- 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
See how Angiotensin 2 effects 4 target "organs" to increase blood pressure. Rishi is a pediatric infectious disease physician and works at Khan Academy. Created by Rishi Desai.
Want to join the conversation?
- 1:20he talks about increasing resistance. Resistance against what?(4 votes)
- Resistance against the flow of blood through the vessel. The smaller the diameter of the vessel (from vasoconstriction), the higher the resistance to blood being able to flow through that vessel.(21 votes)
- How does angiotensin 2 make the blood vessels vasoconstrict?(4 votes)
- All muscle constriction is due to an influx of calcium ions into the cell. Angiotensin II is a signal molecule that binds to certain proteins on the outside of a cell. This starts a chain of reactions that ultimately leads to calcium flowing into the cell, and muscle constriction.(11 votes)
- The greater the stroke volume, the greater the arterial pressure ->
deltaP = Q*R where the flow Q = "stroke volume" * "heart rate" .
But why does reabsorbed water mean increase in stroke volume?
To me it feels like reabsorbed water would mean larger blood volume. I can't see the connection between more reabsorbed water and a larger stroke volume.(7 votes)
- You had a great question.
If you have some water, any you add some more water, then you have more water than you what you started with. In the same way, reabsorbed water in your blood flow means that you have more blood now so yes, I congratulate you for noticing that point.
Larger volume of blood either means that your heart has to pump out more blood with each pump or, you have to increase your heart rate because you now have more blood that the heart needs to get through your body somehow. I guess the way our body does it is increase the stroke volume instead of the heart rate. :D(5 votes)
- where do the channels come from?(3 votes)
- ADH circulating in the blood binds to a specific receptor on the basolateral side of cells of the collecting duct. This initiates intracellular signaling (via a G-protein coupled receptor pathway) that up-regulates the fusion of vesicles that contain water channels (AQP2) to the apical cell membrane such that the water channels become part of the apical cell membrane.
- Thank you, great work. I have a doubt. Does ADH work also in the impermeable part of the Loop of Henle, the ascending limb, making it permeable to water? Or it works "only" in the Distal convoluted tubule and in Collecting Duct? Thanks so much! Barbara(4 votes)
- ADH works only in the distal convoluted tubule and in collecting ducts making it permeable to water by inserting aquaporins. This is to ensure that the solutes and sodium are reabsorbed into interstitial space creating osmotic gradient for water to follow by facilitated diffusion through the acquaporins.(3 votes)
- So if angiotensin II acts on kidney cells to result in an increase reabsorption of Na+ (therefore more being collected in the medulla and into the capillaries) then you would have again less Na+ reaching the macula densa cells resulting in an ongoing release of prostaglandin. Does this end up balancing out due to more volume passing through the kidneys or is this part of a forward feed system?(3 votes)
- When more Na+ is reabsorbed by the kidney tubules, more Na+ is retained and more water stays in the human body. As the blood volume increases due to water reabsorption, the blood pressure raises and this increase stimulates cardiac muscle cells in the atria of the heart to secrete atrial natriuretic peptide (ANP). ANP inhibits release of aldosterone by the adrenal cortex leading to less Na+ reabsorption and more water secretion in the form of salty urine.(2 votes)
- Is the ADH -> water reabsorption the reason why diuretics such as HCTZ are often prescribed to hypertensive patients?(2 votes)
- Thiazide diuretics were the first antihypertensive available for large scale use. Launched in the mid 50s, continue to be administered alone or in combination, to millions of hypertensive patients worldwide.
Thiazide derivatives such as hydrochlorothiazide and chlorthalidone, work primarily in the proximal part of the distal convoluted tubules, blocking the sodium-chloride cotransporter in the luminal membrane of the tubular cells. Under favorable conditions, these agents cause 5% to 10% of the glomerular filtrate to pass urine.
Thiazide diuretics have a vasodilatory action that is not yet fully elucidated, may also cause hyperglycemia. The initial drop in blood pressure results from a reduction in blood volume caused by diuresis, but the late phase is also related to an action on vascular smooth muscle.(4 votes)
- at6:15- I was under the impression that aldosterone not only reabsorbs na+ but also reabsorbs h2o but it only identifies aldosterone reabsoring na+(2 votes)
- By principal cells (see next video) reabsorbing sodium ions (Na+) from urine, water also enters the cell through osmosis. This can happen because the membrane of the principal cell is permeable to water, so water can move across it. Water does this because solute (here, Na+) concentration is higher in the cell after it allows Na+ to enter compared to outside the cell ,so water tries to make the concentration of Na+ equal on either side of the cell membrane. Hence, water also moves into the cell (ie is reabsorbed) when sodium is reabsorbed; movement of water into the cell decreasing Na+ concentration.
Osmosis is a type of diffusion (when a chemical species acts to achieve a balance or equilibrium for its' concentration ie speads out evenly) specifically for solvent (here, H2O) molecules moving across a selectively permeable (ie not everything can move across it) membrane to a region of higher solute (here, Na+) concentration.(3 votes)
- i was thinking that if the arterial pressure goes up, so does the venous pressure.
but according to this video, it seems like i was wrong.
why not much change in the venous pressure even if the arterial pressure goes up?(2 votes)
- arterial blood pressure is generated by the contraction (beating) of the left ventricle. Blood is forced through the arteries, into lower generations of vessels and finally into the capillaries. Blood pressure drops to nearly zero in the capillaries because of the increased overall volume; even though the vessels in capillaries are smaller, there are more of them. A totally different mechanism provides the force needed to return the blood to the right atrium - contraction of smooth muscle surrounding the veins. The veins also have one-way valves which prevent back flow of venous blood into the capillaries.(3 votes)
- at10:17you say that ADH works in areas that are NOT permeable to water (so we add aquaporins) and then you say that aldosterone works on cells that ARE permeable to water. This is confusing for me because it's my understanding that ADH and aldosterone are both working directly on principal cells of the collecting duct.
Maybe this is because aldosterone is only effecting water once there are aquaporins present from ADH but the way this is worded is potentially misleading.(2 votes)
- The Aldosteron works on cells that ARE permeable to water because it causes Sodium to be reabsorbed. When Sodium is reabsorbed, water gets back to the blood through osmosis- this is why those cells are premeable to water. In that case water can get back to the blood streem easily, through osmisis.(2 votes)
So we've talked about angiotensin 2, and we know that angiotensin 2 is a pretty small hormone. It's only about 8 amino acids. And so I'm going to draw it that way. It's 8 little balls representing 1 amino acid per tiny little ball-- almost like pearls on a necklace. And they're floating through this blood vessel, and they're headed to many different targets. So these little molecules are headed to various organs. And so let's talk about what those organs might be. So one target for sure is the blood vessel. So we have the blood vessel here. And in the blood vessel wall, we have smooth muscle. And the angiotensin hormone actually gets that smooth muscle to constrict. And so that's called vasoconstriction. It's actually easy to remember this because, if you think about the word "angiotensin," it's literally "angio" meaning blood vessel and "tensin" you can think of making "tense." So it's making the blood vessel tense and constrict down. We know that, if you cause vasoconstriction, you're going to actually increase resistance because that's how resistance works in tubes. And so if you're increasing resistance, try to keep in mind that formula that we talked about way back when for blood pressure-- delta P equals Q times R. And now we're finally kind of seeing how this formula is useful. If we talk about P on the arterial side minus P of the venous side. That would be the change in pressure. That would be delta P. And that equals Q. And this Q is actually going to be a couple things. It's going to stroke volume times heart rate. And so that's the flow. And all of that times resistance. I should make this very clear so you're not confused by what I'm writing here. Sometimes my penmanship gets a little bit wacky. This is your flow. So you have this increase in resistance. And you can see that, if I tell you that your venous pressure over here is really not going to change a whole heck of a lot and if you can increase your resistance, then you can definitely see how you would increase your arterial pressure. So it makes perfect sense using the formula. And you can see now how angiotensin 2 accomplishes that. Oh, and actually, the last thing I should mention before I move on is that this is actually a pretty rapid response. So very quickly the blood vessels will start constricting if angiotensin 2 is around. So now, another target organ would be the kidneys. And so here's a little kidney here, and this kidney is going to be affected by angiotensin 2 very slowly by comparison. So it's actually more of a slow response. And what actually happens is you get sodium reabsorption. As the kidneys are reabsorbing the sodium, they actually also pick up water. So as the blood starts filling up with more sodium and more water that you're not peeing out-- because you're, of course, reabsorbing it from what would otherwise have been urine. You end up having very concentrated urine, and your blood ends up getting all the salt and water. And your stroke volume goes up. So your stroke volume increases. And you can see from that equation that we just drew that if your stroke volume goes up, then again, your arterial blood pressure would go up as well. So here's a double check for that. So now, if stroke volume goes up, aneurysms go up. Your arterial pressure is definitely going to start going up. So angiotensin effects two different target organs. And actually, it's not even done there. It continues to affect other things. It even has an effect on the pituitary gland. So this is your pituitary gland. And the pituitary gland is actually in charge of releasing hormones of its own. When it gets a signal from angiotensin 2, it'll start sending off its own hormone called ADH. And ADH is antidiuretic hormone. It'll definitely cause vasoconstriction of the blood vessels, just like angiotensin 2 did. But instead of that sodium reabsorption, this ADH actually causes water reabsorption. Now, the effect for blood pressure in many ways is going to be similar. Because if you're reabsorbing water, again, your stroke volume will go up. And if your stroke volume goes up, your arterial pressure goes up. So at the end of the day, your pressure will still go up, but it's slightly different because it's water reabsorption versus salt reabsorption. And we'll talk about the difference momentarily. But before I get to that, the last target organ I want to mention is another gland called the adrenal gland. And the adrenal gland is literally sitting on top of the kidneys, and that's why it's called "ad-renal." And the adrenal gland is going to send off its own hormone called aldosterone. Aldosterone is going to affect the kidneys. And just like the angiotensin 2, aldosterone is going to cause salt reabsorption. And that's the main kind of thing that it does. And this salt reabsorption is going to lead to more water absorption and increase in stroke volume. So you can see how increase in resistance and increase in stroke volume is how our body is going to get our blood pressure back in control. Now I want to talk about one thing in a little bit more detail, which is this whole salt versus water reabsorption issue. So both of them increase stroke volumes. So you might be wondering what is the difference and why did I talk about the two separately. So let me get to that now. Let's do sodium, or salt, on this side. I'll write sodium. And on this side, I'll write water. And we'll talk about sodium first. So if you have your nephron here, this is what's going to eventually lead to urine. You have little cells here lining it, and you have them on both sides. I'm just going to focus on one side for simplicity. And you have a blood vessel. Let's say right here. And so these cells are going to help to reabsorb stuff that's otherwise going to go into the urine. One strategy for getting water back-- let's say you want to reabsorb water, which is what you want to do if you want to increase your blood pressure-- one strategy for getting water back would be to pull out salt. Because you know that if you pull out salt through osmosis, water is going to follow. So that's a pretty good strategy-- getting water back. That would work. But the assumption-- and this is very, very important-- the assumption is that this barrier right here is permeable to water. And so if it is permeable to water, then this sodium reabsorption strategy works. Now, let's imagine for a second that you try this, and it's actually not permeable to water. What would happen? Well, if you didn't have that permeability-- I'm going to redraw it over here-- then, when you try to bring the salt over-- and let's say you have your blood vessel again over here-- you try to bring your salt over. The moment that that water tries to follow, it's going to bounce off. It's going to do this and bounce right off. It's not going to work. You've got to try something different. That's exactly what happens is that, in areas where you don't have permeability to water-- so let's say this is not permeable to water-- you need a new strategy. And the strategy in a way is very, very simple. It's, well, if it's not permeable to water, why not forget about reabsorbing salt for the moment. Why not just do something like this and create little channels? So that's exactly what happens. You create these little channels, and water can just go through it. So basically, you make it permeable by creating channels. And you say, OK. Well, that's the better strategy for getting water in this case. So if it's initially not permeable to water, throw in a bunch of water channels and force that water-- or allow that water. Maybe force is not the right word-- allow that water to get through using your own channels. That's basically what the difference is. So if you look at ADH versus the other two hormones-- aldosterone and angiotensin 2-- ADH is using the water channel approach because here-- I'll write it in red-- here where this works the water is usually not permeable. I mean, the nephron is not permeable normally to water. And so that's why ADH throws in a bunch of water channels. And aldosterone and angiotensin work in areas of the nephron that are permeable to water. That's why their salt strategy works pretty well. But you can see now that, in both situations, the key is getting water back-- either doing it through a salt gradient or doing it through getting a bunch of water channels in there. In both situations, you increase your stroke volume.