. And then When we're talking about, I don't know why this is metabolic activity, but uh if we're talking about atrophy, um, if you're not loading those fibers um with a mechanical load, uh, then they're gonna atrophy because of metabolic activity that's why, because again, uh, skeletal muscles are
SPEAKER 0 very metabolically active, um, they cost your body a lot
SPEAKER 1 of energy to maintain. So, uh, since your body wants to survive and be as energy efficient as possible, if you are not using the fibers, then your body will just essentially get rid of them. Um, atrophy occurs very, very rapidly. Um, we can see this in cases of bed rest or limb immobilization. So if you guys have ever broken an arm and you take the cast off and your arm is like, I don't know, like half the size of the arm that's unaffected, uh, yeah, you've lost a ton of muscle mass in the arm. Because you haven't been able to expose that arm to any level of mechanical tension. Same thing goes with bed rest. If you're just laying around in the bed all day and not even really, uh, moving your arms around or legs around against the forces of gravity, you're going to atrophy rapidly. Uh, something else that's kind of cool is that, again, this is kind of tied back to the size principle is that people that have never like Exercise at a very high intensity, literally have skeletal muscle fibers that have never been loaded in their entire lives and may never be loaded unless they do something that causes them to recruit them. Um, so, yeah, fun fact, so. Anyway, um, the other thing that can happen is, uh, if we have, uh, loss of innervation to a skeletal muscle, meaning it's not able to, uh, the, the neuron is not able to deliver an electrical signal to the muscle that would cause it to contract, um, then again, that muscle is gonna atrophy because it has no way of being activated. All right. Moving into the late onset muscle soreness.
SPEAKER 0 So, um, First thing I want to point out, we'll
SPEAKER 1 start down here is that it appears that eccentric contractions um are going to be sort of what caused the late onset soreness at a higher rate than concentric contractions, and recovery is gonna typically last 2 to 4 days, um.
SPEAKER 0 Yeah, so, uh, we used to think, or some people
SPEAKER 1 still say that the late onset muscle soreness and even mechanisms of hypertrophy occur because when you lift weights you get these micro tears and your muscle fibers and then, you know, that's what makes you sore. It's an inflammatory process and then uh you tear your muscle back or you tear your muscle down and then build it back up bigger and that's how hypertrophy occurs. And again, uh, I don't know, this has been rebutted and dismissed for I don't know, 20 to 30 years at this point. Uh, so anyone that is still saying this is very out of the loop. Um, yeah, so, uh, what is really happening when we have delayed onset muscle soreness is, as you guys should have down by now, um, one of the signaling molecules for skeletal muscle contraction is going to be calcium, uh, and again, remember it's start in the sarcoplasmic reticulum, uh, and then we uh sort of dump that into the sarcoplasma sarcoplasm, and then I don't want to go through that whole cycle. You guys should know that by now, but what you need to know is that while a lot of that calcium isn't pumped back up into the sarcoplasmic reticulate through that sarco pump, not all of it is, and so that residual calcium that's just kind of hanging out in the sarcoplasm. is not particularly good for the cell. So what we have is uh these proteases called calpanes, and again, this might be a little bit outside the scope. I'm not sure how in depth you guys went. This is just something that I find very interesting, uh, and something that you can like, I don't know, like some physiological knowledge on people. Uh, so yeah, uh, you have cowpanes that come to clear out that excess calcium, and some of that cow paine activity ends up damaging some of the myofibrils. And if you guys remember myofibrils are the contractile components of the skeletal muscle. Uh, once those myofibrils are damaged, uh, uh, your body will essentially get rid of them. Um, so it will go through this process called apoptosis, which is just programmed cell death and then you replace those old myofibrils with new myofibrils, and, uh, during that process, that also can cause an inflammatory response, um. And that is typically associated uh with uh the soreness. There's also Uh, right now, kind of hanging out with regards to, uh, maybe the muscle spindle nerve being damaged and that could also have a role in delayed onset muscle soreness, but I'm not really sure. Turns out it's pretty complex. Just know that your muscles are not torn down and built back up stronger and muscle damage, uh, you know, it's not because of, uh, micro tears, it's because of, uh, cal pain activity within the skeletal muscle clearing out calcium ions, uh, which is way more nerdy than just saying micro tears, but Yeah, it turns out physiology is complex, so.
SPEAKER 0 OK, we are finally through skeletal muscle for the most
SPEAKER 1 part. Uh, we are going to talk about some proprioceptors, but, uh, biggest thing I want to talk to you here, I'm not even, how long have we been live? OK, so I probably got another 30 minutes I can spend on this, um. So smooth muscle contraction, we talked about smooth muscle a lot in the early portion of the semester. Uh, smooth muscle, just think of things like digestive tract, uh, you know, your bladder and ureters, blood vessels, things like that. Um, again, that is a type of uh muscle tissue, smooth muscle tissue that, um, obviously needs to contract to sort of move products through your body. So, Uh, some unique characteristics of smooth muscle, you're gonna lack those myofibrils and sarcomeres. So remember that is what was giving skeletal muscle it's very, uh, striated appearance. So in contrast, smooth muscle is not going to have a striated appearance, it's gonna be sort of jumbled and um touted. And uh it does not have troponin. It does have ripamycin, but we are not uh sure of the role of ripamycin and smooth muscle. So next, This is how smooth muscle contraction works. Um, I'm going to pull up, I tried to insert a picture in the next slide, but my computer just wasn't letting me do it. So I'll try to pull up a picture and walk you through this because I think it's a lot easier to see from a visual standpoint, but know that calcium is still a signaling molecule for some muscle contraction. Uh, but know that there are two sources, uh, calcium with this. So you have a sarcoplasmic reticulum, which is much smaller than the one in muscle, and then you have, um, calcium that's coming from the extracellular space. Uh, again, think back to your ion concentration, stuff like that, salt and calcium covered banana, so calcium, extracellular ion. I'm just gonna keep saying that because it's, you know, useful. So. What ends up happening is calcium is going to come in and it's going to activate this calmodulin molecule, which is this, it's just a calcium sensitive protein, and that's going to form this calcium cowmodulin complex. From there, it's going to activate this enzyme called myosin light chain kinase, which is then going to phosphorylate uh myosin and allow it to bind to actin. So very, very different than, um, skeletal muscle contraction where you had the calcium coming in and you know, you have the troponin and yoin complex and then the myosin had been covered. Uh, this is uh ATP and phosphorylation to be able to. Uh, sort of have that myoin and actin binding, uh, relaxation. So if you guys remember, if we have a chinase that adds a phosphate, if you have a phosphatase that is going to get, uh, the phosphate off, so you have a myosin light chain phosphatase that's gonna come in, remove that phosphate from myasin, and then you will be in a phosphorylated state and actinomyosin will dissociate causing the relaxation of the smooth muscle. Uh, also of note, uh, smooth muscle does have some pacemaker cells, namely in your digestive tract, not everywhere, but essentially what you need to know about pacemaker cells is that instead of relying on the central nervous system to deliver that electrical signal action potential, uh, pacemaker cells sort of allow the cell itself to generate its own electrical signal or action potentials to be able to go through a depolarization event, um. And then what we see here is that the GI tract sort of has these rhythmic contractions as a result of the pacemaker cell activity. Yeah. Cardiac muscle contraction, this one's very easy. Uh, it's gonna be the exact same contraction mechanism as skeletal muscle. So if you know skeletal muscle, you know cardiac, uh, I don't know if I can remember in the past if there's a lot of uh questions on cardiac muscle contraction, but again, if you just remember that the contraction mechanism is the same as skeletal muscle, you'll be in good shape. But note that. Some key characteristics we talked about this early in the semester are those gap junctions. So remember gap junctions we kind of just talked about as like tunnels between cells that allow things to pass from one side to the next. Um, so in the case of cardiac muscle, these gap junctions are allowing that electrical signal to pass from one cell to the next and really allow the heart to contract a unit. And then also know that the absolute refractory period.
SPEAKER 0 Uh, so it's gonna be a lot longer.
SPEAKER 1 Um, the reason for that is because we don't want the heart again to be in an irregular.
SPEAKER 0 In uncoordinated um fashion.
SPEAKER 1 So as a result, we had this longer refractory uh period to be able to uh permit that from happening because if we didn't have that prolonged uh refractory period and we uh sort of Had this satanic contraction occur, which if you guys remember, titanic contraction is like your highest level of um Uh, skeletal muscle contraction, uh, that can, uh, cause, uh, irregular contractions and, uh, interrupted blood flow, which would not be physiologically a good scenario. And finally moving into muscle proprioceptors, so. Uh, we have a couple here. So we have muscle spindles and Golgi tendon organs. Uh, note that your muscle spindles are actually going to be located within the muscle itself, um. So you actually have two different kinds of fibers in your muscles. You have extrafusal fibers, which are the ones that are actual like the contractile fibers that we talked about, and then you have intrafusal fibers that are, uh, sort of going to be associated with your muscle spindles. Uh, and you can just think again, proprioceptive or sensory fibers is kind of how to think of this. Uh, and then when we're talking about muscle spindles, we're talking about, uh, namely responding to changes in muscle length in a velocity dependent manner. So if we stretch our muscle very quickly, you're going to have a very robust, uh, sort of response from that muscle spindle. Uh, the proprioceptive signal, uh, so we're going to send a signal to the central nervous system through gamma motor neurons. Uh, and if you remember, uh, when we're talking about skeletal muscle, we're talking about uh alpha motor neurons, so this is a different kind of neuron, and, uh, that signal is not going to go all the way up to the brain, uh, rather, that signal is just going to synapse within an interneuron in that spinal cord because again, it's a reflex, right? So reflexes need to be, uh, very quick, um. So as a result, uh, it's just a much more
SPEAKER 0 time efficient thing to be able to synapse in the
SPEAKER 1 spinal cord and then uh send that signal back out. So this is going to be what is responsible for that stretch reflex. Some of you guys may have heard of, or maybe you're noticing like, hey, when, uh, you know, you're lifting weights, if you pause at the bottom of something, uh. It makes the lift a little bit more difficult, and that's because some of that velocity dependent response from that stretch has dissipated. So, uh, typically the faster you can go down and control with a load, uh, the easier it is to come up, both because of, uh, sort of the contractile components of passive tension, but also you get a higher level response of the muscle spindle. And then moving into the Golgi tendon organs, these are going to be located in the muscular tendons junction or I mean, and that's just saying the tendon, right? If we remember like, you know. Muscles, uh, essentially kind of bottleneck into a tendon, which then inserts onto bones that cross joints and that's what allows you to move. So that's just sort of connective tissue associated with uh skeletal muscle. So, uh, and they are going to monitor total muscle tension, uh, and in general, Muscle spins are going to have an inhibitory uh sort of response to a very high amount of muscle tension, and the reason for this is because they're trying to prevent you from like tearing a muscle. So if you start lifting a load that is super,
SPEAKER 0 super way in excess of what you might be able
SPEAKER 1 to handle, and the Golgi tendon organ can determine that by monitoring the tension within the muscle, uh, it will just shut off. Essentially that muscle, uh, and cause it to relax, uh,
SPEAKER 0 to try to prevent it from tearing.
SPEAKER 1 Yeah. And then moving into the withdrawal reflex, uh, what we have here is you will have a painful stimulus. So I guess let me back up. So let's say that you're walking down the street and you step on attack, right? That's a very relatable thing or you step on a rock with a barefoot or something like that. Uh, this is kind of describing the phenomenon that happens with that. So you're going to have a painful stimulus or a
SPEAKER 0 threatening stimulus detected by nociceptors.
SPEAKER 1 On that leg And then what's gonna happen is that, uh, signal is gonna, uh, again be carried into the spinal cord and synapse there those inner neurons. And remember, inner neurons are just neurons that are located within the spinal cord. Then you're going to send a motor signal to the ipsilateral leg, which ipsilateral just means same side. So think the same uh like that uh is affected, right? So this like if you step on the tack with your right leg, uh, this is the signal that would be sent to the right leg.
SPEAKER 0 So you're going to activate at a very high level
SPEAKER 1 your flexors. So when we think about flexion, we're thinking about bringing things closer to the body and that should make sense, right? So when you step on a tack, you don't extend that leg further into the tack. That would be counterintuitive. That would, that would be injurious. So you want to uh pull that leg away. So think about like you want to uh flex your knee, flex your hip, uh, to be able to pull that leg away from that painful stimulus, right? Now because you are doing that, you're now going to have to have Your body supported on one leg. So, as a result, uh, your nervous system is also gonna send a signal to the contralateral leg, uh that is going to uh excite the extensors. So, uh, by exciting the extensors, um, again, uh, knee extension, hip extension, all that stuff, that is a position that you're gonna be on when you're standing. So if that is going to allow you to, uh, very easily support your body weight. Now, That's the obvious part. The next part is a bit less obvious, but know that whenever we are sort of contracting a muscle, you're always going to be to some degree uh contracting muscles on both sides of the joint. So whenever you are flexing your arm, like during a bicep curl, yes, your biceps are contracting, but your triceps are also contracting. Um, that is called uh coactivation. Uh, and typically, so you have an agonist, which is sort of your prime mover in that case would be the bicep and then your antagonist would be your tricep. You're always to some degree gonna be activating both the agonist, antagonist and antagonist. And the reason for that is because it is going to help you decelerate. Um, that limb and it's in range of motion to make sure that the joint stays protected. So in the case of an ipsilateral response, um, Again, we're going to activate the flexors, but then we're gonna also want to inhibit extensors. The reason for that is if you like if you were to just sit there and try to curl your arm, like flex your bicep and tricep as hard as you can, and while you're doing that, try to bring your arm very close, right? So when your triceps are contracting, it's trying to pull your elbow one way and when your biceps are contracting, it's trying to pull your elbow the other way. So it's kind of like this tug of war that's going on, uh, over control of that joint. So if you're able to inhibit the extensors, you're able to much, uh, at a much quicker, uh, rate, be able to pull that leg away because those muscles are no longer, uh, fighting for control of that joint. Same thing on the opposite leg, right? We want to inhibit the flexors to be able to quickly get into that single limb support on that other side. Uh, yeah. Wow, is that it? So it's 405. I've been going for 50 minutes.
SPEAKER 0 Uh, let's see, do I wanna go back and cover
SPEAKER 1 some stuff?
SPEAKER 0 So the next part of this is just um Gonna be rehashing some nutrition stuff, but I think I might just call it here and then pick up with an all nutrition and uh digestion and absorption, post-absorption review for
SPEAKER 1 the next one. I don't think it makes much. Uh, because again, that'd just be a very hard pivot. Um, so I think that's what I'm gonna do.
SPEAKER 0 I think I'm gonna call the review here. And uh next time we jump in, we are going
SPEAKER 1 to review uh just the things that we went over
SPEAKER 0 in chapter one, or not chapter one but exam one,
SPEAKER 1 and then we will then add that additional content on top of that.
SPEAKER 0 Um, again, I just ask that you guys work with me right now uh with midterms.
SPEAKER 1 I know that once I get through this week, things are going to substantially calm down for me, uh. We're actually, uh, one of our classes ends on Thursday,
SPEAKER 0 Halloween, which is gonna be super nice.
SPEAKER 1 Uh, so I am going to try my best to, uh, Had that exam review for you guys obviously Wednesday, nothing's gonna change about that. Uh, I will also do a final review session, um.
SPEAKER 0 I'll try to have that up by the end of the week. Again, I will cover everything from a nutrition standpoint and
SPEAKER 1 then, um, moving forward into the next exam, I will try to get us back on track with uh the weekly review sessions, although Uh, you guys have not been
SPEAKER 0 turning out to those like I would have hoped for, um, so it might just be better for me to just do these online, uh, that way there's less time constraints, and if no one shows up or very few
SPEAKER 1 people show up, uh, I can just kind of do this whenever I can get to it. Um, but yeah, uh, I hope you guys found this helpful and I will see you guys soon. "
"SPEAKER 0 All right, so this is the final part of exam three's content. Um, it's a lot, uh, I know it's a lot, um, but know that. I believe we talked about maybe the majority of the questions are going to be coming from the skeletal muscle staff. That is why we spent so much time on that during the exam review if you were there for that, um, and then. The cool part about this exam is, yes, it's a lot of content, however, um, this is your kind of second pass through a lot of this material. So again, we've kind of talked about renal, we've talked about, uh, digestion, absorption, uh, so we're really only adding, I don't know, maybe another 20% of new content on top of that stuff you already knew as well as all of the new, uh, information about, uh, muscle, so skeletal muscle, cardiac muscle, smooth muscle, all that stuff. So. We are gonna get into today's review. It starts here. OK, so as I just kind of said, um, we talked a ton about digestion, absorption early in the semester for exam one, that was mostly focused on, uh, sort of the transport mechanisms and applying those that we learned really early on, uh, primary active, all that stuff, uh, in terms of transport. So, um, now we are going to kind of review that a little bit, um, and you'll notice that I've really tried to, uh, bold or underline things that are most important and also adding in things that are, uh, new that we didn't really cover a lot. I'll try to draw attention to that because that is really where you should be focusing most of your time studying, uh, not to say that, you know, this other stuff isn't going to be showing up on the exam, but. You know, if you think about, well, I've already been asked to do this one time and then you know we're covering new additional content, I would bet that your best time spent is going to be used as kind of studying that newer stuff. So. Uh, these are our primary digestive organs. Uh, this slide probably looks familiar to you guys again. This was from the, um, either first or second review session, but I've kind of edited it uh to update it relative to the new information that we've covered. So as we know, we start in the mouth, that's how I eat if you eat differently, uh, I don't know what's up with that, but anyway, um, so again we have mechanical digestion going on, obviously chewing. And then um we have uh some uh enzymatic activity that is occurring in the mouth primarily when we're talking about carbohydrates, we're going to be talking about salivary amylase and then uh lipids, we're gonna be talking about lingual lipase. uh we are then going to swallow that food and uh that is going to enter into the esophagus, um, and then you're gonna have this smooth muscle contraction called peristalsis, again, uh, maybe. Kind of just making a connection here, smooth muscle. We talked about that and the different kind of contractile uh mechanisms that it uses compared to skeletal muscle. So, yup. And then uh the stomach. Uh, we are going to have an additional slide on the stomach coming up here, but main things here is just know that it is mostly a holding tank. It is sort of preparing that food to enter into the small intestine. So, uh, again, mostly a holding tank, but also we have some of. Mixture of gastric juice juices to form kyme and then we also have some hydrochloric acid there for a couple of reasons. Number one is we want to start the breakdown of proteins and then also if we have any kind of pathogens or bacteria that would be harmful to us that we don't kind of want making contact with the small intestines that stomach acid is there to kind of kind of kill off some of that stuff too. Moving into the small intestine, so again, this should be what we're thinking about when we're talking about absorption. This is the primary site of absorption for most of your micronutrients, uh, and again we're going to get into the specifics here, but just know that we're going to use enzymes from the pancreas, uh, and also bile that um that is made in the liver and then stored in the gallbladder, um, as part of this sort of uh absorptive process to kind of further break down the uh nutrients once they enter into the small intestine. And then also, uh, two new things that we are introduced to here in this kind of pass through is we have two hormones called Secretin or serotin that is going to be there to neutralize that stomach acid. Remember, um, sort of the epithelial cells within the small intestine are not going to deal with the very low acidity very well. They're not specialized for that. So as a result, we have a hormone there that is going to, uh, sort of allow us to help reduce some of that stomach acid. And then CCK, uh, this is going to be, uh, again when we have, uh, foodstuffs entering into the small intestine, uh, this is a hormone that is going to signal for the release of the digestive enzymes, uh, from the pancreas and then also bile from the gallbladder. Large intestine, not a ton going on here, but just know that you are gonna be, uh, absorbing most of your water and electrolytes from there and then that is also where the primary side of like your gut microbiome is not really uh in the context of this class, um, but you know, if you want to know more about that, I would highly recommend taking sports nutrition or advanced nutrition with Dr. Vaughn. Uh, you'll get a much deeper dive into uh these concepts with him. Uh, gastric emptying, this is a newer, uh, concept. I mean, obviously we know the stomach is going to empty into the small intestine, but this is going a lot more in detail here as to how that process kind of happens. So when we're talking gastric emptying, like I said, we're talking about food leaving the stomach. And entering into the small intestine and the regulation of that rate, your gastric emptying rate is going to be monitored by two sort of mechanisms. So we have feed forward and feedback. Uh, feed forward means, uh, something it's just like you're kind of anticipating something to happen. Your body is kind of preparing itself for an event that it knows it's going to happen, whereas feedback is like, hey, this is the state of something, so now I'm going to call back to something earlier in the sequence and maybe adjust it. So in the case of feed forward, we have two things here going on. So we have distension of the stomach, um, essentially distension is just kind of thinking about like if you're stretching something out, you're distending it. Um, so if your muscle becomes very full, I mean, obviously again we talked about it being a holding tank, so if it's full, then we know that hey, uh, it's probably a good idea to start, uh, allowing some of this food to pass into the small intestine, and then we also have uh gastrin, which is a, um, Hormone but again it's gonna respond to food uh kind of entering into the stomach. It's gonna enhance motility. Motility just means sort of the ability for that stuff to move through the stomach and then we're gonna also have the release of Pepsinogen and then calling back to that, we know that again proteins, we get a lot of breakdown or initial breakdown in the stomach. By the enzyme Pepin. So, uh, Pepcinogen, once it is released into the stomach, it is going to be converted into Pepsinogen, uh, uh, and it's gonna use hydrochloric acid to kind of uh aid in that process. And then moving into the small intestine, so this is going to be your feedback mechanism, right? So we're feeding back to the stomach, and essentially what we have here is, uh, essentially the macronutrient content that is entering into the small intestines. I think your fats, carbohydrates, proteins, uh, your absolute energy content. So, uh, how sort of energy dense that meal was and then the osmo osmolarity of the time. Uh, and if we remember like os osmorality just means, um, essentially how concentrated something is. So if it is a high concentration or high osmoality in the duodenum, that is going to slow the the rate of digestion and that logically should make sense, right? If it's more concentrated, there's more nutrients, it's going to take more time for the small intestine to be able to handle that. Um, OK, and then if you're thinking about, well, you know, how are we getting from the level of the stomach to the small intestine, uh, that is gonna be regulated by the same called your pyloric sphincter. Um, essentially it is like, uh, I don't know, a uh squeeze on a tube that is essentially uh kind of regulating the flow of uh food from the stomach into the small intestine. So again, Uh, signals from the small intestine are going to regulate the rate of the pyloric sphincter as well as from the stomach. So again, that is kind of what's being regulated when we're talking about these feed-forward and feedback, uh, sort of mechanisms. Um, and then if we have a slower release of time, uh, that is going to increase the, uh, time that that, uh, stuff is in the small intestine, right? So in other words, like if we just drop all of our food from our stomach right into the small intestine, uh, that would not be primarily good for, uh, absorption because again absorption, uh, it, it would decrease the likelihood that all those nutrients are gonna be absorbed, right? You have a higher chance of things, uh, maybe passing through the small intestine without being absorbed, um, which would not be good. Uh, so as a result, we want to have a slow, uh, sort of release from the stomach to maximize the chances that those nutrients will be absorbed. Uh, and then what you need to know is, uh, in terms of feedback we talked about macronutrients, energy content, osmolarity, all that stuff, know that fat content is going to be your primary inhibitor of, uh, the rate of gastric emptying. So if you have a very high fat meal, um. That is going to sort of slow the release of nutrients from the stomach into the small intestine the most. Couple of reasons for that. One, fat, very high energy. If we remember back to chapter one, fat is going to have 9 calories per gram compared to carbohydrates and protein, which has 4. And then also remember that we sort of have additional steps that, um. That has to go through, right? So remember it's not water soluble, we have to emulsify it with bile and then transport it across. So that's sort of an additional step. And then also know that it also is going to rely on passive diffusion mechanisms. So without the use of ATP, whereas, uh, some of the other uh micronutrients, so if we're talking about carbohydrates, we know that glucose and galactose are both going to use that, uh, sodium mediated, uh, transport, which is an active process. Turns out that when you use ATP. To transport that stuff, it ends up being a lot faster. And then when we also talk about protein, protein sort of follows that same role as uh those two that I just mentioned where we're using sodium and ATP to transport it across that membrane. So, um, again, fat, higher energy, uh, uses passive mechanisms and then you have additional steps so that should logically kind of make that connection in your head that, hey, if we have a high fat meal, uh, we need to kind of slow down the rate of gastric emptying to make sure that all that fat is able to sort of make its way across that membrane, uh, yeah. OK, so this is everything I just said just in picture format. Notice here gastrin and distension are going to be your feed forward mechanisms that I kind of outlined earlier. And then this up here is talking about all of the things that are sort of feeding back to that pyluric sphincter. So again, high high fat content is going to be your primary inhibitor protein also. Uh, tends to take a little bit longer to uh enter into the, uh, or slows the amount of gastric emptying, obviously energy content, and that you could just kind of scale that back to the relative size of the meal. Obviously, if you have a bigger meal, uh, it's going to slow the rate of gastric emptying. That's oftentimes why if you eat a big meal, uh, before like working out, uh, you probably aren't gonna feel too good. Uh, and then osmoality again, that's just concentration, particle size. I mean, all that stuff makes sense. I promise you're not going to be asked about particle size. Uh, OK. Secondary organs, so we again, this should be reviewed. Pancreas is going to be the primary site of both your, it's like a holding tank for your digestive enzymes as well as a producer of bicarbonate that we talked about is going to help uh sort of stimulate or I'm sorry, neutralize that stomach acid. Uh, and then we talked about the liver. Remember, your liver is what is going to produce your bile, and then your gallbladder is what is going to hold that bile, and then, uh, your gallbladder is gonna be stimulated during, uh, Uh, absorption and uh digestion to secrete that uh bile into the small intestine to help with fat emulsification. Uh, yep, all that should be reviewed. Uh, this is also a review, and this is just again making sure that we can understand the difference between the lumen side and the basolateral side. So remember your lumen side is kind of we describe that as the inside of a tube, so anything that is within the small intestine, it's going to be on the lumen side. Your basolateral side is going to be outside of the small intestine. Uh, so again, that's gonna be sort of the area of some some of that vasculature, um, namely like maybe your hepatic portal vein, for example, uh, because a lot of your nutrients, uh, once they leave the small intestine are going to enter into that hepatic portal vein and be taken back to the liver. So that's gonna be your basilateral side. But notice that, um, and not included here. is that you also, you have to pass through that cell as well. OK. So it's kind of like a sandwich, right? So you have your lumen side, you have your intracellular space, and then you have your basilateral side. We're gonna cover that early, but don't. Thing that you're just jumping right from uh one side all the way across without passing through the cell itself. All right, so again, I'm going to go through this pretty quick because again it should be review. Just know that when we're talking about carbohydrate digestion in the mouth, we sort of have search and all that stuff. This is all from chapter one and just as a reminder we do begin the breakdown of uh carbohydrate in the mouth with salivary amylase. Then again we go to the esophagus, um. And then again, I mean, these are just your sphincters. I don't think we talked about them too much, but just know that your upper esophageal sphincter is primarily responsible for preventing back flow from the esophagus into the mouth, and then your lower esophageal sphincter is primarily responsible for preventing backflow from the stomach into the esophagus. Um, and the stomach with carbohydrates, very little, uh, digestion going on again turning or turning to form thyme, that's pretty standard practice, and then you're gonna pass through that hyloric sphincter and then enter into the small intestine. Uh, and then this is a slide that we should probably spend a little bit more time on. So again, we have two sets of enzymes kind of going on here. We have pancreatic amylase. This is sort of your like big gross digestion of carbohydrates, so it's breaking down like the starches, right? So these like poly polypeptide, things that have multiple glycoytic bonds, and then we're going to get kind of down to the level of a disaccharide where your brush border enzymes are going to come in. And break those down just as a reminder of what those are, uh, so we have uh maltase, sucrase, and lactase and those are going to break dissaccharides down into glucose, fructose, and glactose. So remember your disaccharides are gonna be your maltose, sucrose, and lactose and um yeah, so. Again, just to know the enzyme name, you just take the OSE and change it into an ASE, and then you end up with your monosaccharides as listed there. Once we get into the actual um Sort of uh luminal side, uh, once we've kind of broken all those things down into their monosaccharide form, uh, we have two different kinds of transport. We have, uh, you have the SGLT1 transport, uh, which is going to use uh sodium gradient and ATP to transport glucose and galactose, um, across the luminal side to, uh, within the intestinal epithelial cell, whereas fructose ends up using uh facilitated diffusion in that glucose transporter 5. Transporter to end up with the intestinal epithelial cell. Uh, once they're in that epithelial cell, then they're all gonna leave and enter into that hepatic portal vein, uh, through that glucose transporter to, uh, yeah. This is just what everything I just said in a visual format just for a quick review. Again, here we have in the mouth, we have salivary amylase. Once we get to the small intestine, we have both pancreatic amylase that does that larger sort of gross digestion of starchy carbohydrates and stuff to break them down into disaccharides. That's when your brush border enzymes then take over. And then I turn them into their monomer or monosaccharide form. And then once we get over here, we're seeing that both sodium and I'm sorry, both glucose and glactose are using this SGLT mechanism which is using both sodium and ATP to enter into the intestinal epithelial cell. Whoops, where do I go? Whereas uh fructose is just using this um glucose transporter too, and then eventually once they all get in, they all are going to exit through. Let me just make sure I didn't misspeak there. Sorry, yeah, uh, fructose is using glucose transporter 5, and then once they are in, then they are all going to use um glucose transporter to to exit the epithelial cell to that basolateral side into that hepatic portal vein, and then from there they go to the liver. Fat, again, we talked about this. I'm gonna fly through this lingual light pace. Uh, is going on in the mouth, uh, in the stomach. You also have the inclusion of lingual lycopase, which is kind of still doing a little bit. And then we also have gastric lipase, which is gonna mostly focus on things like short and medium chain fatty acids, uh, and then from there you're going to enter into the small intestine as a result of passing through that pyloic sphincter. And I want to spend a little bit more time on this now because again this is sort of your big picture for absorption. So remember fats are not going to be water soluble. As a result, we have to emulsify them in bile to kind of prepare them for enzymatic activity. So first thing we have is we have sort of this fat globule. You have um. Bile enter into the common bile duct. Again, remember that's coming from your gallbladder, then bile is going to enter into the small intestine into that duodenum region and then uh from there it's gonna emulsify those uh. Fat globules into their fatty acid form so that way that um pancreatic lipase can come in and start uh sort of breaking those things down and then you end up forming a uh something called a mice cell. Uh, so again my cells are going to be composed of monoglycerides and free fatty acids, um, and again, note that the my cell sort of acts as a fairy, so it's gonna kind of gather those fatty acids up. It's going to take them to the uh. Brush border, which again is just uh the uh sort of luminal side of the intestinal epithelial cell. Uh, I'm sorry, luminal side, yeah, yeah. Anyway, sorry, I don't want to confuse you guys because I have a picture coming up that we're gonna cover all this in again. But it's kind of it's, it never enters into the cell itself. It's just dropping those fatty acids off and then going back, circling back, uh, within the luminal side, picking up more fatty acids and then it's kind of going through this process. Once you are inside of that intestinal epithelial cell, you end up forming what is called a ylomicron, um, which is then what is going to exit the uh. The intestinal epithelial cell to, um, it can either go one of two ways, if it's a large colomicron, uh, it can, uh, it's gonna have to go through the lymphatic system. If it's a smaller one, then it can also enter into this uh hepatic portal vein. So Again, this is essentially everything I just said. uh, so what we have here is uh not shown is that fat globule but you see up here we have bile coming in that is going to again break down that fat globule into a state where you have uh that pancreatic lipase can come in and start uh sort of breaking that down into fatty acids. From there you're gonna form a my cell, uh, which is going to. Uh, act as a fairy. So what we see here is you have a mice cell formation coming over here and then they're just dropping off these individual fatty acids. From there you're coming down here and forming a klomicron, which is in leaving the intestinal epithelial cell and entering into the lymphatic system through the lactteal. On the other hand, if we have a small chain or short chain fatty acid. Uh, or medium chain even apparently that is just going to cross over. Uh, we're not going to form it into the k micron and we're just gonna have free fatty acids that are going to be flowing through the blood and note that again remember fat is hydrophobic, meaning it does not like it does not play well in water. So as a result, we have to have some sort of protein transporter to be able to kind of take, uh, I guess make that uh fatty acid, uh, what am I trying to say? It kind of serves as a raft, right? So like it's trying to transport that it allows that fatty acid to transport through the blood. In the case of these fatty acids, it's going to be bound to albumin, which is again just your protein uh protein transporter is going to carry it through the uh plasma. Protein very quick, uh, nothing really going on in the mouth, and then once we get to the level of stomach, remember we talked about uh hydrochloric acid breaking down, uh. I'm sorry, converting uh Pepin into Pepsinogen, um, and then you start to break down some of that protein, uh, that is sort of, uh, you know, that's your macronutrient that is sort of undergoing the most, uh, I guess, breakdown in the stomach. Pancreatic enzymes, once we get into the small intestine, again, the biggest one that you need to know here is probably trypsin, but note that there are several, right again, think about how many amino acids there are in proteins relative to things like, uh, you know, your monosaccharides or your fatty acids and things like that. So there are going to be way, way, way more enzymes specific to proteins than the other two micronutrients and it would be. You know, I don't know, that would be a week's worth of lecture to just learn all those, and that makes me want to slam my head against the wall, so I'm glad we don't have to do that and I don't have to remember it and then teach it to you. So again, proteases, that is gonna be sort of your gross terminology. If I were to know one, I would know trips and, um, and just be able to kind of recognize that by name. And then moving into the lumen, uh, side transport again like we talked about amino acids, so we have, uh, your glucose and your lactose, we're gonna use that sodium dependent uh active transport mechanism, uh, same goes for amino acids, uh, and then again amino acids, they're gonna use a very common, uh, sort of pathway as uh I think they just use facilitated diffusion to, uh, yeah, to or active transport apparently, but just know that they're gonna exit and enter into that hepatic coral vein and go to the liver. This is a gross slide for you to compare and contrast all that stuff. uh, if you want to pause it here, I'm not going to rehash everything because we already have a lot of content to cover, but um, yeah, I, I think this is very useful just to be able to kind of see, OK, well, what's going on here, um, uh, and kind of being able to compare and contrast all those things. All right, so postcranial period, I'm gonna take a sip of water real quick actually before I, yeah. So this is still in your absorptive phase, but this is like post feeding, right? So at this point we're out of the small intestine. This is sort of your newer content that we haven't covered as much. But we're going to be talking about carbohydrates now, namely glucose, and the reason for that is because, yes, if you remember, hey, we have 3 monosaccharides, we have glucose, fructose, and galactose. Well, we convert fru fructose and galactose to the uh in the liver back to glucose. We don't. You know, you've never heard of blood fructose level levels or blood galactose levels. That's because we just convert all that stuff to glucose in the liver. So, uh, yes, what you have heard is correct, no matter what sort of carbohydrate you eat, uh, it all is going to end up as glucose, um, at some point down the line. Fun fact. So from there we can do a couple of things with glucose. Uh, we can store it as glycogen, which we've talked about, uh, and that it's gonna either occur in the liver, the liver or the skeletal muscle, uh, and that is gonna be, uh, primarily regulated by glycogen synthase. So, uh, after you eat a meal, um, that glycogen synthase enzyme is gonna be very active so that we can then take that glucose and store it as glycogen. Uh, we can also take that glucose and convert it into fat, so we can, um, either by way of sort of forming that glycerol backbone for fatty acids or we can convert them. Into uh fatty acids in the liver adipose tissue. This process is called de novo lipogenesis, just as a fun fact. So, uh, while we can do this, uh, we don't really see it done that often, uh, particularly if you eat just a normal amount of fat in your diet. Uh, there are circumstances to where maybe if you eat a very, very, very low fat diet and you have a very high carbohydrate. Intake that you will end up uh going through this de novo lipogenesis process more often, but also know that, and this is just sort of a pet peeve of mine is people are like, oh, carbohydrates make you fat, you know, you can convert it to fat blah blah blah. It's like, yeah, all that's true, but Your net amount of weight gain and weight loss is all going to be dependent upon your caloric expenditure. And just because these things do happen, you have to always look at physiology over the span of not just like a, a snapshot in time, right? Because we know that like for instance, after a meal, our insulin goes up and that's a storage hormone. So yeah, we bring in a bunch of glucose into the cell and then as we're seeing here, some of that can be stored as fat or you know, we might be also bringing in protein and stuff like that and it's like, well, that's just a snapshot in time, right? And. We know that homeostasis exists, so people never talk about glucagon. It's like, OK, well you're in this postcranial state, you know, you store all this stuff. Well, as soon as that event is over, you start entering into a catabolic state in which we have things like glucagon kind of pulling that blood sugar back out. We also have fatty acids being released from their cells so that we can stay alive as a result of um being able to utilize those for metabolism. So never, uh, I guess fall for the trick of Just taking a snapshot in time of any sort of physiological event and then trying to extrapolate that out over time because as we learn with homeostasis, almost every hormone in the body that we have has something that counteracts it and not in the opposite direction so that we can maintain homeostasis. Uh, and then again what ends up happening is if you have a net sort of anabolic signaling relative to fat, then you will start to gain body fat. However, if you have a net catabolic signaling or breakdown of fat, then you'll start losing fat. But it's not like an all or none switch. You always go through. No matter what, you're always gonna go through periods of anabolism and catabolism through the day and then your net is, uh, sort of what ends up being important. So that was a side rant, but I just feel like that's something that you all should know, uh, for the three people that maybe watched this, uh, you're welcome. Uh, anyway, so. Uh, that sort of sums up this and again, just to know, I, of course, we talked about energy metabolism. So again, glucose obviously is sort of your first, uh, metabolic sort of uh. I don't even know what to say. It's what enters into a glycolysis is what I'm trying to get at. I just blew all my cognitive bandwidth on explaining that other thing, but yeah, anyway. OK, and then when we're talking about lipids, lipids are going to have a different kind of system. Also know, sorry, just real quick that all again remember everything once it leaves the small intestine is going to go back to the liver through the hepatic portal vein, always, always, always. Anyway, moving on, uh, lipids, so lipids are um sort of special here. So you have uh first pass metabolism and second pass metabolism. So as we talked about, uh, those ylomicrons are gonna go through that lymphatic system and into the bloodstream. Uh, from there, they are going to do a first pass where they're gonna drop off some fatty acids into adipocytes. Uh, and they're gonna be sort of unloading them, uh, with the wiper protein lipase, um, and it just I would commit that to memory that, that, uh. Enzyme, uh, again, remember, an easy way to remember that is like a lot of times when we're talking about uh fats being transported through the blood, they're either gonna be bound to albumin or lipoproteins, um, like for instance, like maybe you've heard of LDL or HDL cholesterol, that stands for high density lipoprotein and low density lipoprotein. So, um, Again, remember those lipoproteins are the are the rafts, so we're trying to unload that uh fatty acid from that raft. So we need a lipoprotein lipase, so it's cutting off the uh fatty acid from that lipoprotein to be able to get it into the cell. That's kind of the best way to remember that. And then moving from there, uh, that remnant yom micron, uh, because remember it is now sort of incomplete because uh it has dropped off some of those fatty acids that's going to be transported back to the liver. Uh, and then from there this is sort of the second part of this. Uh, these kind of microns are then converted to this very low density lipoprotein in the liver which is going to make that second pass. So after it's converted at VLDL, it's going to then exit the liver and travel through the bloodstream and then make contact with even more cells, adipocytes, or skeletal muscle, and yes, that's not a typo, we store fat and skeletal muscle. Uh, namely our type 1 fibers and type 2A, because again it is very convenient because again when they have a high aerobic capacity we know that we're going to use more oxidative metabolic pathways and if we remember that it is going to be dependent on the supply of fatty acids, so it's very convenient to have a little bit of intramuscular triglyceride storage uh to kind of support that metabolism. Um, but yeah, and again, we're using that lipoprotein uh lipase to be able to uh unload that stuff. And then for protein, uh, again, I would be very surprised if you were asked about this, but just to cover it a little bit, know that again, remember that we are going back to the liver all the time when we leave the uh. Small intestine goes through that hepatic portal vein and we end up in the liver and then with proteins we have to do this process called deamination essentially if we remember back to uh sort of our I guess building blocks of protein, we have nitrogen, uh, so that nitrogen has to be removed before we can do anything else with that protein, and that is called the urea cycle and then uh, yeah, so essentially you're just chopping off that nitrogen to space and then moving in from there, we have protein utilization, so. Uh, the carbon skeletons of the deaminated proteins can be used for energy, and I would just note that I would, this can happen right the same way that we can convert glucose into fat. However, this is going to be a very, very rare situation where maybe we're in like a starvation mode and we are just have a ton of metabolism going on. We have very low food. Uh, then we can uh sort of break down our own muscle mass and use some of those again, uh, amino acid skeletons to form new glucose, but that is going to be under very rare, um, sort of. Situations and even more rare than that would be the conversion of uh proteins to fat. So um again in terms of functional roles of protein, they're vast. You guys should remember that from early on in the semester. I mean, yes, like they're obviously components of our skeletal muscle, but they also act as transporters in the body. They play a role in um like our polypeptide hormones. All that stuff is dependent on protein intake and uh having adequate amounts of amino acids, so. Uh, glucose post absorptive, uh, here. So this is sort of just kind of talking about like hey where can this stuff go and like you know what's it going to do. So obviously we have a blood glucose level that is sort of a part of metabolism. So some of that glucose is just going to kind of hang out in the blood to be able to support central nervous system function. And then when we're talking about the regulation of blood glucose again, some good review here, we have insulin which is going to lower blood glucose by increasing the amount of glucose in the cell. I see you guys getting tripped up on this pretty often because you think, oh well, insulin, we're increasing the amount of glucose, but remember that's occurring in the cell. We're taking it from the blood, decreasing its supply in the blood, and then pushing it into cells. Glucagon. On the other hand, remember that's like the flip side of insulin. So glucagon is gonna raise blood glucose by stimulating uh glycogen breakdown and that is really only gonna be happening in the liver. So the reason for that is because um Just as a review, if we remember that once we get that glucose into the skeletal muscle, uh, we immediately convert it to this thing called glucose 6 phosphate. And if you guys remember back to metabolism and uh glycolysis, that is the first step of glycolysis, but know that um. That is the first step of uh sort of trapping glucose within the skeletal muscles so that it can't go back the other way. From there we can convert that glucose 6 phosphate into pyrubate or lactate. Again, I'm not going to go through all of glycolysis for the sake of time and my own sanity, but um, yeah, so you end up forming either pyruva or lactate. Pyruva would be under aerobic conditions, lactate under anaerobic conditions, uh, but Note that the difference here is that when we're talking about the liver, uh, we can get through glycolysis or we can convert it uh glycogen stored in the liver back to glucose because um The liver has an enzyme called glucose 6 phosphatase, so that is essentially going in the opposite direction where we're going from glycogen back to glucose, and it's only an enzyme that is found in the liver. So in that sort of situation, then we're going to have a release of blood as a result of glucagon activity, activating that glucose 6 phosphatase enzyme and allowing blood to go back from the level of the liver into the blood to maintain uh blood glucose homeostasis. So, yeah. Take a sip of water. OK, so this is sort of talking about energy, and that was more of an energy mobilization slide before, by the way, this is also energy mobilization uh relative to lipids. So when we have a situation where we have uh metabolic demands uh by the cells, which is technically all the time if you don't have metabolic demands you're probably you are dead. But um, so anyway, so this is talking about how we're getting from the level of triglycerides down to fatty acids once they've been stored within a cell. So we have um Sort of 3 enzymes here that are going to be breaking down each sort of fatty acid from that cholesterol backbone. Your first one is going to be um your adipose triglyceride lipase, that's gonna get rid of that first fatty acid. From there we have hormone sensitive lipase, which is going to get rid of that second fatty acid, and then your monoglyceride lipase is going to be released, um, and sort of, uh, you, you're only gonna be left with the cholesterol backbone at that point. Uh, from there, the glycerol backbone can be transported to the liver where it can be converted to glucose, uh, as you guys have probably found out by now, uh, glucose is terribly, terribly important for us. So, uh, you know, we have that glucoogenesis process in the liver that can sort of convert, uh, glycerol backbones and uh just various other metabolites even like lactate and uh again amino acid skeletons and glucose. So glucose is super duper important for us, so. That's what we can do with that glycerol backbone, and then also just as a reminder here, remember fatty acids are not going to be soluble in the blood, so we're going to need a protein transporter. The protein transporter in this case is going to be albumin, which is going to be able to transfer the lipids through the blood and deliver them to cells. Uh and then, yeah, as we talked about 1 1000 times now, again, it's gonna be uh delivered to cells to support aerobic metabolism. This is just kind of uh talking about insulin here, what is stimulating insulin. So and we, we have in the top left here, we have sort of things that are showing, uh, uh, these are going to be things that are causing the release of insulin, anything in green. So again, if we have an increase in plasma glucose levels following a meal that is going to stimulate the release of insulin we see here that it's gonna make contact with receptors that are sort of uh in the pancreas cause the beta cells. Uh, also, if we have an increase in, um, Uh, amino acids, again, uh, insulin is also sensitive to amino acid release, which is why the immunization of insulin is stupid. Uh, I mean, yes, insulin can cause some problems, but it's not like the thing that we all need to be terrified of. It's actually very helpful because it helps you get stuff into cells where they can actually do stuff. Um, and then in the case of parasympathetic activity, remember that's your rest and digest that is also going to promote, uh, insulin sensitivity just as a result of, again, you're in a post feeding window that is when that division of your nervous system is going to be higher. I note that a lot of these things are going to be interlinked. It's not like the parasympathetic, uh, nervous system is gonna be acting in isolation more so it's responding to um. Again, eating a meal, you have various feedback mechanisms to the hypothalamus that are saying, hey, we just ate a meal. Let's sort of crank up this division of the nervous system. And then when we look over here, we see sympathetic activity in green. However, we have this plasma epinephrine in red that is saying that epinephrine is going to decrease the amount of insulin being released and the reason for that is we remember insulin. I'm sorry, epinephrine is a fight or flight hormone, so we're in that case going to want to be able to mobilize a bunch of blood glucose. So rather than shuttling it into the cells where it already is, we're going to want to go the other way where we're taking it out of cells, namely the liver, so that we have a higher amount of blood glucose that way we can have higher uptake of, um. Uh, glucose into the cells if we need it, and we didn't really talk about this too much, but also know that there are multiple ways that you can get glucose inside of cells that are sort of not related to insulin. You have another glucose transporter called glucose transporter 4, that seems to be activated by the release of calcium within muscles, uh, so that's one of the reasons that exercise can really help with, um, uh, sort of. Blood sugar regulation, stuff like that, it's because when we start having uh the release of calcium within muscles, it causes that glut4 to come to the surface of the cell membrane and allow for more glucose to enter into the cell. So again, insulin is just one way that we do that and again it's gonna mostly be active after a meal. On the other hand, We look over here and we see all the effects of having a high level of plasma insulin. So, and this is specific to each tissue. So in the muscle we're going to have an increased glucose uptake. You're going to have a net glycogen synthesis rate, meaning that we're going to be storing a higher amount of glycogen, which makes sense. You're going to have a higher amount of amino acid uptake and a higher amount of protein synthesis. Again, protein synthesis is very good for us. That's how it literally, you know, one of the mechanisms that we use to build muscle and note that insulin is playing a strong signaling effect for that outcome. Moving into adipocytes, we have an increase of glucose uptake into the adipocyte, and we might also see a net increase in triglyceride synthesis again, uh, maybe not as a result of glucose directly, but yeah, and then when we have the liver. We're going to see a decrease in gluconeogenesis because um essentially we already have enough glucose in the blood, uh, so, and we're trying to get it into cells, so we don't need to make more in the liver right then. We're going to have net glycogen synthesis, again, just like skeletal muscle, net triglyceride synthesis and then no ketone synthesis. Uh ketones are kind of outside the scope of this class. Uh, you might learn more about that nutrition. Um, but yeah, and then when we have a lower amount of plasma insulin, everything that I just said is just gonna go in the opposite direction. OK. So, uh, for instance, we're gonna have decreased amount of glucose uptake, um, in the skeletal muscle, uh, breakdown of glycogen, breakdown of protein, all that stuff. So if you know one, you know the other, but I, I would much rather you focus on understanding the actions of insulin and just knowing that when, hey, when insulin is low, that it's gonna just be pushing in the opposite direction. And then when we're talking about glucagon, essentially we're going to have to activate glucagon when we have a low amount of plasma glucose as indicated by this sort of figure over here. Uh, essentially we're going to have alpha cells in the pancreas that are going to detect this and secrete glucagon, and then again as a result of secreting glucagon, we're going to have a higher amount of glycogenolysis. Remember, glycogenolysis is a process of breaking down glycogen, right? We talked about about lysis being like cutting something. Uh, we're also gonna have a higher amount of glucomiogenesis because again we're trying to support um. The blood glucose levels. So as a result, if we can make some more uh glucose in the liver, that's going to be helpful. And again, don't worry about ketones, uh, and then as we see these are sort of your end products which is gonna be an increase in plasma glucose levels and then over here this is just kind of showing a little bit more of the effects of um sort of epinephrine's actions on uh sort of mobilizing glucose. Again, when we talked about epinephrine, fight or flight. Uh, we're going to have an increase in glycolysis again to be able to get blood into the, into, I'm sorry, uh, glucose into the blood, uh, and essentially all the same things are going to apply over here. We're going to be mobilizing nutrients. So again, glycogenolysis is going to go up, gluconogenesis, and then also lipolysis, which is the breakdown of fat into fatty acids. And then down here this is our table. This is sort of talking about all of our main regulatory hormones with regard to how their effects are on glucose, so. Again, glucagon and gluconeogenesis, those are going to be only acting on a sort of glucose. So again, glycogenolysis is going to go up, gluconeogenesis is going to go up, and then in the case of epinephrine, this is not going to necessarily act on just um glucose. We're also going to be immobilizing some fat here. um, so again lipolysis is going to go up, all these breakdown sort of processes are gonna go up and then with cortisol. We're going to have gluconeogenesis and lipolysis as well as the inhibition of glucose by muscle cells and the adipose tissue, and then the same thing can be said for growth hormone. Uh, this is sort of a, we had a whole lecture on this, but honestly I don't really expect there to be too many questions on this, um, other than just very basic level knowledge, um, just in terms of being able to differentiate between resting metabolic rate and basal metabolic rate. So basal metabolic rate, this is going to be your absolute lowest level of metabolic activity. Uh, the slide says here it's a minimum energy required for essential physiological functions at rest, measured under very strict conditions. Uh, and then typically measured in controlled environments where an individual is awake in a reclined position and completely at rest. Uh, another way to think about this is like if you were, I mean this is just like what is needed to absolutely keep you alive. Um, that is gonna be basal metabolic rate, and then resting metabolic rate is gonna be like, OK, let's have it, uh, your basal metabolic rate, and then also allow for some, uh, very like. Uh, movements that like maybe a very sedentary person would go, right? So we're not talking about exercise or anything like that, uh, but we may be talking about like the thermic effect of food, but uh it's just less restrictive, um, to be honest, uh, I don't really Like what am I trying to say here? The they're not too different and this is more of just like a, you know, like basal, this is more like for research terminology outside like nobody that you're ever gonna encounter uh hopefully unless you work in a hospital is gonna be solely relying on their basal metabolic rate, uh, and then resting metabolic rate, it's gonna be far more applicable to like your general, um. Populations and then just know that your total metabolic rate is going to be the sum of both your resting metabolic rate, your thermic effect of food. So again, remember that when we eat uh food, uh, we go through all that stuff we just discussed. Uh remember there's some ATP involved, uh, some body temperature uh increases as a result of that energy and stuff like that. So, uh, yes, uh, eating food actually requires energy to be able to sort of, um, The process and store. So this is why a lot of people when they enter into a calorie surplus, maybe they want to gain some weight and they increase their calories. Um, they may not gain weight at the rate that they were expecting because even though they've increased their calories, um, a lot more energy because again they're eating more food, there is a higher thermic effect of food, so that's kind of offsetting some of that surplus. And then you have the thermic effect of exercise. This is fairly straightforward. I mean, I think everyone knows that when you exercise your caloric expenditure, therefore metabolic rate goes up. um, so yeah, just know that the sum of sort of your total metabolic capacity is going to be resting metabolic rate, thermic effect of food, and then thermic effect of exercise. All right, let's see how I'm doing. How am I doing on time? Does you say? I, I have no idea how long I've been going, but I feel like this is a lot of content, uh, and I'm gonna have another sip of water, uh, and then we're gonna finish up renal physiology, and then that will be that. Uh Sorry, give me one sec. I check my phone real quick. Wow, I've been going for Almost an hour, if not an hour. Uh, that's crazy. So anyway, getting into renal physiology, uh, and again I guess this is gonna be a little bit of a longer review session because of the amount of content, but anyway, renal physiology, uh, this should be again some review, uh, just know that. Uh, when we're talking about renal physiology, we're going to be talking mostly about the kidneys, and then these are sort of your main 10,000 ft view function of the kidneys. So we're going to be looking to remove waste. Remember when we get through metabolism, we produce these things called metabolites that are just sort of byproducts of metabolism that really don't serve us any use, so we get rid of them through the urine. Uh, we also are going to be regulating water balance. We'll go into about as much detail as you could ever want on that in a minute. And then also moving from there, uh, acid base balance, we're going to talk about that a little bit, uh, yeah, and then hormone production. Uh, two things, the biggest ones are gonna be erythropoietine, which we're not gonna cover, uh, yet, that's gonna be in the next chapter, but we are going to talk about renin. OK, so This is all the way back to again the first exam, so we're going to be talking about glumellular filtration rate. So again that is just the rate at which your body is sort of filtering your blood uh through the glomerulus and through a nephron. So it, yeah, I think your body ends up filtering your blood something like all of your blood like 32 times a day, pretty crazy. So blood is going to enter into this aerent arterial and enter into the scmulus, which is a very high pressure system which is taking your blood, pushing it through all these sort of very, very high pressure capillaries, uh, and then uh it can either go through the eerent arterial where it's gonna just enter back into sort of, you know, your uh just normal blood supply, or you're gonna be pushed into Bowman's capsule and then that's sort of your like first stop for uh this sort of um nephron. Uh, of noting, uh, and something new here because again these are all the same slides that I use just updated with the new content. Is that when we're talking about the apher and arterial where things are coming in, we have these specialized meanna receptors there called juxtalomerular cells. Um, which are there to produce renin, uh, as a response of, uh, sort of blood pressure. So again, remember mechanic receptors, they sort of detect uh mechanical tension, stretch, things like that. So, uh, these have specialized, uh, cells there again juxta glomerular cells that are gonna, uh, essentially if there is a very high amount of blood pressure there and therefore like distension of that blood vessel. Uh, you're not gonna be wanting to produce a lot of renin, whereas if there is very little distension there, you're gonna want to have, uh, renin activate because that is going to increase your blood pressure. We'll get into that in a minute. But again, remember things leave the um. Uh, glomerulus, if they are not pushed through uh Bowman's Castle through the earin arterial, yeah. I just realized that this part of this is covered up, but yeah, you get the point. So again, we just talked about all this stuff. Aerent is where it enters, eherent is where it leaves, uh, so and then um just remember that 80% of the blood that is going to enter into that glomerulus is going to leave and then 20% of that is then going to enter the nephron and then of that 20%, 19% of that is going, uh that sort of filtrate is going to be re-entering the bloodstream. OK, so functions, uh, this is your proximal convoluted tubule. We're down here. Um, so again, remember we talked about the Satan in chapter one, but we have essentially, uh, a lot of sodium going to be reabsorbed water, uh, because of its sort of following, uh, sodium's concentration gradient. Glucose and amino acids are gonna be reabsorbed, uh, uh, because again, those things are typically very useful to us and then bicarbonate is also gonna be reabsorbed to sort of regulate that acid-base balance. And then in terms of secretion, remember when we're secreting things, we're moving from the level of the perittubular capillary, which is that um. Sort of venous system that is wrapped all around the uh nephron. So we're gonna be moving from the tubular capillary into the nephron, and when we're talking about reabsorption, we're talking about moving from the level of the nephron back into the paratubular capillary. But we're gonna be, uh, wanting to get rid of those hydrogen ions and other waste products like ammonia that we talked about. Remember we talked about, uh, deaminating and getting rid of that nitrogenous space, uh, through that urea cycle that ends up forming, uh, ammonia. So now you have more context for that if you were kind of confused about that early on. Transport mechanisms, um. Again, we talked about this a lot early on, uh, so you're gonna have sodium ions are gonna be. Sort of uh co-transported, um, And then you're also gonna have uh the actions of the sodium potassium pump to be able to push that sodium across. Uh, glucose and amino amino acids, again, we're gonna see a coupled transport with that SGLT1 transporter. And then when we're talking about water, again, it's gonna use aquaporins and sort of that osmotic gradient to be able to go across like we've talked about before. Uh, bicarbonate, again, I don't want to spend too much time here. Uh, it might be worth your time to go back to one of those earlier review sessions. Um, again, there is just a lot of stuff going on here with this carbonic anhydrase sort of reaction. Um, I'm not sure if you'll be asked to do this again, but if you are, um, I would go back and maybe review that video. But just know that essentially what we're doing is we're taking bicarbonate, we're disassembling it on one side of the cell and then reassembling it on the other, uh, and that is going to be done through the use of that our carbonic anhydrase uh reaction. So, yeah. And then you have your descending loop of Henley, this is your concentrating where we're having sodium leave. Remember you have both active and passive, uh, regions of the lupa Henley. Uh, this thin region is where we don't have any, uh, sort of mitochondria. So all the the uh transport mechanisms there are gonna be passive. And then, uh, when you have the thicker filament or, uh, sorry, thicker, uh, region of the tubule, uh, you can have a sort of ATP uh and uh active transport of sodium there. And then when we are in the thick filament, this is just what I just said, so again, you're gonna have that sodium potassium pump, uh remember this is sort of your uh diluting. Hang on, let me make sure I'm saying this correctly. Yeah, sending is diluting, so, uh, that is where we're gonna be getting rid of um. Sorry. I say absorbed. Yeah, so it's diluting because it's taking sodium out of the filtrate. That's why I couldn't make that connection on my head for some reason. Distalcombuvoluted tubule again, this should be reviewed, so I'm just going to kind of point out the newer content. You have your maculate denza, which is a chemoreceptor, meaning it's sensitive to like Uh, ions and things like that. Uh, so you have, uh, that is kind of hanging out in that distal convoluted tubule that is going to be detecting the level of, uh, sodium within that filtrate. And then that maculadenza isn't going to feed back to that just juxtalomerular apparatus, uh, to also cause a release of renin. So if we're thinking about the juxtalomerular apparatus, what we're really thinking about here is, um, blood pressure regulation both through, uh, It's gonna cause a release of renin either way, but it's sensitive to both, um, sort of distension and pressure through those mechano receptors and the juxtalomerular cells. I can't say that word. And then also um for uh sodium levels as a result of the chemoreceptors in the maculadenza. So those are sort of your, um, two things there that are gonna stimulate uh renin and just to remember. Uh, Renan, uh, is going to uh be uh responsible for detecting low blood pressure and then adjusting things accordingly. And then anti-diuretic hormone is gonna enhance the water reabsorption in the collecting duct, which is down there. And then uh it's gonna do so by activating this aquaporins in the collecting duct, allowing water to um uh leave the collecting duct so that it ends up back in the plasma. Then you have your rein angiotensin aldosterone, anti-diuretic hormone system, which I said earlier in the semester and probably freak you guys out. Um. Rightfully so. I can't remember because again we cover renal twice, but I can't remember when we covered this. So the purpose of the renin angiotensin aldosterone antidiuretic hormone system is to regulate blood pressure, fluid balance, and electrolyte levels, and then these are all your main components. So we just talked about this one, your juxglomerular apparatus, which is going to be your macula densa and jugular juxtear glomerular cells. Take a shot every time I can't say that word. I actually don't do that. Uh, and then, and the liver, that is where we're gonna have our our angiotensinogen, um, and, and then our lungs are gonna then convert, uh. Convert the angiotensin 1 to angiotensin 2, and then cause a release of aldosterone from adrenal glands. Uh, I have a good picture of that coming up. I think this might be incorrect. Um, I think I have, I have to look at it again, but I think angiotensinogen is in the blood. I don't know, I don't want to confuse you guys, so I'll just wait a minute. But, uh, the interaction with anti-diuretic hormone is it's gonna work again along arginine, uh, I'm sorry. Arginine vasopressin, vasopressin, by the way, is just anti-diuretic hormone, and but it's main job is to again maintain an adequate amount of blood volume and pressure. So, Again, this is a review, uh, of just sort of the first, uh, sort of how renin is going to be regulated. So you have those juxlomerular cells. Hey, I got it right that time. Uh, are you gonna be specialized uh mechano receptors that cause a release of renin, and that is going to be. of low blood pressure and then the chemoreceptors here are going to be uh in the maculadenza and the distal convoluted tubule, and that is going to detect sodium concentration and then feedback to the jux glomerular cells and then cause the release of renin. So this is uh the process of converting renin into angiotensin 2. renin is just sort of your like. First, uh, I guess step, but renin, so again, we're gonna have low blood pressure and uh low sodium is gonna sort of signal for the release of renin. Renin is then gonna convert angiotensinogen, which is produced by the liver into angiotensin one. Atensin one doesn't really have a lot of action, but just know that you have angiotensin one, it's gonna be converted. To angiotensin 2 by a, um, enzyme in the lungs called angiotensin converting enzyme or the ACE enzyme. Some of you guys have may, maybe have heard of like an ACE inhibitor, uh, as a way of regulating blood pressure. So essentially, if you can't convert the angiotensin 1 to angiotensin 2, then that can have, uh, effects on blood pressure. So as we see here, uh, uh, effects of angiotensin 2, we're gonna, uh, constrict our blood vessels and then we're also gonna stimulate the release of aldosterone and, uh, also trigger, uh, a thirst mechanism to be able to kind of get you to start drinking more water. This is just what I just said um in picture format. So again, you have Angiotensin uh 2. Remember, angiotensin 1 was converted to angiotensin 2 by the ACE enzyme, and then we have aldosterone secretion resulting in increased uh plasma aldosterone, and as a result, remember we have an increase in sodium reabsorption and then an increase in sodium or potassium secretion. And then the net effect is you're gonna be retaining more sodium because you have a decrease in excretion of sodium and an increase in, uh, potassium excretion, meaning you're, uh, retaining less of it. All right, Aldosterone. So Aldosterone if we remember back, is in the adrenal glands and it's going to be sort of signaled to by angiotensin 2, and its primary function is going to be to promote sodium and water reabsorption reabsorption and the distal convoluted tubule we talked about this in chapter one. Remember I said, uh, your distal convoluted tubule is sort of your fine tuning, um. Region of the nephron and the reason for that is because it's going to be heavily influenced by the actions of aldosterone. So if we have a lot of aldosterone activity, then we're going to end up wanting to reabsorb more sodium and water uh to be able to maintain the electrolyte and fluid composition and homeostatic sort of environment of the blood. Um, so yeah, again, we're going to increase the number of sodium channels and sodium potassium pumps in that distal convoluted tubule. And then we're also going to want to uh Be able to get rid of more potassium there. And the effect again, we're gonna raise blood volume and blood pressure, um, because remember, your uh solute or Solvent is going to follow your solute, so you're gonna end up retaining more water that way as well. And then your arginine vasopressin system and remember vasopressin is just anti-diuretic hormone, which I have noted here. Um, so remember that it's going to be produced by your hypothalamus, uh, remembering back to the previous exam and just remember that your uh anti-diuretic hormone, uh, is going to really work by inserting this aquaporins in the collecting duct, allowing you to retain more water. So it's gonna work sort of synergistically with the uh renin angiotensin um aldosterone system to be able to increase blood volume and uh and it's sort of doing that by increasing the amount of uh plasma slash water in your blood. And then this is just gonna be talking about activation when these systems are going to be active and not active. Um, so in, uh, instances of like low low, wow, low blood pressure, uh, you're gonna have the activation of the renin angiotensin system. So again, the kidneys are going to release renin, you're gonna have angiotensin 2 production through that, uh, sort of multi-step process we talked about, and then that's gonna really, uh, result in vasoconstriction and then aldosterone release, um. To make sure that we're squeezing the blood pressure right, so that's gonna increase blood pressure because the tube is thinner. And then we're also going to have uh uh more sodium and water, uh, allowing us to sort of maintain uh more uh fluid within the blood. So you can see how like you have a thinner tube and more contents within the tube, how that is going to increase blood pressure. And then we're also going to have the release of anti-diuretic hormone because again that is going to promote water reabsorption, which again is part of that equation. Uh, high salt intake, you're going to have anti-diuretic hormone release. So again this is to maintain the osmorality of the blood or the concentration of the blood. So if we have a lot of salt to be able to maintain the appropriate concentration uh within the blood. And to make sure that our cells all function properly and things like that, we are going to want to hold on to more water. Therefore, you're going to have more anti-diuretic hormone. Uh, yeah, that's why like if you think about eating a very salty meal or maybe you go out for Chinese food and you wake up the next day and you're like, wow, man, I look like I'm 2 or 3 pounds heavier. Well, that's not body fat, that's a result of uh water retention. And then when we're talking about exercise or physical stress, um, again, you're going to have to uh sort of alter your blood pressure. There, so you might have some uh mild activation of that renin angiotensin or anti-diuretic hormone system to kind of support you through exercise. And then in cases of inactivity, again, if we are normally hydrated and we have a stable blood pressure, there's not going to be any kind of reason for this system to sort of turn on. So as a result, you're not going to have a lot of burning production. You're not going to have and as a result from that, again, you're not going to have as much angiotensin 2 and aldosterone signaling activity, and then if you're hydrated, uh, there's not going to be really any reason to hold on to extra water. So, uh, that way that the anti-diuretic hormone, um. It's not gonna be nearly as active. So that is all of the content, uh, that was a very long video, uh, that was probably, I'm not even sure, that was like an entire movie. I can't believe I made it. Um, but yeah. I hope that this has all been very helpful. Again, I want to apologize to some extent because the past 3 weeks of school for me have been nuts, so I've really Had to um I guess reschedule a lot of these uh sort of reviews and things like that. I would much rather be doing these in person with you guys, um, but you know it is what it is, but I know that some of you rely on these reviews and uh I want to make sure that these are available to you. Um, so yeah, best of luck on the exam. Uh, it is going to be. A bit of a challenging exam for sure. Um, I don't have any review questions prepared because again you guys just have that practice test that you can take as many times as you want and I feel like that is gonna be more than adequate for you guys to be able to like test your knowledge. Um, so yeah, uh, best of luck and I will see you guys, uh, Wednesday after the exam. And it's gonna be awkward if I just stop talking, but I'm going to "