1 00:00:01,737 --> 00:00:07,369 The body has a really really cool way of controlling blood pressure. 2 00:00:07,369 --> 00:00:11,137 You'll hear about this RAAS-system. 3 00:00:11,137 --> 00:00:19,404 RAAS stands for Renin Angiotensin Aldosterone System. 4 00:00:19,404 --> 00:00:24,112 Let's go through this RAAS-system, kind of like an overview. 5 00:00:24,112 --> 00:00:31,070 Just looking at where things start from and where things go in terms of cells and hormones. 6 00:00:31,070 --> 00:00:33,940 Those are the two things I want to distinguish between. 7 00:00:33,940 --> 00:00:39,171 This RAAS-system begins with a set of cells. 8 00:00:39,171 --> 00:00:43,335 I'm gonna draw all of my cells as little blue houses, like that. 9 00:00:43,335 --> 00:00:49,469 The hormones they release are gonna be orange messengers. 10 00:00:49,469 --> 00:00:54,737 I'm gonna draw a little messenger, this will be a little person. 11 00:00:54,737 --> 00:01:00,277 The person is the hormone and the blue house is the cell. 12 00:01:00,277 --> 00:01:10,968 The key cell in the RAAS-system is the juxtaglomerular cell. The JG cell. 13 00:01:10,968 --> 00:01:22,469 These JG cells are actually in the kidney, but in a specific location, in the blood vessels. 14 00:01:22,469 --> 00:01:31,882 If you look closely, these JG cells are nothing more than very special smooth muscle cells. 15 00:01:31,882 --> 00:01:37,076 If you look in the blood vessels, they're actually just like smooth muscle cells. 16 00:01:37,076 --> 00:01:41,970 I'm gonna write smooth muscle, just to remind you where they are. 17 00:01:41,970 --> 00:01:46,136 Of course these are in the kidney. 18 00:01:46,136 --> 00:01:49,577 It may not look like a kidney, but that's what it's supposed to be. 19 00:01:49,577 --> 00:01:54,009 The JG cells are releasing a hormone called renin. 20 00:01:54,009 --> 00:01:55,548 When would they do that? 21 00:01:55,548 --> 00:02:02,476 Renin is gonna help us raise blood pressure. 22 00:02:02,476 --> 00:02:08,133 If the juxtaglomerular cells, these little guys, notice the blood pressure is low, 23 00:02:08,133 --> 00:02:12,284 that would be a trigger for releasing renin. 24 00:02:12,284 --> 00:02:20,300 That's the first trigger, low blood pressure. 25 00:02:20,300 --> 00:02:25,442 That's not the only trigger, there are actually 3 triggers. 26 00:02:25,442 --> 00:02:27,640 Let me write down 2 and 3. 27 00:02:27,640 --> 00:02:29,010 Let's go through what they are. 28 00:02:29,010 --> 00:02:38,705 The second trigger is a neighboring cell is actually a sympathetic nerve cell. 29 00:02:38,705 --> 00:02:48,280 We know that sympathetic nerve cells, they fire whenever something big is going on. 30 00:02:48,280 --> 00:02:56,669 For example you're running away from a bear, or let's say you're trying to win a fight, 31 00:02:56,669 --> 00:03:00,505 or let's say you're in a car accident and you start bleeding. 32 00:03:00,505 --> 00:03:07,469 Any sort of major stressor is gonna cause these nerve cells to start firing. 33 00:03:07,469 --> 00:03:11,901 When they fire, that JG cell starts releasing renin. 34 00:03:11,901 --> 00:03:16,052 So the second trigger would be the sympathetics. 35 00:03:16,052 --> 00:03:21,469 The sympathetics, or maybe sympathetic nerves. 36 00:03:21,469 --> 00:03:29,961 If these are your neighboring cells, these little sympathetic nerve cells, because they end right on the JG cells. 37 00:03:29,961 --> 00:03:42,703 Then a little ways away, still in the kidney of course, not touching the JG cells, would be the macula densa cells. 38 00:03:42,703 --> 00:03:47,303 Stay with me for this, these macula densa cells are also in the kidney 39 00:03:47,303 --> 00:03:56,069 and actually they're specifically in the distal tubule of the nephron, so remember the distal convoluted tubule. 40 00:03:56,069 --> 00:04:03,049 They're there, their interesting ability is the ability to sense sodium. 41 00:04:03,049 --> 00:04:12,172 When you have low blood pressure, not a lot of blood is moving through that glomerulus. 42 00:04:12,172 --> 00:04:17,243 Not a lot of blood is moving through the nephron as a result. 43 00:04:17,243 --> 00:04:20,892 A lot of the salt is being reabsorbed. 44 00:04:20,892 --> 00:04:24,003 So by the time it gets to the distal convoluted tubule, 45 00:04:24,003 --> 00:04:31,633 the macula densa cells, they're kind of tasting or sensing the fluid that goes by 46 00:04:31,633 --> 00:04:34,071 and they say 'There's not a lot of salt here.' 47 00:04:34,071 --> 00:04:39,557 They put 2 and 2 together and realize that the reason there's not a lot of salt, is that the blood pressure is low. 48 00:04:39,557 --> 00:04:46,103 So when they don't sense much salt, they say 'Hey, JG cells, wake up!' 49 00:04:46,103 --> 00:04:49,882 'Do something about this, raise blood pressure for us.' 50 00:04:49,882 --> 00:04:54,811 They send a message over in the form of prostaglandins. 51 00:04:54,811 --> 00:04:58,736 Prostaglandins are local messengers. 52 00:04:58,736 --> 00:05:03,911 Unlike renin, which is more of a long distance messenger, prostaglandins act locally. 53 00:05:03,911 --> 00:05:10,399 Actually, lots and lots of cells in our body use prostaglandins to send local messages. 54 00:05:10,399 --> 00:05:22,025 The third trigger, just to summarize it, is low salt in the distal convoluted tubule. 55 00:05:22,025 --> 00:05:30,598 You know specifically that it's the macula densa cells of the convoluted tubule. 56 00:05:30,598 --> 00:05:35,896 So these are the three major triggers for renin release. 57 00:05:35,896 --> 00:05:38,298 This is all happening in the kidney. 58 00:05:38,298 --> 00:05:41,361 That's were all this action is occurring. 59 00:05:41,361 --> 00:05:46,794 But you know there are other organs involved in blood pressure control as well. 60 00:05:46,794 --> 00:05:52,133 The one that is next on our list, is the liver cells. 61 00:05:52,133 --> 00:06:02,191 The liver cells, here we go, a little house for cells, are also making a hormone of their own. 62 00:06:02,191 --> 00:06:08,793 It's gonna meet up with renin in a second and it's called angiotensinogen. 63 00:06:08,793 --> 00:06:20,897 Angiotensinogen is kind of a sleepwalker, if we would zoom in on its face, it would be asleep. 64 00:06:20,897 --> 00:06:23,664 So I'm gonna draw it that way. 65 00:06:23,664 --> 00:06:30,438 It's there and it's moving around the body, but it's not active and that's the key thing, it's not active. 66 00:06:30,438 --> 00:06:39,564 But it needs renin and renin literally chops of a big chunk of angiotensinogen. 67 00:06:39,564 --> 00:06:41,861 And if that doesn't wake you up, I don't know what would. 68 00:06:41,861 --> 00:06:51,684 Angiotensinogen becomes angiotensin I after meeting renin. 69 00:06:51,684 --> 00:06:59,868 So renin is an enzyme that cuts a big chunk of this angiotensinogen protein away. 70 00:06:59,868 --> 00:07:08,432 Angiotensin I is the result. If you'd zoom in on this guys face, it would be awake. 71 00:07:08,432 --> 00:07:11,641 Maybe even a little smile. 72 00:07:11,641 --> 00:07:22,440 Angiotensin I now floats through blood vessels and of course blood vessels have cells lining them. 73 00:07:22,440 --> 00:07:26,161 So let's draw a little house. 74 00:07:26,161 --> 00:07:35,028 These are the endothelial cells. These are the cells that are lining the blood vessel inside. 75 00:07:35,028 --> 00:07:39,027 Classically we used to think that this is almost always happening in the lungs, 76 00:07:39,027 --> 00:07:47,061 but more and more we're realizing that it definitely does happen in the lungs, but it's in other vessels as well. 77 00:07:47,061 --> 00:07:51,595 Endothelial cells in a number of parts of our body, including the lungs, 78 00:07:51,595 --> 00:08:00,461 are able to convert angiotensin I into angiotensin II. 79 00:08:00,461 --> 00:08:06,503 So angiotensin II is formed. 80 00:08:06,503 --> 00:08:11,562 This is also a hormone, so I'll draw this little person. 81 00:08:11,562 --> 00:08:18,775 Angiotensin II is happy as a clown, because angiotensin II has lots of activity. 82 00:08:18,775 --> 00:08:21,892 It's a very very active hormone, it does all sorts of things. 83 00:08:21,892 --> 00:08:23,961 I'm gonna draw that activity now. 84 00:08:23,961 --> 00:08:29,268 Angiotensin II will go out to a number of different places. 85 00:08:29,268 --> 00:08:36,960 I'm gonna draw four arrows, 1, 2 and two little ones, 3 and 4. 86 00:08:36,960 --> 00:08:45,966 It goes to four places and four different cell types are affected by angiotensin II. 87 00:08:45,966 --> 00:08:52,602 Keep in mind, at the beginning of all this, we're trying to raise blood pressure. 88 00:08:52,602 --> 00:09:00,093 Four different cell types are affected and here is the fourth. 89 00:09:00,093 --> 00:09:08,754 The first one over here is smooth muscle cells in the blood vessels. 90 00:09:08,800 --> 00:09:13,804 This is smooth muscle cells all over the body, not just in the kidney. 91 00:09:13,804 --> 00:09:21,509 These smooth muscle cells all over the body are going to contract, they're gonna constrict down. 92 00:09:21,509 --> 00:09:24,564 They're gonna cause increased resistance. 93 00:09:24,564 --> 00:09:32,733 Remember that as the blood vessels constrict, vasoconstrict, that will increase resistance. 94 00:09:32,733 --> 00:09:35,797 That's one effect. 95 00:09:35,797 --> 00:09:45,176 In a different cell type all together, in the kidney cells, you actually have the ability to, 96 00:09:45,176 --> 00:09:50,095 angiotensin II makes these kidney cells hold on to more water. 97 00:09:50,095 --> 00:09:53,253 So you have more volume. 98 00:09:53,253 --> 00:09:58,861 It helps the kidney to hold on to more water and more volume. 99 00:09:58,861 --> 00:10:03,194 Think about it in terms of stroke volume. It's gonna increase stroke volume. 100 00:10:03,194 --> 00:10:09,101 So you have increased resistance and now increased stroke volume. 101 00:10:09,101 --> 00:10:13,261 Those are two cell types for angiotensin II to act on. 102 00:10:13,261 --> 00:10:17,761 It also acts on a couple of glands. 103 00:10:17,761 --> 00:10:21,577 I'm gonna try to draw for you the pituitary gland. 104 00:10:21,577 --> 00:10:28,095 This pituitary gland is sitting at the base of the brain. 105 00:10:28,095 --> 00:10:38,234 This gland is called that because it secretes hormones as well, actually it's sending out messengers as well. 106 00:10:38,234 --> 00:10:44,260 Here's a little hormone, again in orange, remember all our hormones are in orange. 107 00:10:44,260 --> 00:10:50,418 This one is called ADH. AntiDiuretic Hormone. 108 00:10:50,418 --> 00:10:58,231 That ADH does some of the same stuff, at the end of the day, that angiotensin II will do. 109 00:10:58,231 --> 00:11:01,761 In that it will increase resistance of blood vessels 110 00:11:01,761 --> 00:11:08,003 and it will also increase volume by making the kidney hold on to more water. 111 00:11:08,003 --> 00:11:13,626 The fourth cell type, is gonna be the adrenal gland. 112 00:11:13,626 --> 00:11:16,502 The adrenal gland is here. 113 00:11:16,502 --> 00:11:25,337 It's called ad-renal because it's sitting on top of the kidney, which is the renal. 114 00:11:25,337 --> 00:11:30,928 This adrenal gland is also making a hormone, because it's a gland. 115 00:11:30,928 --> 00:11:34,081 That hormone is going to act right there. 116 00:11:34,081 --> 00:11:42,028 This is the little messenger and this is called aldosterone. 117 00:11:42,028 --> 00:11:51,367 So you've got aldosterone and ADH that are also acting on some of the same cells. 118 00:11:51,367 --> 00:11:57,397 I should rephrase that, not on the same cells, but on the same organs as the angiotensin II. 119 00:11:57,397 --> 00:12:03,137 So here aldosterone is gonna act on kidney cells to increase volume. 120 00:12:03,137 --> 00:12:07,802 ADH is gonna act on, like I said before, the kidney and smooth muscle. 121 00:12:07,802 --> 00:12:15,297 So let's scroll up and show you from the top some interesting things I want to point out. 122 00:12:15,297 --> 00:12:22,038 We've got at the very top, all the action, you remember, started in the kidneys. 123 00:12:22,038 --> 00:12:30,792 It started in the kidney with the macula densa cell and our JG cell and even our nerve endings were in the kidneys. 124 00:12:30,792 --> 00:12:36,560 One of the key target organs down here is of course the kidney. 125 00:12:36,560 --> 00:12:40,961 Things are starting in the kidney, but they're also ending in the kidney. 126 00:12:40,961 --> 00:12:44,196 Then you'll say 'Well what about the smooth muscle cells all over the body?' 127 00:12:44,196 --> 00:12:50,663 You're absolutely right it does also affects the smooth muscle in other parts of the body. 128 00:12:50,663 --> 00:12:53,924 I just want to point out the fact that the kidney is a major player in this game. 129 00:12:53,924 --> 00:12:55,891 That's one point. 130 00:12:55,891 --> 00:13:04,594 The other point is that when people talk about the RAAS-system, they're talking about certain pathways. 131 00:13:04,594 --> 00:13:09,961 They're specifically talking about, for example, this arrow right here, this hormone obviously. 132 00:13:09,961 --> 00:13:15,563 They're talking about this angiotensinogen and this angiotensin I. 133 00:13:15,563 --> 00:13:20,434 They're also referring to angiotensin II and all of its targets. 134 00:13:20,434 --> 00:13:27,226 They're gonna talk about angiotensin II affecting the smooth muscle and the two glands, 135 00:13:27,226 --> 00:13:32,760 the pituitary as well as the adrenal gland and its effect on the kidney. 136 00:13:32,760 --> 00:13:35,527 So they're really referring to all of those things. 137 00:13:35,527 --> 00:13:43,464 I want to make sure you remember that it's affecting four, at least four target cell types. 138 00:13:43,464 --> 00:13:50,828 Finally that aldosterone right here has a huge effect on the kidney as well. 139 00:13:50,828 --> 00:13:54,832 These are the important points to take away from this overview, 140 00:13:54,832 --> 00:14:01,233 that there are many different hormones involved, and I've tried to keep them color-coded all in orange, 141 00:14:01,233 --> 00:14:03,566 to make sure we keep track of them. 142 00:14:03,566 --> 00:14:07,566 And the fact that the kidney is a major player in blood pressure control.