- General overview of the RAAS system: Cells and hormones
- Renin production in the kidneys
- Activating angiotensin 2
- Angiotensin 2 raises blood pressure
- Aldosterone raises blood pressure and lowers potassium
- Aldosterone removes acid from the blood
- ADH secretion
- ADH effects on blood pressure
- Aldosterone and ADH
The juxtaglomerular apparatus plays a crucial role in blood pressure regulation. This complex structure consists of various cells including macula densa, endothelial, smooth muscle, juxtaglomerular, and mesangial cells. Understanding the triggers for renin release from this apparatus provides insight into how our bodies maintain blood pressure levels.
Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
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- @12:50"Para-" means near. What is the difference between a paracrine hormone and an endocrine hormone? Are they related?(20 votes)
- paracrine acts locally on neighboring cells while endocrine hormones can act on its target tissue from distance.(46 votes)
- so all this mechanisms purpose is to raise blood pressure
Are there mechanisms to lower it?(7 votes)
- My physiology teacher told us that there are not many natural body mechanisms to lower blood pressure. This is because high blood pressure problems are mostly a problem of the last 100 to 200 years for humans, because high blood pressure is caused by chronic stress and eating too much food. In other words, in terms of evolutionary history, humans have only been having high blood pressure problems for a very short about of time, so our body's have not developed a solution.(10 votes)
- My dr informed me today that my body is not producing the enzyme renin, or is not suppressed. Also, my aldosterone levels are 49. Im now researching this because i always have low potassium and low vitamin d levels. I always have a lot of stomach pain, diarrhea and or constipation. Lots if anxiety, and pain. What can i do? They want me to come back in august and eat 3 days of excessivre salt and then take a 24 hr urine sample to them in august. Should i worry about this? Because the other day i felt like my blood pressure was so high i ciuld onky lay down. Im really afraid of the blood pressure giving me a heart atack or stroke because i have been feeling pain for the last three days in and off in the middle if my chest.(3 votes)
- These are all questions and concerns that you should discuss directly with your physician. There is a lot of misinformation on the internet so be careful!(10 votes)
- If low sodium content in the blood causes renin release, which converts angiotensinogen into angiotensin I, and thus eventually causes an increase in blood pressure, why are high-sodium diets always associated with high blood pressure?(8 votes)
- In addition to the above answer, which answers your question about high-sodium diets, I don't think it is actually low sodium content in the blood that directly causes renin release, but low sodium content in the filtrate flowing through the nephron. This is what is sensed by the macula densa cells, which then sends the signal to the juxtaglomerular cells to release renin. Even with normal sodium levels in the blood, Rishi is saying that low BP would mean less flow at the glomerulus and therefore less sodium being filtered through.(6 votes)
- Regarding the 3rd trigger of renin release explained at11:16- low blood pressure leading to low Na in the filtrate (thereby stimulating the macula densa cells):
Presumably low Na in the blood would also lead to low Na in the filtrate even in the absence of low blood pressure - can hyponatraemia cause high blood pressure through this mechanism?(4 votes)
- unlikely, hyponatraemia is associated with low blood pressure because the salt attracts water, without the salt there will be low blood pressure, in the case of hyponatreamia, the body will try to return to homeostasis thus activating renin to increase BP, high blood pressure would unlikely occur because of the negative feedback of the increase Na in filtrate inactivating the macula densa cells(2 votes)
- Isn't there only 1 trigger because all the 3 triggers will only be set off in the same way? Sympathetic nerve cells sense stretch, trying to sense low amounts of stretch so they can fire to do something about it. Just like the sympathetic nerve endings fire when there is low blood pressure, the Macula Densa cells will only fire when the blood pressure is to low because of low blood pressure. Also, just like the other 2, low blood pressure is just naturally sensed by the JG cells.
Instead of "3 triggers", shouldn't it be "3 ways to notify the JG cell from 1 trigger (low blood pressure"?(3 votes)
- Another way to look at it (reflected in the video) is that one physiologic change (low blood pressure) activates three "triggers" that affect the JG cells. Sympathetic nerves affect other areas of the body as well as the JG cells so the triggers can have multiple effects. It is really just semantics because it all depends on where you draw the line for "trigger." You say the trigger is low blood pressure but what if the low blood pressure was due to sepsis. Then you have to keep stepping back and finding the proximate cause to identify a "trigger" when a reasonable person could see any step as being a trigger for the next step in the cascade(2 votes)
- At11:55when Rishi is explaining the low sodium trigger for renin release he states it is due to low blood pressure causing a low filtration rate in the glomerulus, and that this leads to low sodium levels filtering across the glomerulus. I had previously heard a slightly different theory, that the low blood pressure/filtration rate in the glomerulus meant a slower flow of filtrate through the proximal convoluted tubule/loop of henle etc allowing more time for the absorption of sodium/water into the medulla. This would obviously also lead to a lower sodium content in the filtrate at the distal convoluted tubule. Are both theories correct, or is one wrong?(3 votes)
- If you want to help memory juxta or iuxta also means close or near (to the glomerulus in the nephon in this case) in latin, because some guy decided to use latin and not the greek 'para' we use for every thing else. Thank you "guy", for making learning a bit more difficult(2 votes)
- My understanding is that the nephron filters proteins above a molecular weight (mw) of 67kDa (so the size of albumin or higher) but renin is only 37kDa and is secreted on the afferent side of the glomerulus. Even in its precursor form it is only 55kDa... How does it remain in the blood?(2 votes)
- I am not 100% of this answer but thinking logically, I would think renin is reabsorbed after being filtered into the filtrate. Because like other electrolytes, anything that the body deemed needed will be returned to blood (like glucose, Na, K, Cl, and others).(2 votes)
- At11:34, Rishi says that when the Macula Densa cells sense that there isn't enough sodium, because of low blood pressure then they send prostaglandin to ... and that raises blood pressure. But what if the low levels of sodium weren't from low blood pressure like maybe it's just because you didn't eat any salt/sodium that day. So would you have hypertension (abnormally high blood pressure) because you don't intake enough salt/sodium?(2 votes)
- Excellent question. The answer is "no", the low salt/sodium intake that day will not result in hypertension. If there is low salt in body tissues, then water will be secreted out in urine as water follows the salts (no salts, no water). Hypertension is usually due to too much water in the body.(2 votes)
Think back to the kidney, and we talked about how there's an efferent and afferent arteriole. This is the afferent arteriole going towards the glomerulus, and there's a whole clump of blood vessels here. And then there's the efferent arteriole that leaves that clump of blood vessels. And those blood vessels we know are going to be surrounded by the Bowman's capsule. And we named all the different parts of the nephron, the proximal convoluted tubule, the loop of Henley, and then this is the distal convoluted tubule. And I'm drawing it in between the afferent and efferent arteriole on purpose, and this is where all the different distal convoluted tubules meet up into that collecting duct. And in this video, I want to basically expand on this little piece, where the efferent and afferent arteriole are coming together into the glomerulus and, in between them, how there's that distal convoluted tubule. So just keep that picture in mind as I start expanding this drawing. So over here, let's start with the afferent arteriole. I'm going to start drawing it, hopefully I'll have enough space here, something like that. And these are the endothelial cells here that are lining that blood vessel, that arteriole. And on this side, we have the same endothelial cells, of course. But now it's leaving the glomerulus. So we've got coming and going. And over here, this is the efferent arteriole. And, of course, the other one would be the afferent arteriole. And in fact, I'm going to reverse this arrow just so there's no confusion about direction of blood flow. I don't want you to be confused about where the blood is flowing. It's going to be going like that, and this is the afferent arteriole. So I've got my blood vessels labeled. And between the two, I also have the distal convoluted tubule, so let's draw that in. And this is the cells surrounding that distal convoluted tubule. There it is. And there's some very special cells also in here, and I'm going to draw in a different color. And they are the macula densa cells. It's actually part of the tubule, but they're very special. So I'm going to draw them for that reason. So this is the distal convoluted tubule. And in green, I said the macula densa cells. A lot of names I'm throwing at you. And I want you to start feeling comfortable with these names, because they're actually going to be used quite a bit. Macula densa cells. 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 up at you. Now, the next thing I want you to think back about and remember is that arterioles don't have just one layer. I mean we know that arterioles have multiple layers. The inner layer, the tunica intima, is the endothelial cells, we know that. But there's also smooth muscle cells. We know that there's also a layer called the tunica media that's in here with smooth muscle cells, and I'm going to try to draw some smooth muscle cells right there. So we have a layer of these smooth muscle cells. And if you look closely under a microscope, you'll see that there's also some interesting cells right here. And I'm drawing them in blue just to highlight that they're different, but they are actually very similar to smooth muscle cells. And so in a way, they're specialized smooth muscle cells. So let me label these two new cell types I've drawn for you. Actually, I'll label them down here. Smooth muscle cells. And they're on the afferent arteriole side. You'll see them a little bit on the efferent arteriole side as well, but mostly on the afferent arteriole side. Smooth muscles cells, and then you have these juxtaglomerular cells. Talk about a funny word, huh, juxtaglomerular cells. So juxtaglomerular cells are there. And if you looked under a microscope, they'd be full of granules. And so sometimes actually they're even called granular cells. And so let me draw in some granules just to remind you that that's what people see under a microscope, little green granules in this case. And I'll put them into all of them. And you know that these cells are on both sides of the vessel because, of course, we cut it long ways. So we're just looking at it as if it's disconnected. But you know these two sides are obviously touching if you thought of it in three dimensions. And now I've talked about four cell types. Let's round it out with the last cell type. This is in orange now. This is the mesangial cell, and mesangial cells are really there for structure. They're really there to hold the whole thing together so that the blood vessels and the nephron are in close contact and structurally sound, so think of them as being there for support reasons. So these are the mesangial cells. And so combined, if you think about all this stuff together-- remember, this is all the white box in the little picture kind of blown up. If you think about all this stuff together, the macula densa cells-- we've got the endothelial cells, the smooth muscle cells, the juxtaglomerular cells, and the mesangial cells. Put together, this whole thing is the juxtaglomerular apparatus. Kind of a funny word, but it's how people refer to all these cells. So juxtaglomerular apparatus. And the key here is remembering that the goal of the juxtaglomerular apparatus is to release renin, and so think about where renin is. Now, I mentioned these granules right here. And these are actually each going to be loaded with renin. So these little granules, when they dump themselves into a blood vessel, this is your renin. And that renin is going to make its way into the afferent arteriole, just the way I drew it. And then it's going to go through the glomerulus. And on the other side, it's going to sprinkle out and go out the efferent arteriole. So that's the way renin gets released. But what we haven't figured out yet, what I haven't said, is how. Why does the juxtaglomerular cells, why would it release or how does it release the renin? What is the trigger? So let's talk about triggers now. Let's figure out what are the key triggers for release of renin. And there are three actually, the three common ones are what we now. So one is simply low blood pressure. So these cells are going to fell-- mechanically, they're going to feel less blood pressure. They're going to say, well, what's going on here? Pressure is low. We've got to do something about it. Great. We're going to release renin. So one trigger would be low blood pressure. That's the first one. And that's actually directly sensed by the juxtaglomerular cells, so that's actually sensed right here. I'm going to draw a one for that. Now, the second trigger is a nerve cell trigger. And I actually haven't even drawn that in for you yet. So remember that this is kind of a blood vessel here with our two layers, our endothelial layer, and then we have our tunica media layer. And there's also an external layer, tunica externa. And we also have our blood vessel here. These mesangial cells are also kind of specialized smooth muscle cells. So we have these layers of blood vessels, and the two blood vessels here are kind of merging and fusing right here. They're kind of coming together right here. But in this external layer, you actually have-- I'm going to draw in yellow-- little nerve endings. And remember, nerves can end in that layer, that tunica externa layer. And so you have these sympathetic nerve endings. And they actually come and sit with their little endings right on the juxtaglomerular cells. So they're sitting right there. And when they fire, that's going to make the juxtaglomerular cells want to dump out their renin. So the second trigger is sympathetic nerves. Now, there's one more trigger, third trigger. And this one is actually a little bit of a distance away, and it's the macula densa cells. So I mentioned them earlier. And I said that they're special, and I haven't really gotten into why they're so special. So let me tell you right now. So what happens is, these macula densa cells, they're sitting there in the distal convoluted tubule kind of sampling what comes through. They're just kind of feeling out what comes through. And they're seeing sodium come through, and they're checking and checking. And they're saying, OK, is there a lot of sodium? Or is it a little bit of sodium? And when they start sensing that the sodium content, that the amount of sodium coming through that distal convoluted tubule is really quite low, when they start feeling like not too much sodium is coming through, they start thinking to themselves, why is this happening. And if you think about it, you can figure it out, too. So if there's not a lot of sodium here, that's probably because there's not a lot of sodium here. And that could be because there's not enough sodium here or here. So really, when the distal convoluted tubule senses low sodium, it's probably related to the fact that not enough sodium is getting in at the get-go, at the point of filtration. And that could be a reflection on low blood pressure. So the macula densa cells, when they sense low sodium levels, really what they are sensing is low pressure in that glomerulus. And so if there's low pressure in that glomerulus-- remember, this is our glomerulus right here. If there's low pressure in the glomerulus they think, OK, well, that's probably the reason our sodium levels are low. And let's send a signal out to the juxtaglomerular cells. So low sodium picked up by the macula densa, it means that the filtration pressure in the glomerulus was too low. And so what they decide to do is-- let me find a new color here. Maybe something like this-- is they send a little messenger-- I'll do my messenger in orange-- to go over to the juxtaglomerular cells. And that messenger is a little molecule called prostaglandin. And it's a local messenger, meaning that it really doesn't act far, far away from these two cells. It just acts locally. So this local hormone, sometimes called a paracrine hormone-- I'll write that here-- is going to send the signal from the macula densa cells over to the juxtaglomerular cells to say, hey, here's a trigger. We sensed low sodium, and we think it's because the pressure is too low. Why don't you go and do something about it? So those are the three triggers. And actually, I don't think I have been good about labeling them. This is trigger number two, and this is trigger number three. These are the three triggers that will make the renin get released into the bloodstream. So this is a picture of renin. Here's a picture of the molecule, and I've actually already drawn kind of a Pac-Man like shape around it. But when I talked about renin coming out of the juxtaglomerular cells, I just want you to get a sense for what it actually looks like. And this is a 3-dimensional figure of this protein. Keep in mind this is a protein hormone, meaning it's a protein that has the ability of letting one cell talk to other cells kind of at a distance away. So this is what that renin looks like, and we'll discuss more about how renin works in the next video.