Muscles Wk 7 A&P

There is a strong relationship and we'll think about how muscle tension is generated by different factors such as frequency, such as stretching and so on. So we'll think about the way in which muscle activity and tension is regulated. We'll think about different types of contraction, isotonic versus isometric and then we'll think about the way in which muscle protects itself from damage through these two sensors that are able to protect it from either being overstretched or over contracting and then towards the end we'll think about how muscle is able to regenerate and also how it degenerates particularly with age. There is some overlap with the pathology classes and in the pathology lectures we'll be going to be thinking much more about disease whereas this is really associated with a little bit of aging at the end. So to recap from last week we talked about the fact that muscle is a voluntary muscle, so skeletal muscle is a voluntary muscle, it's able to be controlled although we discovered as we saw last week that not every single skeletal muscle is controllable but the majority of them are. They're designed predominantly to help us with our locomotion and we talked about the fact that these muscles are controlled by our upper motor neuron so our cognition is able to activate these upper motor neurons, they then send a signal down to the spinal cord, these intersect then with our motor neurons that then connect to the muscle and so the muscle can then be activated in this way so when the muscle is activated you tend to get a contraction, one muscle, one motor neuron regulates a number of muscle fibres and we talked about the size of the motor units, how small motor units give you much finer control, so for example the muscles in your eye and they tend to be much slower in activity so they have long endurance, they don't fatigue very easily and that their twitch characteristics are much slower. And then we talked about larger motor units, so you've got one upper motor neuron that's regulating a large number of muscle fibres, these are referred to as large motor units and these tend to generate a lot of force but they are mostly glycolytic in their metabolism so they rely on glycolysis and this means that they fatigue very quickly because they're not going through all the processes that help to release more ATP through the Krebs cycle and also the electron transport chain. So it's important to remember that these motor units are controlled by a single upper motor neuron which consists of a cell body which is embedded within the spinal cord and then you've got a long axon that then connects it to your muscle fibres and then they're innervated by these axon terminals and this is what determines the sort of communication between the nerve and muscle and last week we talked about neuromuscular junction and how neuromuscular junction plays a role in controlling the contraction of skeletal muscle. So the upper motor neuron is the size of the upper motor neuron depends on the number of muscle fibres that it innervates so you can see that when you've got an upper motor neuron here you've got the cell body which is embedded within the spinal cord but then you've got these axon terminals and so the higher the number of muscle fibres it's got to innervate then the larger the axon needs to be in order to be able to innovate these large number of muscle fibres. So generally speaking the larger the number of muscle fibres that an upper motor neuron is innervating the larger than the upper motor neuron is going to be and so is the cross-sectional area and so large motor units have large upper motor neurons and small muscle units have small upper motor neurons.

We talked last week about contraction of muscle that it involves the interaction between the thin filament we talked about this in great detail how the thin filament is made up of two polymerized chains of actin molecules that start off as globular actin and these polymerize into filamentous actin and you know how these are put together we talked about the fact that you've got this very important protein you've got these complexes that are associated so you've got topomycin and you've also got the troponin complex so troponin complex has three troponins troponin I T and C and the C binds calcium and so in the presence of calcium we can get contraction if there's ATP present so some of you will have been have done the practical looking at actin myosin and so hopefully you now understand that ATP is needed for contraction but it's also needed for the thin filaments to separate so in the absence of ATP this is why you get rigor mortis because the the two filaments interact with one another when you need ATP to break that so initially what's going to happen ATP is going to bind and there's going to be a changing conformation that now separates the thick and thin filament eventually what happens is that there are a series of different stages in which the ATP is first hydrolyzed but the ATP and the ADP are still attached and they come off in different stages and so initially the phosphate group comes off first and then the ADP comes off and this is associated with the power stroke and enables the thin and thick filament to interact together but generally speaking what happens is that the thin filament moves towards the center of the sarcomere so if you remember the sarcomere is the smallest unit of contraction you've got your thin filaments and your thick filaments and during a power stroke the thin filaments so we're now going to think about there's a few definitions that you need to remember so tension versus load so the tension muscle tension is the force that's been generated by from within the muscles so the muscles are contracting obviously those thick and thin filaments are interacting together and when they interact together that generates the force so the tension the muscle tension is the force that's been generated by the muscle the load is the force that's been exerted on the muscle through any mass that it's moving so if you've got a load that the muscle is trying to pick up then the load is the weight of that load is referred to as the load or the force that is exerted on the muscle and that's usually the means through which the muscle is going to do work by moving that object so the tension that's developed within muscle depends on three main factors frequency of stimulation so how often it's stimulated we talked about this a little bit last week where we said that if it was stimulated too frequently then it would fatigue but this is talking about much shorter levels of stimulation strength of stimulation as well and then finally the degree of muscle stretch so in the 1700s there was a physician physiologist who was called Luigi Galgani and he started to experiment with electricity and muscle so he used frog's legs actually and he connected these to a source of electrical activity and he was one of the first to notice that you could twitch muscle even from a dead animal by stimulating it with an electric current and one of the things that he noticed is that there was a threshold a certain threshold was needed so you needed to so even if you stimulate the muscle you needed to reach a certain voltage in order to actually get a response from the muscle and that's referred to as a twitch so this is a twitch here so during the twitch you get a an increase in tension which reaches a peak and then and then it if you leave it it will start to relax and so this is the relaxation period so he noticed that you could generate this artificially by stimulating the muscle but of course there was this threshold over which you needed to get to in order to be able to stimulate the muscle and his work and subsequent work showed that you could cause a muscle to twitch by stimulating it and that there were three main sections to the twitch there's a latent period which is about five milliseconds and this is the time that it takes for the electrical activity to pass into the muscle and to depolarize the membrane on top of that you've then got to release calcium from the sarcoplasmic reticulum then you've got you've got to get them to bind the thin filament and then to generate the contraction of the muscle so all of that together takes about five milliseconds so it takes a few milliseconds for that to happen so even if you stimulate the muscle before it responds there's going to be this latent period for all of those different factors that I've mentioned to happen first before you're going to get contraction and then we're going to develop increased contraction up to a peak and then we're going to then get a period of relaxation so the period of relaxation this period here is going to be affected by the rate at which calcium was removed from the cytoplasmic space so this is going to be affected predominantly by the off rate of remember the calcium is bound to the myofilaments so they've got to come off and then they've got to be they've got to be taken up by the cytoplasmic reticulum the calcium ATPase protein back into the cytoplasmic reticulum so all of that takes time and the calcium concentration decreases as the relaxation period continues and different muscles have different twitch characteristics so fast muscles generally speaking tend to have tend to have faster twitch characteristics so they they contract more more quickly up to a peak and they relax more quickly as well and these are these are two muscles within the the leg gastrocnemius and soleus and both of these are slightly slower than those found in the in the eye and you can see that it takes much longer to reach peak contraction followed by a longer period of relaxation so each muscle is going to each muscle fiber is going to have characteristics which are determined by some of the things that we talked about last week you know so for example the myosinative PAs is going to have a different enzymatic activity the calcium ATPase and some of these different characteristics you know in terms of the way that they generate energy all of these factors will determine how fast the muscle is and how slow that was and we covered that towards the end of last week so if we contract a muscle and we trick cross muscle the tricks so these these small triangles here represent the points at which the muscle is stimulated if we stimulate the muscle then we're going to get a twitch and then if there's sufficient amount of time between each twitch then the muscle should fully relax and each time that we twitch this muscle we should get an amplitude that is about the same as before however if we don't allow the muscle to fully relax because you can see that this takes some time here to relax if the muscle doesn't fully relax and we stimulate again then what happens is that we get a second contraction which is higher and bigger than the first and this is the process this is what's called summation so the the the size of the twitch increases or the size of the tension the degree to which the muscle contracts is much higher the second time than the first time and that's because not all the calcium in the cytoplasmic space has been taken up remember it takes time for the cytoplasmic we stimulated the muscle before it's all been taken up so now we've got more calcium here than we did here and there's more calcium to bind the myfilaments and therefore you get a much stronger contraction and this is referred to as summation because you're essentially adding to what you have before so you can repeat this process and if you keep twitching the muscle up to a point you're going to keep getting increased tension until you'll get to a point where you get this here where it's it's an incomplete tetanus because you haven't got a plateau phase you've got slight dips in between but essentially this keeps increasing because you've got more and more calcium that's within the cytoplasmic space and so you're giving the muscle only a little time to relax if you stimulate this sufficiently fast then you will get a complete tetanus of that complete contraction where the muscle doesn't relax in between periods of stimulation at all however even if you keep going eventually what will happen is despite the continued stimulation you do get to decrease in tension and that's because of a number of reasons first of all the muscle becomes fatigued because you're using up ATP for example gets used up also because the muscle has been made to work so fast and hard you get a lot of anaerobic respiration through glycolysis and this of course produces lactic acid and so the pH drops and the lower pH interferes with the contractile apparatus and therefore you start to get a decrease but also finally you also get an imbalance of iron concentrations remember in order to stimulate the muscle sodium needs to come in but ideally we need to be able to activate the sodium potassium exchanger to pump that sodium out in order to allow the muscle to relax fully and then we stimulate it so if you keep that stimulus on then of course there isn't enough time for the sodium potassium exchanger to remove the sodium ions so eventually you don't have enough either you get an imbalance of of ions either side of the cell membrane and that obviously is going to affect the tension generated as well so also you can get an increase so eventually what should happen is that you've got this threshold here and when we're below the threshold we don't get any stimulus stimulation at all and eventually what happens is that when we start to stimulate the cell and the muscle over and about the threshold period we continue initially to get contraction and as we increase the voltage we get more and more stimulation so the tension increases up to a point and the question is you know why does that happen well that's because in a muscle you've got different groups of muscle fibers which are of different sizes and these have different activation thresholds so the smaller ones are going to be activated first and then as you increase the voltage the larger ones start to get activated so this is really good because it allows a muscle a muscle to be able to generate different amounts of force so when you stimulate that muscle it's it's not going to generate its maximum force you can fine tune the degree to which that muscle stretches because by altering the degree of stimulation you can get that fine tuning and that's because different motor units have been activated so again back to our regional diagram so here we're below the threshold and then as we increase the voltage we start to get twitches which are increasingly larger as we increase the voltage and the reason for that is because at the lower voltages the smaller motor units get activated first and then as we increase our voltage then we start to bring in alpha motor units which are much larger and then eventually we we bring in the one the largest ones and so all of these contracting together and generate tension that produces a large stimulus so this enables the muscle to be to generate different levels of tension so if we want a lower level of tension then of course we can stimulate it more at a lower level and again this is also called summation because and recruitment because we're recruiting more and more muscle fibers that are going to contract and generate that tension so the reason why that happens is because smaller muscle units are activated first and larger muscle units are activated later on so at lower voltages you don't get as much activation so those of you who did physics will remember Ohm's law which tells us that voltage is equal to the product of current times resistance so in these small motor units we've got a small axon and the cross-sectional area of the axon is smaller therefore there is more resistance so you need a high voltage in order to be able to to activate them okay so it's all to do with the degree of resistance in these in these in these small versus large fibers and when you have large fibers of course the resistance is very low so you need a much higher voltage in order to activate them and you've also got lots and lots of iron channels on there so so when we're trying to stimulate the muscle then the smaller muscle units as muscle fibers are going to be activated first because they have these small alpha motor neurons which are triggered first and then as we get larger voltages we are able to then activate the the larger muscle units and that generates of course more force so next we're going to think about another way in which skeletal muscle regulates the degree of contraction now unlike smooth muscle and cardiac muscle of course most muscles skeletal muscles are associated with bones and that helps to maintain the length of of the muscle however there is a optimal level of contraction so if you remember this this is the sarcomere so we're going from z line to z line or z disk to z disk and we've got our smallest unit of contraction here so if you remember in some of the previous lectures we'd mention about the sarcomere being around two microns in in length so hopefully you've got a sense of what that means because you've been looking in particularly in pathology under the microscope and using your ip strategy to look at distance so this is about two microns here and we go from about so the sarcomere ranges from about 1.8 to about 2.2 and there is an optimal level of contraction here that is appropriate so if there is too much overlap between the thick and the thin filament then there aren't enough cross bridges that are formed and therefore you don't get as much force as you start to move the thin filaments apart you get more and more cross bridges formed remember the force that's generated depends on the interaction between each of the thin and the thick filaments the the actin and the myosin heads so when they interact together then they they generate the mechanical activity so as we shorten the the as we lengthen these cross bridges forming and so more tension is generated and then eventually we reach a point which we've got the most number of cross bridges have informed between the actin and the myosin and then if we start to then continue to stretch the muscle so that there's now less and less overlap between the thick and the thin filament we generate less force because there are fewer cross bridges formed and so muscle tries to ensure that it it works at the optimal length and obviously if you do this then you're going to also damage the muscle and last week we talked about titan which is a spring that connects the thin it connects the the thick filament here to the z line and so as the muscle pours apart the passive tension that's generated by by acting so by by titan increases and it stops the muscle from overstretching so that's one of the factors tension is also can be affected by a number of factors so we've talked about stimulation frequency we've talked about strength of stimulation and so all of these factors determine how much the muscle generates force but even if you were to maintain the same stimulus the muscle will continue to generate a bit more tension and that's because as we work the muscle not all of the calcium is going to be taken up so you're going to get some increases in intracellular calcium which is going to bind more myfilaments and cause a higher tension to be generated but also the muscle as it's worked starts to heat up now some of you may know about the q10 law that tells us that enzymatic activity or metabolic activity tends to double for every 10 degrees celsius increase in temperature so metabolic activity increases as a result of increases in to warm up first because that helps to increase the activity of the muscle but also stretching helps to also increase the because the the muscle has got intrinsic stiffness it's important that when you warm up this reduces the amount of stiffness against which you've got to work so all these factors play an important role so if you're going to the gym and wondering why it's important to warm up before before you exercise well you protect the muscle as well you're less likely to damage it if you if you warm up the muscle because the the stiffness decreases and therefore the you have to do less work to overcome that in order to generate your mechanical activity so there are different types of muscle stretch so we can have so-called isotonic and isometric contractions so as shown here iso means the same and tension is ton means tension and metric means length so if we want to have isotonic then we're going to have the same tension isometric is where we're contracting the muscle so we're generating tension and force but the muscle isn't actually shortening so these are the two two main ways which muscle can contract so we've got an example here so you can see that we generate tension up to a peak so we've now got peak tension which isn't changing but despite the facts that we've got the same degree of tension you can see that the muscle is shortening so we're going from a hundred percent length and it's now shortening and so this is what's referred to isotonic so it's the same tension but the muscle is lengthening in this case what we've got here is that we've got the muscle length has stayed the same so it's you can see it's remained the same throughout the whole process but we're actually increasing the tension so the tension is increasing but there was no change in muscle length and even we now relax the muscle and the muscle length has still stayed the same so this is referred to as isometric because the length remains the same despite the fact that the muscle is generating tension so why does this happen? Well it's all to do with the myofilaments and the connective tissue that's either side of the muscle fibers so when we have an isometric contraction so we've got our muscle here and so when the muscle contracts normally you would expect this lever to to be lifted upwards but when we have an isometric contraction we're generating tension within the muscle here but we're not actually shortening the muscle and the reason for that is that the sarcomeres that are shortened during contraction are actually getting shorter but because you've also got connective tissue in series with these sarcomeres the connective tissue lengthen whilst these muscles shorten so actually to the observer there is no change in muscle length but actually the muscle is lengthening but actually what's lengthening is the connective tissue so the tendons on either side are lengthening and the muscle is actually shortening so it is overlapping with one another and it's generating tension but the muscle to the eye isn't shortening.

So next we're going to think about ways in which muscle protects itself from damage so muscle is very easily damaged either from over contraction or over stretching and so the muscle has different ways of protecting itself remember that we also want to make sure that we maintain that sarcomere length that there's an optimal sarcomere length that produces the most amount of force so all these factors mean that you don't want to either over contract the muscle and have too much overlap between the thick and thin filament but you also want to make sure you don't over stretch the muscle so that the interaction between the thick and thin filament are sufficiently not overlapping.

are sufficiently not overlapping. So there are two systems that help to protect the muscle from damage so we've got two systems here one which controls the muscle stretch so this is the gaudy tendon apparatus is the one that is involved with over contraction of the muscle and we'll talk about this in subsequent slides so the gaudy tendon apparatus is associated very very close to the connective tissue the tendons that are at the end so they are able to detect the degree of over contractions when the muscle is over stretched then this is going to affect maybe it be activated is going to activate the muscle spindles so the muscle spindles are found within the muscle itself so if we first of all start off by looking at the muscle spindles so periodically throughout the muscle there are these areas within the muscle that don't have my filaments so these have got specialized fibers and these fibers are able to to sense the degree of stretch so when the muscle is it's been pulled apart and the sarcomere start to lengthen obviously the muscles either side of the muscle spindle are going to lengthen and that's going to activate the sensors that are within the number of different motor neurons so you've got some you've got motor neurons that connect to the central nervous system which are going to actually be activated by the fact that the muscle spindle has been activated and then you've also got gamma out motor neurons that are also connected to the central nervous system so these gamma motor neurons when they activate cause the so the idea is that when the muscle is being stretched then that's going to trigger the activity within the muscle spindle that's going to send a message to the spinal cord and that's going to activate these gamma motor neurons which then contract and oppose the stretch that's that's happening so the idea then is that you're stopping that muscle from you're resisting the stretch on the muscle so this is very important so there are these small regions here that are devoid of sarcomeres so they don't have the typical muscle sarcomeres that you find but these specialized sensors that are able to detect stretch and actually these muscle spindle fibers are important not just for protecting the muscle from being overly stretched and damaged but they also help to maintain tension within the muscle so when the muscle is not completely active in terms of moving an object there is still tension within that muscle and that's generated by these fibers so so when you have these muscle fibers here what happens is that they're activated so there's a low level of activation even when the muscle is not being stretched and these activate these sensory neurons and they interface with alpha motor neurons in the spinal cord and this generates a low level of contractility within the muscle so there is some tension they're not enough to contract the whole muscle but enough to generate some some tension so that there is there is some tension generated within the muscle and this is why muscle is highly energy consuming because even at rest because you've got this tension that's been generated it's still using up lots of ATP even if you're not contracting the muscle and that's why when you're not using the muscle it gets it gets degraded relatively quickly and you get muscle atrophy when it's not being used because even at rest it helps to use up a lot of ATP and increase your metabolic rate so you're not getting full tetanus here at rest because you are not contracting the muscle fully but you're generating enough tension through these sensory neurons that are being that are activating the alpha motor neurons at a lower level so you can see here that the way that it works is that if we've got at before we stimulate stimulate stimulate the muscle or through stretch there is always some level of activity through these so these sensory neurons within the muscle spindle are always going to be sending out signals but at low level so there's going to be some tension here but there's going to be some some tension here but if we start to stretch the muscle if we pull the muscle and we stretch it then what's going to happen is this is going to increase the activity within the sensory neurons it's going to send more signals to the spinal cord and this activity is going to increase the activity in the gamma motor neurons that are associated with the ends of the muscle spindle and that's and that's going to cause that's going to resist the stretching of the muscle and resist it so that the muscle doesn't stretch any further and that activity will will stay high as long as the muscle is stretched and then as soon as the the muscle returns to its normal length then you go back to the kind of basal level of activity within the muscle spindle okay so sometimes when you go and see the GP they might they might get out their little hammer and check for peripheral peripheral neuronal damage and this is called westfall sign so this is where you you'll the doctor will hit the patella and what happens is that the the striking of the patella lengthens this this quadricep muscle here and when when the quadricep muscle is stretched as a result of the striking of the patella then the kneecap then what's going to happen is that this lengthening of the muscle activates the muscle spindle and then you what happens is that you act you it sends a signal to the spinal cord the spinal cord is then innovated and connected to gamma motor neurons that then activate and contract the muscle so if you haven't got any peripheral nerve damage then as soon as the patella is hit you should get a forward movement of the leg and this is called the westfall sign it's used for checking for peripheral nerve damage as i said this actually is completely involuntary so it doesn't require any of the upper motor neurons at all so you would know that it was happening but you can't control this so it's beyond the control of your cognition and the upper motor neurons this has just happened peripherally between the muscle and the spinal cord so this is looking at peripheral nerves peripheral sensory nerves so next we're going to think about the golgi tendon apparatus so the muscle spindle found in here and within the muscle fibers themselves are important for detecting stretch now we're going to think about the golgi tendon apparatus which is activated by over contraction of the muscle so again you you have a similar system here when the muscle over contracts then obviously tension is generated in the golgi tendon and again these also have sensory neurons that send signals out to the spinal cord so together both the golgi tendon apparatus and the muscle spindle work together to stop the muscle from being either over contracted or overstretched so that we can maintain that optimal sarcomere length for contraction to generate the right amount of force and also of course to prevent the muscle from being over contracted and damaged as a result muscle is very sensitive to being damaged through overwork and you can see how actually this works in in practice so how both the golgi tendon and the muscle spindle work together to protect both muscles so here we have our tricep muscle and our bicep muscle and of course these are antagonistic muscles so they work against one another but in order to ensure that neither is either over contracted or overstretched these two systems work in practice so if we over contract if we over flex our bicep muscle here and so this is going to be short this is going to shorten and this is going to lengthen isn't it so the idea so well if we over contract our bicep here what that does is it activates the muscle golgi tendon apparatus or golgi tendon organ here so this is going to send it's going to activate these nerves these afferent nerves and connect to other nerves in the spinal cord so activation comes from the fact that this muscle has been overly contracted and shortens too much so what what that has has two effects what it does is it decreases the activity of the alpha motor neurons that are in the muscle that's been overly contracted so it's it's going to so obviously in order for muscle to contract you have to activate the alpha motor neurons as you know but actually what this does is that when it's been over contracted that this this nerve signals to the alpha motor neurons and decreases their activity so it's so within it's the muscle itself is actually forcing the muscle to contract less on the other hand interestingly that same nerve also intersects the antagonistic muscle the extensor muscle so also going to affect the activity within the tricep muscle behind it so here the activity is going to increase in the alpha motor neurons in the extensor muscle and so this causes this muscle to contract so when you when you try and over flex what happens is that the electrical activity within the alpha motor neurons decreases to stop you from over over contracting that muscle but then you get increased activity in the antagonistic muscle so that causes the antagonistic muscle the tricep muscle to contract and oppose this muscle to protect this from from being overly shortened because if you think about it when you over flex this muscle this muscle can get damaged from being over flexed but on the other hand the antagonistic muscle can be damaged from being overstretched so the two muscles are working together to ensure that they protect one another and that you don't get sufficient damage I think what we'll do is we'll have a quick break and then I'll come back and then we'll start on the second part which is about how muscle generates regenerates and degenerates okay so we'll have a quick break maybe we'll maybe we'll continue it about between between five and between five two and five o'clock so in the second half we're going to be thinking about the way in which muscle is able to regenerate and to grow in response to different stimuli and then we're also going to think about the way in which muscle is able to regenerate as well particularly in response to aging so what are the stimuli for hypertrophy?

so what are the stimuli for hypertrophy? I hypertrophy when muscle gets bigger and muscle gets bigger through growth and that means that it needs the building blocks of building blocks of growth which is going to include proteins and increased energy it's going to need a stimulus in order to help it grow so these are usually hormones of various types that allow the muscle to be able to grow and then finally we need a stimulus and this can be mostly in the form of mechanical activity so the muscle has to be worked so it's often sometimes if you look on the internet sometimes they they talk about ways in which you can get your muscle to grow in your sleep by doing nothing essentially muscle needs a stimulus in order to to grow so we haven't yet found a sort of magic way of doing no work and growing the muscle.

There are three types of muscle fibers I hope you remember this in last week you've got type you've got type one and then you've got type two but type two is broken into two sections type 2a and type 2b so type 2a has got characteristics of both type one and type 2b and they can type 2b type 2a can become more like type one so slower muscle so type one is a slow muscle and type two is a faster muscle but type 2a is has some of the characteristics of slow muscle type one or faster muscle type 2b and it's the most trainable so depending on the type of work that that muscle does it can either become more like a slow muscle type one muscle or it can become slightly faster more like a type 2b so these muscle fibers are able to hypertrophy so they increase in size now the slow muscle the fast muscles these are the these fast muscles the ones that can grow the largest because these are the ones that produce a lot of force but they are also easily fatigued and hypertrophy is more prominent in type 2b fibers because these are the ones which are the largest they've got the largest cross-sectional area they've got the smallest amount of glycogen in them and they're much more on glucose and also on glycolysis rather than oxidative and phosphorylation and so there is also a great deal of variation as I'm sure you know that there are some people that don't have to do much exercise and you know they can grow their muscles very very rapidly and extensively where other people will have gone to the gym for years and you know hardly have anything to show for it and a lot of that is is genetic as well in terms of the way that we respond so hypertrophy is an increase in size it's a bit similar to what happens to the heart these muscles get larger although there are big differences so in the heart the muscle fibers or the muscle cells the myocytes are separated so you've got separate muscle cells what happens with skeletal muscle is that you get myoblasts these are the muscle cells and eventually what happens is that when the muscle is maturing you get fusion of the cytoplasm of these different myoblasts so you get one large muscle fiber that then consists of lots of different nuclei from what was originally separate cells so the hypertrophy is very different it can be caused by fusion of new myoblasts into muscle fiber to make that fiber bigger so it will have multi nuclei so there'll be lots of different nuclei in and around that muscle so the so that can help them either the cross section to grow so hypertrophy is when the muscle gets bigger and that can happen as a result of an increase in the cross section of the muscle or it can result in an increase in the length of the muscle so all both of which are considered hypertrophy now with cross sectional area that happens by the addition of sarcomeres in parallel and with an increased muscle length they're added in series so the muscle gets longer so most of the time muscle gets bigger through hypertrophy and so this is explained here so we've got our original muscle fibers this is a cross section through the muscle and if we are going to hypertrophy the cells then we don't increase the number of muscle fibers we have but we just enlarge them so they get bigger and this is usually through fusion of additional myoblasts that fuse with the cells that are the muscle fibers get larger when we have hyperplasia then what we're doing here is that the muscle fibers stay the same size but we produce more often so you get cell division that produces more muscle fibers and so this is referred to as hyperplasia and it involves cell division so essentially what happens here is that when the muscle lengthens then we're going to add more sarcomeres in series we're going to add them at the ends and the muscle gets longer if we are going to increase the cross-sectional area of the muscle here and make the muscle thicker then we're going to add them in parallel so they're going to be added in blocks and essentially on top of each other and that makes the the cross-sectional area thicker a thicker muscle also generates more force because if you think about it if you've got um if you have more of these muscle fibers in series the muscle gets longer but its ability to generate force doesn't really increase however if you put them in parallel with one another so if you stack these on top of each other then you've got more cross bridges on the vertical plane and that means that when the cross bridges are form and muscle contracts it generates more force so you're trying to get if you're gymming and you're trying to get be able to lift more weights then you can lift more weights by having a muscle that has got a bigger cross section because it can generate more force through a greater number of cross bridges being formed and some animals are thought to be able to increase their muscle fibers through hyperplasia in cats but this is not thought to be a mechanism in humans so in addition to making the muscle bigger through hypertrophy the muscle fibers also have periodically if you were to to look at the the muscle fiber you would find that there are satellite cells which are located periodically along that muscle fiber and these are usually very quiescent so they're cells which are if you like resident stem cells which sit on the muscle fiber and they're pretty quiescent they don't do very much but once the muscle is damaged one is trauma to the muscle the sarcolemma is broken then they have chemosensors that can detect the products of damage from the muscle and as soon as that happens they migrate to the site of damage and they are able to proliferate and fuse with the muscle so this enables them to facilitate repair to that muscle fiber so if you're exercising and you injure the muscle and if you lift more than you were used to then you're going to start to get muscle pain and that's usually associated with damage to the muscle and that will activate these satellite cells they'll move to the site of damage and they'll proliferate and fuse with the muscle and eventually when that hyperplasia of the satellite cells the resident stem cells are going to divide but they're more fused with the muscle so when the muscle gets when the muscle grows and gets too big then sometimes those fibers will split into smaller units because the diffusion distance is going to increase obviously we want to be able to get oxygen and nutrients in there more readily and of course once the muscle fiber gets too large it becomes much more difficult for diffusion to facilitate the delivery of oxygen and nutrients and therefore the the cells the muscle fibers can split and that helps to facilitate so this is not referred to as hyperplasia it's still muscle growth but it's the way in which you end up with more muscle fibers but these are from splitting of original the original muscle fiber and you don't get more nuclei you just get the same number of nuclei in a smaller muscle fiber so you you can also facilitate a muscle growth through stimulus and various stimulus so taking in certain nutrients can activate muscle growth IGF is a circulating hormone that is an insulin growth factor that can also facilitate muscle growth and of course mechanical activity so you can either do it through the best way to get the most efficient growth is to combine these three together but each of these in and of themselves can generate some limited amount of growth but if you combine these together they all converge on a similar pathway so they activate and calcium urine is a calcium sensing protein and downstream you get a number of different signaling molecules that are activated and this what this does is it increases transcription of the components that you need to build bigger muscles so generally speaking they tend to activate protein synthesis so these are liposomes here and these are essex as a ribosomal unit subunit and these are activated to produce more protein so you get more transcription of RNA and also translation of the RNA to protein so you're getting more building blocks that the cell is going to use to build bigger fibers so these three components are very important and now one of the factors that can activate muscle growth steroids and they have been shown over the years to significantly increase muscle growth so here is a paper that was published some years ago but what they did is they took a group of men they divided them into two one group they gave well they gave both groups testosterone so they gave them a super physiological dose that's higher than what you would normally get in your body in terms of concentration so they gave them this amount and divided them into two for a period of 10 weeks so they both had the same amount but one group had weight training in combination with the testosterone and what they found after a period of 10 weeks is that both of them both groups whether they exercised or not increased their lean body mass so the the smallest increase in body mass came from those that were untrained but they still put on an average of six pounds which is quite a lot of lean body mass but for those that combined it with training they got more than twice the amount so you can see that if you have a stimulus along with steroids and growth factors and exercise then you can significantly increase the growth of the muscle however it isn't generally as you know recommended in fact there've been several athletes who have died prematurely actually have sudden cardiac death because of the impacts that steroids can have on the heart but that's another subject all together but so if you take steroids than this so in this particular study when they did it because it was a very short study they didn't see any negative impacts but it's well known that if you use steroids for long periods of time then you increase both where you increase LDL so this is the two main forms of cholesterol so this is supposed to be the bad cholesterol and you get a decrease in the one that tends to protect you so the steroid hormones you can see that they have a very similar structure they're all derived from cholesterol so cholesterol is the starting product for you can see that a lot of them can this is cortisol which is a stress hormone but you can see that progesterone and estradiol these are a female and male hormones so by taking in adding exogenous cholesterol so by adding exogenous testosterone what this can do is normally what happens is that the cholesterol should be the source through which the male testosterone and another products are produced but if you start to take exogenous testosterone what can happen is that this can drive the reaction in the backwards direction and you end up with more cholesterol and that's why you can get high levels of LDL so this has negative impacts later on because obviously the body wants to keep everything in balance and so if you take in too much then we remove it by sending this in the backward direction so this is why you can have negative impacts from taking too many of these anabolic steroids so testosterone is a classic muscle builder it's produced more predominantly in males than females about 95 percent of it is produced by the testes and the other five percent by the adrenal glands that sits just above the the kidneys it has strong androgenic and anabolic effects so you can build muscle if you activate the the signaling pathways associated with testosterone they were they were sort of first used extensively after world war two particularly in prisoner of prisoner of war individuals that had lost a lot of weight and muscle and this was this was used to help them recover and to regain muscle mass especially those that have been rescued from concentration camps so it's been shown to to to increase muscle mass when it's when it's administered so because of its because of the benefits that it has to muscle growth obviously anabolic steroids have been have been banned for for years through different athletic bodies you know these are and there's lots of screening for it so that athletes can avoid it but there seems to be a sort of cat and mouse game here because you know there are people that are synthesizing new products that mimic these anabolic steroids that are well known and so the the testers are usually a little bit behind those that are producing the drugs because of increase your ability to to exercise and also to produce better performance if you if you take them so if we go back not to exogenous stimuli but actually ones that are produced within the body itself then if we look at testosterone its levels go up just just before the pre-properescent years in males and this continues to increase from it to a peak of around at around 15 years of age and it stays high until your early 30s and then it starts to then decrease and many of the changes in muscle mass are associated as we age are associated with the loss of testosterone and as I mentioned before IGF which is a growth growth hormone this decreases again from your teenage years so for those of you that are wanting to build muscle these are the optimal years you know from about 15 to about 25 this is where you have the highest levels of testosterone and of growth hormone as well in combination that will give you the best muscle building potential so those of you that want to build your muscle get into the gym now because you're just the right age for that but then you know after the age of about 30 that starts to drop and and as we age because of the loss of muscle mass which is often referred to as sarcopenia there is also loss of performance now in sport the rate at which muscle is lost is going to depend on the individual and its impact on the performance is also going to change depending on the sports that's been done so here are three different sports that have been compared so we're comparing the loss of performance from the peak period which of course occurs somewhere between 20 and 30 in most physical sports and you can see that the rate of decline does differ considerably depending on type of sport that you're doing and that's because it depends on the muscle groups that the sport depends on so if you're playing basketball then the loss is much happens much sooner and much more rapidly than some of the other approaches and for example when it comes to running even quite people that are a little bit older can still run at quite a fast pace and the reason why for those for those playing basketball are affected so this particular muscle here this is the extensor digitorium which is in the in the foot loses its it starts to to degenerate as you get older and actually this is these are these are biopsies that have been taken from different individuals this is where you can insert a little needle that takes a bit of the muscle and you can analyze this and what they've done is they've looked at the different number of motor units now the higher the number of motor units you have the more control you have over your muscle if you remember the smaller the motor units the more control you have so you can see that with age there's a decline in the number of motor units but i think what's interesting here is that even at whatever age that you look at you can see the degree of heterogeneity that there is there is a big difference even within individuals at the same age and that really depends on how much exercise and training they're doing and also genetic factors so if you're starting off here then you're less likely to to lose muscle as rapidly than if you're already down here you can see that there are people that are over 60 that have got the same level of motor units as people in their 20s depending on how much exercise and how how fit they are but generally speaking at with age you're going to get this decline in the number of motor units which is associated with fiber atrophy so the fiber the muscle fibers are getting smaller and if you exercise then you can maintain that muscle mass for much longer so if you keep that stimulus on then you are going to reduce the amount of muscle loss that happens so generally speaking there are two factors that happen with age so there is a loss of muscle size so the the muscle fiber gets smaller so the cross-sectional area of the muscle gets smaller and you also lose muscle fibers and what research has shown is that the loss of muscle the atrophy that takes place the the shrinking of the muscle fiber can be somewhat reversed or prevented or slowed down by exercise but loss of fiber is much more difficult to to replace so if we if we look here so this is looking at the effect of aging so if you've got a muscle you're going to have lots of different muscle units you're going to have different motor motor units some of them are going to be small some of them are going to be medium some of them are going to be large but what seems to happen with age is that there's reinnovation of these so that first of all there's a loss of motor neurons so you lose some of them because neurons tend not to divide as well so as we as we age and we lose those motor neurons they're not replaced and so the ones that are there reinnovate into the ones which are already there so eventually you get fewer motor units and those motor units are larger so you have less control so if you're thinking about a sport which requires more finesse and more control then you're not going to have as much capacity to be able to to do that sport you know to the these motor units and you're getting larger motor units that can produce more force but you don't have as much control and finesse over them so the muscle units get larger and yet fewer of them so as we age what happens is that you're more likely to to get an injury when you exercise you're more likely to pull a muscle and what then happens it's been shown experimentally that those muscles take longer to heal after they've been injured and you're more likely to get more severe muscle damage which is irreversible as you as you get older so more likely to get damaged and the rate of repair is also slower so if you think about those satellite cells that migrate to the site of injury and and proliferate first of all their ability to sense the the chemo sensing ability decreases with age so they're less likely to sense damage they migrate more slowly to the site of damage and their ability to divide is also impaired as well with age so that means that the ability of those satellite cells to repair the muscle or decrease with age so as we as we age there is so this is general muscle mass as a percentage of what you have at the age of 20 so around 20 is where where you have for most people have the highest amount of muscle percentage and muscle and as we age we gradually lose that muscle mass and again you can see huge amount of variation between individuals so that you can see that even at the age of 85 there are some people that have got more muscle mass than people in their 30s so again it depends on how much exercise you do so as we age we're going to initially especially when we're young we're going to produce lots of muscle and it's going to reach its peak around 25 or so and after that there is a slow decline but the rate at which the decline takes place is going to depend on how much exercise we do so we can maintain this first of all we can produce you can move the muscle mass to a higher starting point before before degradation and atrophy so if you exercise you're going to have more muscle to begin with and it's going to decline more slowly and this is important because as individuals get older there is a threshold below which you start to be physically affected by that loss of muscle mass and this is associated with disability particularly in older individuals and this can cause them to to fall when they when they try to stand up and so on so the more you you exercise the more you're still going to lose it but the rate at which you lose it is going to be significantly slowed and down and this has implications really because if you think about the fact that there is an increasing amount of obesity in other words that you know people were all putting on more weight because of our sedentary lifestyle as we get older our basal metabolic rate decreases so you can see here this is our highest metabolic activities is highest when we're really young and then as we get older our metabolic activity slowly decreases and that's associated significantly by the amount of muscle mass that we have so the decline in latter years occurs as a result predominantly of the loss of muscle members we said that even at rest the muscle maintains tension so that uses a lot of ATP and interestingly if we from about the age of 25 our basal metabolic rate declines by about two percent every 10 years so you can imagine that someone who is 45 is going to be about four percent metabolic rate is going to be roughly about four percent lower than it was at the age of 25 now that may not sound very much but if we do a little bit of maths here if we take the average calorific intake for a man has been just over 2 000 calories and for women about 2 000 calories then two percent represents about 50 calories in a man and about 40 in a woman we can also work out how many calories are in a pound of adipose tissue or fat so if we look at a pound of fat roughly half a kilo of fat is equivalent to about 3500 calories so you can do the calculations and work out that a two percent decline in metabolic rate is equivalent to about four pounds of fat so you have got to either increase your physical activity or yeah you see you've got to find a way to increase your metabolic rate or eat less in order to not put on that weight so if you maintain the same diet same physical activity as you get older of course it's going to be more excess because you are start going to start putting on weight and so two percent declines equivalent to about four pounds of fat a year and that's going to be over four pounds sorry yeah it's going to be it's going to be over over over four pounds over four years over stone in four years so stone is 14 pounds so you're going to see you've got more than a stone in about four years and that's why as we get older and more sedentary we tend to do less exercise this is not good for our health and we're more likely to then develop all these other diseases that are associated with obesity so muscle plays a really important role in maintaining our metabolic rate and protecting us from diseases such as diabetes of course because muscle plays a really important role in taking up both triglycerides and glucose from the bloodstream and ensuring that we maintain good glucose uptake so glucose resistance to glucose will become an insensitivity to glucose or diabetes tends to develop when we lose muscle mass as well so there is a very important aspect here so if we increase our lean body mass remember I said that muscle is very highly metabolic and so it helps you consume lots of energy if we can increase our lean body mass by 10 pounds then this will lead to an increase of 70 to 80 calories a day being consumed and you can see that when you've lost 40 40 or 50 is equivalent to about four pounds of fat a year so you can see that by increasing your muscle mass this is just going to be helping increase your metabolic rate and reduce obesity and actually what's been shown is that obesity increases the rate of muscle loss so again we don't fully understand the mechanism by which this happens so as we age we undergo sarcopenia so if we look at the muscle we can see that the muscle fibers get smaller so this is a cross-section through muscle we get fewer muscle fibers and we have smaller muscle fibers and this is associated with a loss of strength and so older people tend to have become more frail interestingly what's been shown recently is that if you're overweight or obese then the loss of muscle mass associated with aging happens more rapidly which is of course problematic and so and of course that's going to be that's going to result in I think it's gone to bed so that's going to be associated with lots of potential diseases you know such as heart disease and other risk factors such as increases in lipids circulating lipids and diabetes and so on and of course it's going to increase the mortality as well so muscle plays a very important role so make the most of the opportunity that you have to exercise whilst you're young and fit and try and keep that muscle mass as high as possible