Neuromuscular Junction

the neuromuscular Junction is basically the intersection between a muscle fiber and a nerve specifically we're talking about this area shown there in the white box if we if you can imagine zooming in on this area this is what you would see you would see the nerve terminal entering the muscular Junction and specifically when we talk about this we talk about things like a presynaptic and postsynaptic area this is no different than any other neural connection but it's neuromuscular because it connects a neuron to a muscle now when you look at this diagram the things that we're going to be focusing on today are labeled as three and four three is acetylcholine and four is the nicotinic acetylcholine receptor so under normal circumstances acetylcholine will flow out of the presynaptic nerve terminal and bind to its receptor on the postsynaptic membrane we're gonna simplify this today but this is what this video is all about because this is the basis for all of the physiology that we're going to talk about so if I simplify this drawing even more this is what we're talking about the presynaptic nerve terminal and the postsynaptic membrane this is the neuromuscular Junction now under normal circumstances you'll have a neurotransmitter in this case acetylcholine shown there as red circles and the acetylcholine will leave the presynaptic nerve terminal and bind to its nicotinic acetylcholine receptor on the postsynaptic membrane shown here as red diamonds this is what happens normally I'm just going through normal physiology when these neurotransmitters bind to their receptors you generate an action potential which you see here which travels down through the muscle and helps coordinate muscular contraction this is very important for normal gait normal muscular tone etc but what happens when this doesn't go as planned so let's talk about an example instead of acetylcholine shown as red circles let's say that we give a drug and the drug is going to bind to it the nicotinic acetylcholine receptor on the postsynaptic membrane shown here the drug will be illustrated by light blue stars these light blue stars mimic acetylcholine because they're going to bind to the nicotinic acetylcholine receptor so it flows across and binds to the nicotinic acetylcholine receptor when it does that this particular drug drugs job is to inhibit the nicotinic acetylcholine receptors so it does this by just occupying it it's it's it's fat ass down in the receptor and says I like it here we're gonna block all activity at this receptor what happens when you do that is you get a fade in activity so instead of generating a normal action potential the activity at the receptor fades quickly over time and blocks all impulses this is the mechanism of nondepolarizing nor muscular blockers I will talk about this more in depth as we go on but I just want to kind of plant the seed now that a nondepolarizing neuromuscular blocker will bind to the nicotinic acetylcholine receptor and cause a fade in activity without depolarizing the receptor now what happens if we have a different substance shown here as yellow stars I do apologize because I understand that the yellow is very bright and may be difficult for you to see but there are yellow stars there now these yellow stars are also a drug that are neuromuscular blockers but they act differently they flow across to the nicotinic acetylcholine receptor and instead of blocking the nicotinic acetylcholine receptor they constantly stimulate it and when they do that they bind to the receptor and supercharge the postsynaptic membrane and by doing that they cause action potentials to fire over and over and over and over again by doing this they essentially tire out the postsynaptic membrane and at first they'll cause a diminished but constant action potential but then that will quickly turn into a fading over time this is the mechanism of a depolarizing nor muscular blocker so again the difference between depolarizing and nondepolarizing is that the depolarizing neuromuscular blocker will depolarize and cause sustained action at the receptor which is constant but diminished and then that quickly progresses into a fading of activity as the receptor and the postsynaptic membrane get tired over time so let's talk about the differences here because this is what's really high-yield for step one and level one depolarizing neuromuscular blockers are have two phases of action the first phase is that constant phase and these lines that you see in orange this is how this will be shown to you when you take tests and samms that basically it's a snapshot of the action at the postsynaptic membrane phase one is the constant but diminished action the receptor is firing the postsynaptic membrane is undergoing action potentials and activity it because it's being depolarized hence the name depolarizing neuromuscular blocker over time though that action will fade and mimic what you see in a nondepolarizing neuromuscular blocker so the nondepolarizing neuromuscular blocker only has one step and it's that fade the depolarizing has two phases phase one which is constant but diminished and phase two which is the fade so phase two of depolarizing and the overall action of nondepolarizing are identical they're both the fades the only difference is that depolarizing has a constant but diminished phase one where you get constant activity at the receptor so think of depolarizing as causing activity but tiring out the receptor and think of nondepolarizing as just sitting its fat ass down on the receptor and blocking all activity depolarizing neuromuscular blockers there's one that you need to know and it's succinylcholine everything else is nondepolarizing so they all end with curium curium is nondepolarizing and succinylcholine is depolarizing we'll talk about the pneumonic after this slide depolarizing has no antidote for that phase one so phase one where it's the constant but diminished activity at the receptor there's no antidote to reverse that but if someone overdoses let's say on a nondepolarizing normal muscular blocker you just give them an acetylcholine esterase inhibitor and that is the antidote so think about it you're blocking acetylcholine activity if you give them an acetylcholinesterase inhibitor you're inhibiting the thing that usually breaks down acetylcholine so basically acetylcholine is dis inhibited and therefore total levels of acetylcholine are increased that is why acetylcholinesterase inhibitors are the antidote for nondepolarizing neuromuscular blockers the super super high yield thing on this slide besides just those orange lines is that if you give someone a depolarizing normal muscular blocker there are three things or three side effects you should look for the first is fasciculations because that receptor is being constantly stimulated and depolarized you're gonna see this manifest as fasciculations or small twitches in the muscle again the muscle is active an action potential is generated you are depolarizing the receptor because of this we expect to see things like fasciculations and muscular activity the really really high yield one is hyperkalemia and especially in patients who have profound tissue damage or are recent victims of something like a burn anytime you depolarize a muscular receptor you cause activity at that receptor now think about it this way if you have muscles acting over and over and over again the muscle breaks down and releases the the the intramuscular potassium that flows out into the rest of the body this is basically the pathophysiology of something like rhabdomyolysis so think about it the same way here when you depolarize over and over and over again you cause release of potassium so in somebody who is has a lot of muscular injury was recently burned etc look for hyperkalemia on tests they might try to get you with that by showing you an EKG and asking you you know to identify peaked peaked waves due to hyperkalemia maybe they'll give you a patient who goes into new onset kidney failure and they're hinting at rhabdomyolysis there are lots of ways that they can get after hyperkalemia so keep that in the back of your mind when someone gets something like succinylcholine which is a depolarizing neuromuscular blocker and finally malignant hyperthermia anytime you give someone a depolarize ignore a muscular blocker they are at risk for developing malignant hyperthermia understand how you treat it know about dantrolene etc etc so those are the main differences that you should keep in mind for your test depolarizing versus nondepolarizing the mnemonic in the way that I remember this is that I say depolarizing sucks and ND curium so sucks for succinylcholine it sucks because it can cause fasciculations hyperkalemia rhabdomyolysis and malignant hyperthermia sucks reminds me of succinylcholine and sucks reminds me that the depolarizing neuromuscular blocker just sucks all of the life out of the receptor by stimulating it for so long ND curium the nd obviously me of nondepolarizing and curium is obviously all of those agents and in curium the other thing is that curium sounds like curious and I find it curious that these that these agents don't simulate any action at the receptor in fact they just cause that fade effect which is very curious so depolarizing agent sucks and ND curium are curious agents that don't do anything so those are the major major differences in everything that you should keep in mind for test day if you really are struggling with brain space know the difference between the graph of the lines so those orange lines at the top know that depolarizing has two phases and then know the side effects of the did polarizing agents such as hyperkalemia malignant hyperthermia and muscular fasciculations now let's talk about some things or some pathology that can occur when we have problems at the neuromuscular Junction so to do this I'm gonna highlight two things that we already talked about in orange you see acetylcholine that gets released from the presynaptic nerve terminal on the end plate there you see the nicotinic acetylcholine receptor on the postsynaptic membrane this is where the acetylcholine binds to and under normal circumstances you'll have a properly generated action potential what you see at the top there in blue is a calcium channel and we haven't talked about this yet so let's just briefly go over this calcium channels allow calcium to flow into the presynaptic nerve terminal and calcium is really really important for the release of vesicles in which neurotransmitters are stored so not just acetylcholine but every neurotransmitter right like dopamine norepinephrine etc they all require calcium to allow the vesicles in which those neurotransmitters are stored to dump the neurotransmitters in the nerve Junction so calcium must be in the presynaptic nerve terminal and in other words we need calcium to flow from the outside into that presynaptic area where the acetylcholine will be stored so that's why the calcium channel is very important there are three disease processes that you should know that can occur when any one of these three processes get messed up so I'm going to use the color coding to make this really simple we have lambert-eaton syndrome botulism and myasthenia gravis lambert-eaton syndrome corresponds to the calcium-channel botulism to acetylcholine release and myasthenia gravis to the postsynaptic nicotinic acetylcholine receptor so let's talk about the differences here and this is how we'll wrap up lambert-eaton syndrome is due to the destruction of the presynaptic calcium channels botulism occurs when you have problems due to acetylcholine release myasthenia gravis occurs when you have immune attack against the postsynaptic nicotinic acetylcholine receptors so let's pause for one second here the first thing I want to point out is the difference between lambertian and myasthenia gravis because these can sound similar on tests when they go after this they like to go after the mechanism here so know that lambert-eaton syndrome is presynaptic and it's the calcium channel know that myasthenia gravis is postsynaptic and it's the nicotinic acetylcholine receptor big difference there pre versus post synaptic lambert-eaton syndrome and myasthenia gravis are both type 2 hypersensitivity reactions just good to keep in the back of your mind botulism is caused by a heat label enterotoxin now perhaps the highest yield thing on this slide are the associations so know that lambert-eaton syndrome is associated with small cell lung cancer note that botulism is associated with eating honey and know that myasthenia gravis is associated with the thymoma if they give you a thymoma they want myasthenia gravis if they give you lambert-eaton syndrome they're gonna say what should you do you know maybe a lung x-ray or CT whatever because you want to think about the small cell lung cancer they're gonna talk about honey if they're going for botulism so mechanism association and pre or post synaptic are very important with these disease processes now I'm not gonna go through the symptoms individually obviously we're talking about the neuromuscular Junction so there's gonna be problems with things like being super you know flax so there's going to be problems with coordination of proper muscular contractions so you can be contracted too much you can be way too lacks etc etc so you know review the symptoms on your own time I'm here to give you the high yields the associations what you need to think about on test day but that's it guys that's the neuromuscular Junction that's neuromuscular blockade that's depolarizing versus nondepolarizing neuromuscular blockers remember the depolarizing agent sucks and the nondepolarizing agents and d curium the curious and d agents that don't do anything that is neuromuscular blockade

Channel: Dirty Medicine

Views: 74,496

Rating: 4.9353447 out of 5

Keywords: USMLE, COMLEX, Step, Boards, Mnemonics, High, Yield, DirtyUSMLE, Neuromuscular Junction, Neuromuscular Blockade, Succinylcholine, Depolarizing, Non-Depolarizing, Rhabdomyolysis, Hyperkalemia, Malignant Hyperthermia, Acetylcholine, Nicotinic Receptor, Myasthenia Gravis, Lambert-Eaton Syndrome, Botulism, Botulinum Toxin, Calcium, Potassium, Action Potential, Neuron, Phase 1, Phase 2, Blockade, Acetylcholinesterase Inhibitor, Physiology

Id: Bvt5EbOZhEo

Length: 13min 41sec (821 seconds)

Published: Sat Jul 21 2018