1 00:00:03,735 --> 00:00:07,187 We talked about how there's an efferent and an afferent arteriole. 2 00:00:07,187 --> 00:00:14,292 This is the afferent arteriole, going towards the glomerulus, there's a whole clump of blood vessels here. 3 00:00:14,292 --> 00:00:18,537 There's the efferent arteriole which leaves that clump of blood vessels. 4 00:00:18,537 --> 00:00:23,803 Those blood vessels we know are gonna be surrounded by Bowman's capsule. 5 00:00:23,803 --> 00:00:26,435 We named all the different parts of the nephron. 6 00:00:26,435 --> 00:00:30,637 The proximal convoluted tubule, the loop of Henle, 7 00:00:30,637 --> 00:00:39,970 and this is the distal convoluted tubule. I'm drawing it in between the afferent and efferent arteriole on purpose. 8 00:00:39,970 --> 00:00:47,901 This is where all the different distal convoluted tubules meet up into that collecting duct. 9 00:00:47,901 --> 00:00:53,803 In this section, in this little video, I want to expand on this little piece. 10 00:00:53,803 --> 00:00:58,470 Where the efferent and afferent arteriole are coming together into that glomerulus 11 00:00:58,470 --> 00:01:02,614 between that there's that distal convoluted tubule. 12 00:01:02,614 --> 00:01:06,736 Just keep that picture in mind as I start expanding this drawing. 13 00:01:06,736 --> 00:01:15,504 Over here we have the afferent arteriole, I'm gonna start drawing it, I have enough space here. 14 00:01:15,504 --> 00:01:18,343 Something like that. 15 00:01:18,343 --> 00:01:31,531 These are the endothelial cells that are lining that blood vessel, that arteriole. 16 00:01:31,531 --> 00:01:41,302 On this side we have the same endothelial cells of course, but now it's leaving the glomerulus. 17 00:01:41,302 --> 00:01:54,768 We've got coming and going, over here is the efferent arteriole. 18 00:01:54,768 --> 00:01:58,806 The other one is of course the afferent arteriole. 19 00:01:58,806 --> 00:02:05,169 I'm gonna reverse that arrow, just so there's no confusion about the direction of the blood flow. 20 00:02:05,169 --> 00:02:08,434 I don't want you to be confused about where the blood is going. 21 00:02:08,434 --> 00:02:15,021 It's gonna be going like that and this is the afferent arteriole. 22 00:02:15,021 --> 00:02:18,543 I've got my blood vessels labeled. 23 00:02:18,543 --> 00:02:24,571 Between the two I also have the distal convoluted tubule, so let's draw that in. 24 00:02:24,571 --> 00:02:30,938 This are the cells surrounding the distal convoluted tubule. 25 00:02:30,938 --> 00:02:36,974 There are some very special cells in here, I'm gonna draw them in a different color. 26 00:02:36,974 --> 00:02:40,836 They are the macula densa cells. 27 00:02:40,836 --> 00:02:46,879 They're part of the tubule, but they're very special, so I'm gonna draw them for that reason. 28 00:02:46,879 --> 00:02:56,069 This is the distal convoluted tubule. 29 00:02:56,069 --> 00:03:00,020 And in green are the macula densa cells. 30 00:03:00,020 --> 00:03:04,301 I'm throwing a lot of names at you and I want you to start feeling comfortable with these names, 31 00:03:04,301 --> 00:03:11,141 because they're gonna be used quite a bit. 32 00:03:11,141 --> 00:03:19,143 It's not particularly hard once you get used to the language, but I know it can be confusing to see all these funny words thrown at you. 33 00:03:19,143 --> 00:03:27,369 The next thing I want you to think back about and remember is that arterioles don't just have one layer. 34 00:03:27,369 --> 00:03:30,146 We know that arterioles have multiple layers. 35 00:03:30,146 --> 00:03:34,703 The inner layer, the tunica intima, is the endothelial cells, we know that. 36 00:03:34,703 --> 00:03:41,604 There's also smooth muscle cells. We know that there's also a layer called the tunica media. 37 00:03:41,604 --> 00:03:44,912 That's here, with smooth muscle cells. 38 00:03:44,912 --> 00:03:49,038 I'm gonna try to draw some smooth muscle cells right there. 39 00:03:49,038 --> 00:03:51,972 We have a layer of these smooth muscle cells. 40 00:03:51,972 --> 00:03:59,809 If you look closely under a microscope, you'll see that there are also some interesting cells right here. 41 00:03:59,809 --> 00:04:05,036 I'm drawing them in blue, just to highlight that they're different. 42 00:04:05,036 --> 00:04:09,204 They are actually very similar to smooth muscle cells. 43 00:04:09,204 --> 00:04:13,708 In a way they're specialized smooth muscle cells. 44 00:04:13,708 --> 00:04:17,703 Let me label these two cell types that I've drawn for you. 45 00:04:17,703 --> 00:04:26,437 Smooth muscle cells, they're on the afferent arteriole side. 46 00:04:26,437 --> 00:04:31,805 You'll see them a little bit on the efferent arteriole side as well, but mostly on the afferent arteriole side. 47 00:04:31,805 --> 00:04:39,204 Smooth muscle cells. Then you have these juxtaglomerular cells. 48 00:04:39,204 --> 00:04:41,808 Juxta, talk about a funny word... 49 00:04:41,808 --> 00:04:45,978 Juxtaglomerular cells. 50 00:04:45,978 --> 00:04:49,304 All right, so the juxtaglomerular cells are there. 51 00:04:49,304 --> 00:04:52,768 If you looked under a microscope, they'd be full of granules. 52 00:04:52,768 --> 00:04:58,536 Sometimes they're even called granular cells. 53 00:04:58,536 --> 00:05:06,101 Let me draw in some granules just to remind you that's what people see under a microscope. 54 00:05:06,101 --> 00:05:09,351 Little green granules in this case. 55 00:05:09,351 --> 00:05:13,903 I'll put them into all of them. 56 00:05:13,903 --> 00:05:21,436 You know that these cells are on both sides of the vessel, because of course we cut it longways, 57 00:05:21,436 --> 00:05:24,812 so we're just looking as if it's disconnected. 58 00:05:24,812 --> 00:05:29,973 But these two sides are obviously touching, if you thought of it in three dimensions. 59 00:05:29,973 --> 00:05:36,036 Now I've talked about four cell types, let's round it up with a last cell type. 60 00:05:36,036 --> 00:05:42,133 This is in orange now, these are the mesangial cells. 61 00:05:42,133 --> 00:05:45,638 Mesangial cells are there for structure. 62 00:05:45,638 --> 00:05:59,033 They're really there to hold the whole thing together so that the blood vessels and the nephron are in close contact. 63 00:05:59,033 --> 00:06:04,536 So that they're structurally sound. Think of them as being there for support reasons. 64 00:06:04,536 --> 00:06:09,860 These are the mesangial cells. 65 00:06:09,860 --> 00:06:18,340 Combined, if you think about all this stuff together, remember this is all the white box in the little picture blown up. 66 00:06:18,340 --> 00:06:24,905 If you think about all this stuff together, the macula densa cells, the endothelial cells, the smooth muscle cells, 67 00:06:24,905 --> 00:06:35,203 the juxtaglomerular cells and the mesangial cells, put together, this whole thing is the juxtaglomerular complex. 68 00:06:35,203 --> 00:06:46,180 Or apparatus rather, the juxtaglomerular apparatus. 69 00:06:46,180 --> 00:06:54,512 Kind of a funny word, but it's how people refer to all these cells, the juxtaglomerular apparatus. 70 00:06:54,512 --> 00:07:02,538 The key here is to remember that the goal of the juxtaglomerular apparatus is to release renin. 71 00:07:02,538 --> 00:07:07,277 Think about where renin is. I mentioned these little granules here. 72 00:07:07,277 --> 00:07:13,037 These are actually each gonna be loaded with renin. 73 00:07:13,037 --> 00:07:21,236 These little granules dump themselves into the vessels, this is your renin. 74 00:07:21,236 --> 00:07:28,141 That renin is gonna make its way into the afferent arteriole, just like I drew it, 75 00:07:28,141 --> 00:07:30,578 then it's gonna make its way through the glomerulus. 76 00:07:30,578 --> 00:07:36,804 On the other and it's gonna sprinkle out and go into the efferent arteriole. 77 00:07:36,804 --> 00:07:38,569 That's the way renin gets released. 78 00:07:38,569 --> 00:07:48,478 What we hadn't figured out yet, what we hadn't said, is how, why would the juxtaglomerular apparatus release renin. 79 00:07:48,478 --> 00:07:50,172 What is the trigger? 80 00:07:50,172 --> 00:07:56,869 Let's figure out what are the key triggers for the release of renin. 81 00:07:56,869 --> 00:07:57,937 What are the triggers? 82 00:07:57,937 --> 00:08:02,264 There are three actually. Three common ones we know. 83 00:08:02,264 --> 00:08:12,774 One is simply low blood pressure. This cells are gonna feel mechanically less blood pressure. 84 00:08:12,774 --> 00:08:18,137 They're gonna say 'What's going on here? Pressure is low, we've got to do something about it.' 85 00:08:18,137 --> 00:08:20,304 'We're gonna release renin.' 86 00:08:20,304 --> 00:08:24,875 So one trigger would be low blood pressure. 87 00:08:24,875 --> 00:08:31,835 That's the first one and it's actually directly sensed by the juxtaglomerular cells. 88 00:08:31,835 --> 00:08:37,180 That's actually sensed right here. I'm gonna draw a 1 for that. 89 00:08:37,180 --> 00:08:42,364 The second trigger is a nerve cell trigger. 90 00:08:42,364 --> 00:08:44,703 Actually I haven't even drawn that in for you yet. 91 00:08:44,703 --> 00:08:54,537 Remember that this is a blood vessel, right here, with our two layers, our endothelial layer and our tunica media layer. 92 00:08:54,537 --> 00:08:58,849 There's also an external layer, the tunica externa. 93 00:08:58,849 --> 00:09:06,139 We also have a blood vessel here, these mesangial cells, they're also specialized smooth muscle cells. 94 00:09:06,139 --> 00:09:13,802 We have these layers of blood vessels and the two blood vessels are kind of merging and fusing right here. 95 00:09:13,802 --> 00:09:16,806 They're coming together right here. 96 00:09:16,806 --> 00:09:24,877 In this external layers you actually have, I'm gonna draw it in yellow, you have these little nerve endings. 97 00:09:24,877 --> 00:09:30,370 Remember that nerves can end in that layer, the external layer. 98 00:09:30,370 --> 00:09:38,700 You have the sympathetic nerve endings. 99 00:09:38,700 --> 00:09:44,967 They come and sit with their nerve endings right on the juxtaglomerular cells. 100 00:09:44,967 --> 00:09:52,934 They're sitting right there and when they fire, that's gonna make the JG cells want to dump their renin. 101 00:09:52,934 --> 00:10:01,344 So the second trigger is sympathetic nerves. 102 00:10:01,344 --> 00:10:05,520 Now there's one more trigger, the third trigger. 103 00:10:05,520 --> 00:10:10,700 This one is actually a little distance away. 104 00:10:10,700 --> 00:10:13,036 It's the macula densa cells. 105 00:10:13,036 --> 00:10:15,686 I mentioned them earlier and I said that they're special. 106 00:10:15,686 --> 00:10:20,469 I haven't really gotten into why they're special. Let me tell you what happens. 107 00:10:20,469 --> 00:10:25,972 What happens is these macula densa cells, they're sitting there in the distal convoluted tubule, 108 00:10:25,972 --> 00:10:30,746 sampling what comes through. They're just kind of feeling what comes through. 109 00:10:30,746 --> 00:10:33,312 They're seeing sodium come through. 110 00:10:33,312 --> 00:10:38,581 They're checking and checking, is there a lot of sodium coming through, or a little bit of sodium. 111 00:10:38,581 --> 00:10:43,200 When they start sensing that the sodium content, that the amount of sodium 112 00:10:43,200 --> 00:10:47,238 coming through that distal convoluted tubule is really quite low, 113 00:10:47,238 --> 00:10:50,702 when they start feeling like not too much sodium is coming through, 114 00:10:50,702 --> 00:10:54,514 they start thinking to themselves 'Why is this happening?' 115 00:10:54,514 --> 00:10:57,005 If you think about it, you can figure it out too. 116 00:10:57,005 --> 00:11:02,472 If there is not a lot of sodium here, that's probably because there's not a lot of sodium here. 117 00:11:02,472 --> 00:11:06,428 And that could be because there's not enough sodium here or here. 118 00:11:06,428 --> 00:11:10,691 So really, when the distal convoluted tubule senses low sodium, 119 00:11:10,691 --> 00:11:20,194 it's probably related to the fact that not enough sodium is getting in at the getgo, at the point of filtration. 120 00:11:20,194 --> 00:11:24,076 And that could be a reflection of low blood pressure. 121 00:11:24,076 --> 00:11:35,270 So when the macula densa cells sense low sodium levels, what they're sensing is low pressure in the glomerulus. 122 00:11:35,270 --> 00:11:41,403 So if there's low pressure in the glomerulus, our glomerulus right here, 123 00:11:41,403 --> 00:11:48,602 they think 'Ok,that's probably the reason our sodium levels are low.' 124 00:11:48,602 --> 00:11:54,120 'Let's send a signal out to the juxtaglomerular cells.' 125 00:11:54,120 --> 00:12:04,444 Low sodium in the macula densa, picked up by the macula densa rather. 126 00:12:04,444 --> 00:12:09,747 It means that the filtration pressure in the glomerulus was too low. 127 00:12:09,747 --> 00:12:16,646 So what they decide to do, let me find a new color, maybe something like this. 128 00:12:16,646 --> 00:12:21,976 They send a little messenger. 129 00:12:21,976 --> 00:12:26,313 I'll do my messenger in orange. 130 00:12:26,313 --> 00:12:31,306 They send a messenger to go over to the juxtaglomerular cells. 131 00:12:31,306 --> 00:12:38,670 That messenger is a little molecule called prostaglandin. 132 00:12:38,670 --> 00:12:40,520 It's a local messenger. 133 00:12:40,520 --> 00:12:46,311 It really doesn't act far away from these cells, it just acts locally. 134 00:12:46,311 --> 00:12:54,848 This local hormone, it's sometimes called a paracrine hormone, I'll write that here, paracrine hormone, 135 00:12:54,848 --> 00:13:03,137 is going to send a signal from the macula densa cells over to the juxtaglomerular cells. 136 00:13:03,137 --> 00:13:09,636 They say 'Hey, there's a trigger, we sensed low sodium and we think it's because of low blood pressure.' 137 00:13:09,636 --> 00:13:11,936 'Why don't you go and do something about it?' 138 00:13:11,936 --> 00:13:15,014 So those are the three triggers. 139 00:13:15,014 --> 00:13:18,431 Actually I don't think I've labeled them well. 140 00:13:18,431 --> 00:13:21,681 This is trigger number two and this is trigger number three. 141 00:13:21,681 --> 00:13:29,043 These are the three triggers that will make the renin get released into our blood stream. 142 00:13:29,043 --> 00:13:33,438 This is a picture of renin, this is a picture of the molecule. 143 00:13:33,438 --> 00:13:38,670 I've actually already drawn kind of like a pacman-like shape around it. 144 00:13:38,670 --> 00:13:47,020 When I talk about renin coming out of the juxtaglomerular cells, you get a sense of what it actually looks like. 145 00:13:47,020 --> 00:13:50,571 This is a three dimensional figure of this protein. 146 00:13:50,571 --> 00:13:54,601 Keep in mind this is a protein hormone. 147 00:13:54,601 --> 00:14:03,137 Meaning it's a protein that has the ability of letting one cell talk to other cells at a distance. 148 00:14:03,137 --> 00:14:05,105 This is what that renin looks like. 149 00:14:05,105 --> 00:14:09,000 We'll discuss more about how renin works in the next video.