Research Week 2 Part 1.docx

In Unit 1.9, we will look at a review of neuroscience for registered respiratory therapists. This is an opportunity to review selected concepts in preparation for the clinical research practicum in the Spinal Cord Injury Center at the Tampa VA. I know that you've already had neuroadamant neurophysio...

In Unit 1.9, we will look at a review of neuroscience for registered respiratory therapists. This is an opportunity to review selected concepts in preparation for the clinical research practicum in the Spinal Cord Injury Center at the Tampa VA. I know that you've already had neuroadamant neurophysiology in your A&P course. This is just a review of selected concepts to enable you to refresh these concepts so that as we enter the Spinal Cord Injury Center and we deal with patients that have neurotrauma and neurodegenerative disorders, we'll be able to understand more readily what their main problems are from a neurological standpoint. We want to look at the astrocyte, which is a type of glial cell as a key cell in the central nervous system. We want to also identify some cardiopulmonary centers that we have in the brainstem, again, by way of review. And we want to explain the role that an increase in intracranial pressure plays in intracranial pathology. I'm sure you recall the normal anatomy of a neuron. You remember that, of course, there is a cell soma or a cell body. There's an axon that leads from the cell soma and goes out to an area of arborization shown here, at the end of which there are terminal glutons with neurotransmitter vesicles inside. And we know that this soma, upon receiving the appropriate intensity of signals and the appropriate pattern of signals, will generate an action potential that will propagate down the axon to the synaptic telodendria, all the way out to the terminal glutons, whereupon the electrical signal is converted into a chemical signal in the form of a neurotransmitter going out across the synapse and to the postsynaptic membrane. And here we see an axon, and of course there's myelin that is shown in and around where the axon is. These areas of myelin, as shown here, are important because they insulate the axon. And not only that, but there are these little intervals called the nodes of Ranvier that are actually devoid of myelin. And what happens is that as the action potential propagates down the axon, that action potential actually jumps from one node to the next. Well, overall what that means is that the speed with which the action potential is able to propagate down the axon is increased dramatically just because there is this myelin sitting on top of the axon. Were it not for this myelin, the action potential would be very slow, and for all intents and purposes that would mean that there would be no neural function, even if the neuron itself has no real significant cellular problems and is basically not diseased in any way or traumatized in any way. So the presence of this myelin is crucial to the function of a given nerve. Another important organelle is the Golgi apparatus. You can see the Golgi apparatus here. Coming off of the Golgi are these little transport vesicles that use microtubules as a highway for not only sending neurotransmitter-filled vesicles all the way out to the presynaptic cleft, but when those vesicles are empty, bringing those vesicles back toward the cell so that they can be reprocessed. So these microtubules shown here as these little blue tubes are very important. And I'm actually going to give you later on a slide that talks about the importance of these microtubules after someone has had a spinal cord injury. And we just mentioned moments ago something about the terminal boutons and how they're at the very end of the synaptic telodendria. And here you can see a cartoon representation of that. Here's the mitochondria that we just saw on the electron microscope and these little transmitter vesicles with neurotransmitter inside of them. And then on this side, we have the actual electron microscope that supports that and shows that in reality. And this is a false color image, so we don't really have these colors in the real animal tissue. But by dyeing the tissue in various ways, we can see this a little better. And you can see that these neurotransmitter vesicles are coming right up to the cleft over here. They're going to give up their neurotransmitter. The neurotransmitter will go across to the other side and start an action potential on the other side. So you'll get an action potential from one neuron going through the synaptic cleft to the next neuron so that we get propagation of action potentials from neuron to neuron to neuron. This is what we strive to fix when we have an individual that has a spinal cord injury or we have an individual that has ALS. And what's happening, of course, is that these neurons are no longer functioning the way that they should. But it's important, first of all, to understand what's normal before we can delve into what's abnormal about those types of patients. Well, in this slide, I have a cartoon of how astrocytes support neurons both physically as well as physiologically. And let me explain what I mean by that. We know that neurons are very important in the brain. We know that astrocytes are very important in the brain. What we didn't know until fairly recently is that the great majority of the cells in the brain are not neurons. They're actually astrocytes. And astrocytes are extremely important in keeping neurons functioning well. Now, you'll notice that in addition to the astrocyte and in addition to the neuron, over to the right side of the cartoon, there is a capillary. And what I've done is I've placed a red arrow that shows how the blood is coursing through the inside of the capillary. If you look at the astrocyte for just a minute, you're going to see that there are extensions from the astrocyte, and they go all the way up to where the capillary is. As a matter of fact, if you follow that extension, you're going to see that it ends in something called an end foot. In addition to that, there are extensions from the astrocyte that proceed to the neuron. And once again, there are end feet there. So in essence, this astrocyte is connecting to the capillary, and it's connecting to the neuron. But actually, there's much more than that. It's actually connecting the capillary to the neuron, and it's connecting the neuron to the capillary. Let me explain. As oxygen courses through the capillary, when oxygen gets to an end foot, it actually enters that end foot, goes down the extension to the astrocyte, and the astrocyte then is responsible for delivering that oxygen to the neuron. Conversely, when the neuron produces carbon dioxide as a result of its metabolism, the carbon dioxide enters the end foot that is attached to it, and proceeds into the astrocyte, and then the astrocyte releases that carbon dioxide into the capillary. So really, what we have here is a guardian. The astrocyte can be thought of as being a guardian for the neuron. We have a more technical term for this, and it's called the blood-brain barrier. I know that you've heard of the blood-brain barrier before, particularly in regards to pharmacology. Well, the astrocyte is literally protecting the neuron from foreign substances that would otherwise be toxic to the neuron. But it also provides two other functions. It acts as packing material, keeping the neuron where it needs to be, and it also provides the physiological services that I referred to just a moment ago. One last item that's of key importance, and that is as long as there is blood flowing through the capillary, this system continues to operate normally. Once there is a decrease in blood flow through the capillary, if it's for a short period of time, for example, a minute, two minutes, three minutes, things usually don't change very dramatically. However, if the blood flowing through the capillary is reduced significantly for, say, three and a half, four minutes, four and a half minutes, perhaps five minutes, the astrocyte swells, and swells irreversibly. And that's why down at the lower left we have the term "no reflow," because this astrocyte swells so much that its astrocytic end feet literally strangle the capillary, not allowing any additional blood flow after that point in time. So if you're going to cut off the blood supply to this section of the brain, you can do it for about four minutes. But if you do it for more than four minutes, it will lead to irreversible changes in the brain. And this is key to understand, because so many of the pathologies that are present, not just in patients that have neurotrauma, but also in patients that have neurodegeneration, are based on what I have just discussed with you. In this view of the brain, there are a lot of different things that we could study, but really I'd like you to focus on just two, because we'll have occasion to talk about these within the context of not only individuals who have trauma, but also individuals who have different types of neurodegenerations. One of them is the primary motor cortex shown here, and right behind it, the primary somatosensory cortex, or the sensory cortex. When you have the motor cortex shown here and the sensory cortex shown here, right between those two, there is a deep gorge that we refer to as the central sulcus. And it turns out that it's from the primary motor cortex that we have all motor function emanating and coursing down to the spinal cord, and of course, from there all the way out to the musculature. I'm sure that's a review for you. When you, of course, have sensory information, that sensory information comes back from the spinal cord into the brain and more specifically ends up in the primary somatosensory cortex. So basically, these are two areas that begin the journey of action potentials out to the periphery, and then sensory information is delivered back via afferent fibers back into the sensory part. So it's motor and sensory. I just showed you the way that motor fibers and sensory fibers traverse through the brain. I showed them to you as straight lines. In reality, you realize that they're not really straight lines. From the motor centers, we're going to have fibers that course to the thalamus, which is a switchboard of brain, through the midbrain, past the pons, medulla, and down into the spinal cord. And of course, the sensory information is going to come right back via sensory tracts that will basically retrace this pathway back up to the thalamus, and from there project up to the sensory areas. So obviously, it's not as basic as I made it up to be in the last slide, but I think you realize that it's just an oversimplification to help us to just review a little bit. Let's look at respiratory centers in the brainstem. There are three main centers that you should be familiar with. Again, this is all by way of review. There is the ventral respiratory group shown here, and you can think of this group as being sort of a sinoatrial node of the brainstem in the sense that this is where breathing signals are initiated. This is where they come from. There's also a dorsal respiratory group, and the function of the dorsal respiratory group is to basically take information that's coming in from the periphery about carbon dioxide levels, hydrogen ion levels, and so forth, and integrate that information and then send that information forward to the ventral respiratory group so that if, for example, there's an increase in carbon dioxide, the ventral respiratory group will increase its rate or the depth of contraction. Finally, superior to both of those nuclei is the pontine respiratory center, and this pontine respiratory center is responsible for making ventilation nice and easy and smooth. Nice, easy inhalations. Nice, easy exhalations. If that's happening, it's because the pontine respiratory center is making it so. Let's talk about medullary cardiomotor centers. These are very important. Here's the heart, and of course, you and I both know that there are sinoatrial, there's a sinoatrial node, there's an atrial ventricular node, and these have inherent rhythmicity. In other words, these two can initiate contraction of cardiac muscle without any influences. However, we also know that there are, in fact, influences that can increase the rate or decrease the rate of cardiac contraction. And if we look in the medulla, there are actually two nuclei. Here's one nucleus right here, and it's contralateral homolog. Here is another nucleus, and it's contralateral homolog. This particular nucleus shown here is a cardio-inhibitory center. The other one, just adjacent to it, is a cardio-acceleratory center. So you can think of this as the accelerator in your car, and this is the decelerator in your car. And what we find is that when you put your foot on the accelerator, you're going to accelerate the generation of action potentials down a vagus nerve. This vagus nerve is a cranial nerve that courses out to the sinoatrial node and the atrial ventricular node and can cause that, the inhibition or the deceleration of the heart rate. On the other hand, if we have the other nucleus firing, then what will happen is that it will send its action potentials down into the thoracic portion of the spinal cord. That action potential will course out to the sympathetic ganglion, and from the sympathetic ganglion, it will go out to the fibers, accelerating both the sinoatrial node and the atrial ventricular node. So whether it's an accelerated set of signals or a decelerated set of signals, although the heart has its own auto-rhythmicity, the heart also responds to influences from the central nervous system. And that's important to note. Throughout this entire section of the medulla, there are neurons and there are astrocytes that are doing the same types of things that we've talked about previously. Remember the very intimate relationship, functional relationship that occurs between astrocytes and neurons. So if we get a decrease in blood flow for any reason in an area like this, we're going to see aberrant functionalities arising. In other words, we're going to get changes, pathological changes that may in fact affect the heart. With regard to brain trauma, there are two major types of brain trauma that are shown in the upper left. You can see that as this individual moves forward and has some type of accident where he contacts the front part of the cranium, the brain literally moves so fast forward that when it snaps back, it's going to hit the posterior aspect of the brain. And we refer to that as a contracoup injury. This individual hit the front of his head, but in reality, the major part of the damage is not in the front part of the brain, but in fact in the back part of the brain because the brain snaps back inside the cranium and causes extensive damage of the posterior lobe. So we very often refer to this as a coupe/contracoup injury. And these are very, very common in individuals who've been in motor vehicle accidents and falls and so forth. Also associated with such things as blast injuries if you're in a military hospital and you're seeing veteran patients. These types of injuries can also lead to a number of accumulations of blood within the cranium. And I'm showing you some of these in cartoon fashion here. You can see that there is a subdural hematoma that is actually underneath the dura and that accumulation of blood is pushing up against the brain, distorting the brain. When that happens, there are going to be changes in brain function. It's possible to have intracerebral hematoma where you have bleeding into the brain. And as you might guess, if you have an intracerebral hematoma like this, you're going to have changes that occur on the part of the astrocytes as well as the neurons with changes in functionality. If we have an epidural hematoma, same type of thing. In this case, the bleeding is not underneath the dura, but is in fact on top of the dura. Epidural hematomas are quite common, for example, in elderly patients if they fall and or just hit their heads against some type of an object, there will be a small ooze or a small bleed that occurs. And that can lead to not only central nervous system changes, but also behavioral changes as well. Well, in the top diagram, I'm showing you a cross section of brain and you can see that at the very top, you have a cerebral hemispheres. At the bottom, you have the cerebellar portions of the brain. And what is being shown here is a focal accumulation of blood on your right side. So you can see that kind of in a dark fashion, it resembles a, it could be a subdural hematoma, it could be an epidural hematoma. In either case, you can see that there's a shift in the brain. And that is what the problem is. When there's a shift in the brain that way, you'll notice that some portions of the brain are going to herniate downward. You'll notice there's a number two there with an arrow. That is known as UNCAL herniation. In addition to that, you have a number three with a downward arrow. You have a number four with a downward arrow. You have a number one up at the very top that shows a shift from one side of the brain to the other. These are all changes in the directionality of the brain. The brain is actually moving because there's an accumulation of blood that is pushing the brain to move in those directions. One of the problems is that as the brain moves downward, it literally tries to leave the cranium and it's trying to get out of the foramen magnum, that opening that's at the bottom of the cranium. When that happens, there's going to be compression of the brainstem. As you and I both know, inside the brainstem, there are cardiomotor centers, the ones that we studied just a moment ago. If there is long-term compression of these centers, that means that both respiratory and cardiac arrest can occur, leading, of course, to the demise of the patient. It's important to understand this not only at a gross level, as we've just described it, but also at a microscopic level, as we previously described it in the slide where we looked at the extracite and the neuron and the capillary. There are ways that we can monitor the changes that are occurring inside of the brain. There are a number of monitors that can be placed into the skull itself, and you can see these at the lower right. In addition to that, not only do many of these tools monitor the changes in the brain, but they can actually be therapeutic in the sense that we can draw off fluid through some of these monitors in order to decrease the intracranial pressure inside the brain. This is unit 1.10, the second part of neuroscience for RRTs. Here we'll discuss the clinical presentation of upper and lower motor neuron lesions. We'll explain what is meant by C3, C4, and C5, keep the diaphragm alive. We'll look at parasympathetic predominance and its relevance for respiratory care practice, and we'll also discuss how ASIA classifications denote levels of injury in those individuals that have spinal cord injuries. And here we see a vertebral motor unit within which one sees the spinal cord itself. And when you look at the spinal cord, you can see that there are a number of coverings that are around the spinal cord protecting it, one of which is the pia mater, very closely adherent to the spinal cord. There's also an arachnoid mater that is just distal to that. And inside of the arachnoid mater, we have cerebral spinal fluid that actually circulates around and serves as a cushion or as a barrier for any jolts that might occur. Finally, the outermost covering of the spinal cord is the dura mater. And you will remember from anatomy and physiology that the dura mater, the arachnoid mater, and the pia mater are all continuous and confluent with the structures that ascend up from the spinal cord into the brain. If you look at the cross section of the brain that we have here, you can see that it has cerebral spinal fluid that is being produced by the ventricular system inside of the brain. And then this cerebral spinal fluid circulates around the outside of the brain and around the outside of the brain stem and around the outside of the spinal cord as well as through the spinal cord itself. Not only is the cerebral spinal fluid important in terms of mitigating shocks to the central nervous system, but also it offers a nutritive function as well.