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Physiology, Lecture 8# Renal System

First lecture for 2nd exam18-10-2010Dr. Nayef Gharaibeh

RENAL SYSTEMWhen we are talking about renal system, we should cover the following

objectives.First, we will introduce you to physiological anatomy of kidney and the functional unit of it (which is the nephron). Second, we will talk about the function of this system. Third, we will start talking about the first step of urine formation. Because when we form our urine, it goes through many steps. First, filtration. 2nd, reabsorbtion. 3rd, secretion and finally the excretion. So these are the objectives of the lectures in renal system.

When we are talking about renal system, we are talking about two kidneys. Each can weight about 150g, and they’re located on the back of our abdominal cavity. And when we talk about the importance of the system we mentioned that our kidneys. We have two of them; one is more than enough to provide us with normal physiological function. That’s why when we have one defected kidney, we can take it off out, and the patient will live normally, the rest of his life. But the problem will be that he will have only one kidney, if something wrong, that will be dangerous for his life. But one kidney is efficient to form the normal urine and to do the proper function of the renal system.

What are the functions of renal system (?). There are about 5 or 6 functions, or even more. The most important function of renal system: to excrete metabolic waste. This is a major function. In our metabolism, normally we utilize the good thing for our life, but there are some products produced which are not good for health. So we should get rid of them. The way to get rid of this metabolic waste is the renal system. But it is well known, it is not easy to get rid of metabolic wastes in solid form. They should be dissolved or suspended. So in order to do so, we have to have some water with that urine.

So this is the major function but there are other functions which are also important. Renal system maintains stable extracellular fluid. Between practice

extracellular fluid is the internal environment. When the renal system stabilizes that, we stabilize the homeostasis. What do we mean by stabilizing the extracellular fluid? We mean by that, it make the extracellular fluid volume constant and the composition constant. So it will regulate the volume of body fluids and it will regulate the content of the body fluids.

Third function, it plays a big role and major one in acid base balance. You’ve heard this acid base balance. Acid base balance: where the pH level is important for our live, we don’t want to change the pH. So it should be 7.4 but it’s impossible to keep it fixed all the time. There is a variability from up and down, depend on the ingestion, whatever getting inside our body, what’s the level of gases in the internal environment, especially the carbon dioxide. As we mentioned in respiratory system, if there is an increase of CO2 in your body, you will hyperventilate, in order to get rid of that CO2. Because it is toxic and plus, because it changes the pH. We don’t want to change the pH.

So acid base balance, there are three major system playing one function, to keep the pH constant. Those systems are: 1. the blood 2. Respiratory system 3. Renal systemWhy we have three systems to stabilize pH? Because it’s very important. Now, pH is dangerous to be changed to acidic or alkaline. If there is any change of pH within seconds, the blood will interfere. The protein of the plasma protein, they will interfere to stabilize the pH. So the function of blood, according to the pH or acid base balance is very fast. They will interfere within seconds. Now, if for reasons, the blood itself was not enough to stabilize pH, and then pH will be different than normal. In this case, the second system will come, which is the respiratory system. Now after few seconds, if your pH is still abnormal, the respiratory system will interfere, by hyperventilating or hypo ventilating.

If it’s acidic inside our body, we will start to hyperventilate, to get rid of CO2. If its alkaline, we’ll start to hypo ventilate, to increase the level of CO2, to get back to normal pH. This is within minutes. Now, if for a reason, the pH didn’t go to normal after respiratory interference, then the renal system will come. It will come, after hours and days, but it will correct the pH for sure. Then in other words, the most efficient system for acid base balance is the renal system. It takes longer time, but it is very accurate. If the pH change, it will get it back exactly to 7.4. So, it is efficient by returning to the normal pH. But regarding the time, it is late. It doesn’t matter. The most important is to get the pH normal. This is another function of the renal system.

Also we know from the blood lectures that kidneys, they secretes erythropoietin which is the stimulus for erythropoiesis. So it’s another function for the kidneys. Also I think we mentioned rennin secretion somewhere in our lecture, or we will repeat that in detail in renal system. This is another function of the renal system. They stabilize blood pressure in the vascular system. Since they keep the body fluid constant in volume, they can stabilize the blood pressure. Also, they can conserve or deplete the extra sodium or the extra salt, by depleting the extra salt or keeping the normal salts inside your body. They will stabilize the blood pressure again.

And also they have a function to change, or to stimulate, or to activate Vitamin D. Vitamin D is important in metabolism, but it is in inactive form inside our body. Kidneys, they are able to modify that vitamin, to be active one and to be utilized.

Now, we are talking about a kidney, you saw how it looks. If you look again, to that picture, you will see that the peripheral part of the kidney is not brown but a little bit light of brown. This part is called cortex. The cortex of the kidney, but in the central you will see very brownish colour which is the medulla (Medullary part). Why it is important to know this, because when we are talking about the functional unit of the renal system, which is called nephron, we have two types of nephron. One group, about 80% of them is called cortical nephrons, and the other group is called juxtamedullary nephron. And there are big difference in the structure and the function of those two groups.

From the kidney, there is special collecting chambers, called the pelvis (where the urine will be collected there) then, it will leave the kidney, to the ureter. Ureter is a tube, coming from the kidney down to the urinary bladder. Urinary bladder, the storage chamber of the urine, then from the urinary bladder we have the urethra, which is different from male and female, but the function of urethra to get out the urine by voluntary and involuntary mechanism of physiology for urination.

Now when we are talking about the functional unit, we mention that it is called nephron. If you look to this picture, this is a nephron, and this is another nephron. Nephron has two parts, the glomerulus (the beginning of the nephron) and the tubular part. System of tubules, they are different in shape, location and length. So if you take the first nephron, the one I’ve showed here, this is the 80% of the nephrons in the kidney and the number of nephrons in each kidney is about 1 million. In other textbook you might see 1.5 million but the average is 2 to 3 millions in both kidneys. So in this huge number, we have 80% of them, they look like this one (which is the small). This is the glomerulus and then this is the tubular system. Tubular system, it starts with the structure called Bowman’s capsule. It’s a one layer epithelial structure tubule, start with bowmen’s capsule then, after Bowmen’s capsule comes the second structure of the tubular system, it is called proximal tubule. 3rd one, the U shape structure, it is loop of henle. 4th, this one is the distal tubule, then collecting tubule. And finally, we have this long structure of duct. It is called collecting duct.

This is the nephron. The glomerulus, and the tubular system. Now, the one I followed in the picture is the cortical one. Let’s go through the other one, juxtamedullary nephron. This is the glomerulus inside the Bowman’s capsule.

Bowman’s capsule, again, proximal tubule, loop of henle, distal tubule, collecting tubule, and collecting duct.

Now what’s the different between cortical and juxtamedullary nephron. First, most of the nephron (structurally) of the cortical type, located in the cortex. The only part located in the medulla is the small part of loop of henle and the collecting duct. Collecting duct of all nephrons, they start in the cortex and then they go deep in the medulla. Now let’s go to the juxtamedullary nephrons. And if you look to the glomerulus and the proximal tubule (in cortical nephron), they are far away from the medulla. They are on the top of the cortex whereas the juxtamedullary nephron, the glomerulus and the proximal tubule, they are in the cortex but on the border of medulla. Then, the loop of henle, it goes deep in the medulla (yous see the loop of henle of the first type? Very small amount of it touches the medulla). In the juxtamedullary nephron, most of the loop of henle and part of the distal tubule are located in the medulla. Then, the late distal tubule and the collecting tubule, they go back to the cortex and they will join the collecting duct. And the collecting duct goes down to the pelvis of the kidney.

It is so important to remember the location for the function of these parts of tubular system. When we discuss later how we form the urine, you will realise what’s the function of the cortical nephrons and juxtamedullary nephrons. And since the tubular system is just one layer of epithelial cell, structurally it’s almost the same, but since we name it proximal, loop of henle, distal, we gave different names because they have different functions in the renal system.

Now, loop of henle, this one and this one. It has ascending limb and descending limb. Ascending limb; which goes down. Then up; the descending limb. Now this structure the U shape, also without that structure, the renal system will be vanished. So this U shape is so important to make this nephron perform the normal function; which is the urine formation.

Let’s take the first part of the nephron, which is the glomerulus. It’s a structure of vascular system.

It’s just vessels but it differs than the capillary network (you remember the body fluid exchange in the capillaries), you remember how plasma leaves the first half of the capillary? Then it goes back to the 2nd half of the capillary. In the renal system, it has different structure. You remember that artery, arterioles, capillary, venules, veins; this is the normal structure of vascular system.

In the kidneys, it’s completely different because the function is different. Here, the blood circulation is not to feed the kidney. Why is the blood circulation inside the kidney?To clean the plasma from metabolic waste and extra amount of different substances. In order to achieve that, we have different blood circulation and the blood circulation of this system is as follow: We start with the blood flow inside the kidney. (slide no 7)This is arteriole. Then, we will have this structure. It is called afferent arteriole. After afferent arteriole, we have a net of capillaries. It is called glomerular capillaries. Now remember, if we are in the systemic circulation, after capillary we will have the venules. But here, when we finish with these capillaries, look how many there are inside the Bowman’s capsule (figure at slide no 11, textbook page 410).

We go out of the glomerulus by efferent arteriole. We have the same arterial structure, but it is efferent arteriole. Then, we will go down and we will form another capillary set. This one which is called peritubular capillaries set. Around the tubules, we have another set of capillaries. After the peritubular capillaries, we will have the blue structure of venules which goes out by veins. Now, to make it important, I have to repeat it. We have renal artery it goes from the aorta to the right kidney one, to the left kidney the other artery. It goes inside the kidney; it will be divided to different small arteries. Until they reach million of glomerulus inside the kidney. From there, they will send million afferent arterioles, to reach other one arteriole. From that arteriole, we will have a net structure, network of capillaries. All of that structure called glomerular capillaries. Then when we finish the network of capillaries, it will go out from the glomerulus by efferent arterioles. When it goes out, it now will go to the tubular system. Finish from the glomeruluar to the tubules. It doesn’t matter, cortical or juxtamedullary; they will cause another set of capillaries around tubules and it is called peritubular capillaries.

Now, there is one difference. If we are talking about juxtamedullary nephron, these peritubular capillaries they will form a new structure called

vasa recta. It is important, since there is special name for that structure, it has special function.

Now, if we go back to the glomerular capillaries; the first structure of capillaries, if we measure the hydrostatic pressure in there, if you still remember, what’s the hydrostatic pressure in the systemic capillary for the body fluid exchange? It was 30 mmHg in the first half and 10 mmHg in the 2nd half. In this glomerular capillary set, it’s completely different. It is one hydrostatic pressure in the beginning and the end. And it is about 55 mmHg(in your textbook). Now there is a different between this capillary set and the systemic. It has more hydrostatic pressure. Why it has more hydrostatic pressure? And why it is the same from the beginning until the end? Because we have the afferent arteriole with the smooth muscle control and efferent arteriole with the smooth muscle confront. Most of the time, we have a dilatation of the afferent and constriction of efferent. Which allow the blood to go very high inside the glomerulus, but doesn’t go out easily. So the hydrostatic pressure is 55 mmHg.

Another thing, in the glomerular set, there is plasma proteins, similar to the systemic circulation. But if you measure the osmotic pressure of these plasma proteins in the glomerular capillaries you will find it is not 28 mmHg as capillaries. It is 30 mmHg. So it is more. Why it is more? Even we know that the plasma protein concentration is normal, whether it’s in the kidney or in the capillaries. It is more because in this place ( in the glomerulus) we have a huge amount of water filtration. It goes down to the tubules. When we lose the water, we increase the concentration. That’s common sense. So the oncotic pressure of the plasma protein in the glomerulus is 55 mmHg.

The 3rd difference between the capillaries in the systemic circulation and the capillaries of the glomerulus is the permeability. If you study the structure of the capillaries in the glomerulus, in some text book they say it’s 500 times more permeable than systemic circulation. Other book, they mention about 200 times. The idea is; they are more permeable than the systemic circulations. So their structure, in a way, helps to get rid of the plasma easily when they flow inside the glomerulus.

Now, this is the schematic structure of the nephron. Another important fact is if you take one nephron alone, with the blood circulation, it will continue forming urine as a normal kidney. So the function of the kidney is the some of the product of each nephron. So in other words; nephron works independently. Now this structure of nephron, this is the glomerulus, the

capillaries inside, afferent, efferent, then Bowman’s capsule, proximal tubule. Start with loop of henle, down then the descending end of loop of henle, then the distal tubule, look at the distal tubule. It goes back to the cortex, but it will go between afferent and efferent arteriole. Distal tubule of each nephron, when it goes back through the cortex, it will go through the afferent and the efferent arterioles. So afferent and efferent arterioles are like hugging the distal tubule. This structure of touching, it will form special apparatus, which is here a little bit dash green line, this part of the nephron is called juxtaglomerular apparatus. I don’t know why in your textbook they didn’t expain it in detail but it’s important. Juxtaglomerular apparatus.

Now, since we finished with the physiological anatomy of the nephrone, we will start talking about the function of each nephron. First function of the renal system is filtration of plasma. We want to filter the plasma. Where? In the glomerulus. To where? To the Bowman’s capsule. So the plasma should leave the vascular system; which is a part of them, from this glomerular capillary to go out, in order to reach the tubular system. If it wants to do so, the plasma should cross the epithelial cell of the glomerular capillaries. Then it will cross the basement membrane between the capillaries and tubular system. After that, it should cross the epithethileal cells of the Bowman’s capsule. Then it will go down to the Bowman’s capsule inside the tubule.

So this is the glomerular membrane trough which the blood plasma should cross. And it’s easy to cross it because we said the capillaries very permeable and also, the epithelial cells of the Bowman’s capsule; they have slids like the podocyte cells. Between them, there are a lot of spaces through which the plasma can cross.

This is the capillary. Here is the plasma. You see these small holes or pores, these are capillary pore. There are millions. So, it’s easy for the plasma to go through them. But when they (plasma) go through them, they will face this whitish colour basement membrane. And there are some structure of special proteins which help the plasma to go through it.

After that, these brownish are the epithelial cell of the Bowman’s capsule. In between, there is no tight junction as you see. It is open channels. So the plasma should go through from here (capillary) to here (Bowman’s capsule) and it is easy. And if you look to this structure, this is the plasma coming in, should cross the membrane, to the tubular system. Now, in order to cross that and we mentioned the name of that filtration. It’s not diffusion. It’s the same as the filtration of capillaries in the body fluid. But the mechanism is different. Why different? Because if you look back to the forces in here, you will have the hydrostatic pressure inside capillary and we said its 55mmHg, you will have the oncotic plasma protein osmotic pressure inside the capillary which is 30mmHg and inside Bowman’s capsule; because it is a capsule, it is full of fluid. This filling fluid will create a hydrostatic pressure. The hydrostatic pressure inside the Bowman’s capsule equal to 15mmHg.

Now, just to illustrate how the permeability in the glomerular capillaries, look to this.

This is the way; the plasma will leave the capillary, to the Bowman’s capsule. Inside the glomerulus, we have 55mmHg of hydroststatic pressure of plasma. This hydrostatic pressure pushes the plasma out. Because it’s in the gross compartment with 55mmHg, so it will push the plasma out, by a force equal to 55mmHg.

We have millions of pores, so the plasma will go down. Now, the oncotic pressure, it is 30mmHg here. Remember, the plasma protein will not leave the glomerulus. These pores, even there are millions, but they are not large enough to let the

protein out, with normal condition. Because they are inside the capillary, they will create osmosis. So they will not allow the plasma to go out. They will start to do suction for the plasma. So the direction of this force is opposing the direction of hydrostatic pressure. It’s the same discussion before in the capillaries. So it should be like a piece of cake to understand.

Now we have 55mmHg pushing the plasma to the tubular system. We have against it 30mmHg. With the plasma goes inside the Bowman’s capsule, and there is fluid inside the capsule, this fluid inside the capsule create a hydrostatic pressure equal to 15mmHg. So it doesn’t allow the plasma to get easily inside the capsule. If I have an empty capsule, it will be easy to get through it with water, but if I have a fluid capsule, it will not be easy. I have to overcome the hydrostatic pressure created inside the capsule.

So we have 30mmHg against, 15mmHg against, and 55mmHg with the plasma filtration. The net filtration pressure is equal to 10mmHg. This is the normal net filtration pressure in the nephron, in the kidneys. Now, since we have 10mmHg and we have good permeability, a huge number of holes, and pores and filters in the podocytes, of the Bowman’s capsule, the plasma will leave the capillaries to the Bowman’s capsule. How much? Equivalent to the

10mmHg. What’s the equivalent of that? If you measure, the amount of plasma leaving the capillaries, in the glomerulus, to the Bowman’s capsule each minute, you will get this number; 125ml of plasma each minute. Listen to that number carefully.

You are sitting now, all of you, in your kidneys, each minute, whether you’re drinking water or you don’t. Each minute, there is 125 ml of plasma leaving the glomerulus to the Bowman’s capsule. Let’s calculate in each hour. Times 125 ml with 60. This will be how many ml per hour. Let’s calculate that because during sleeping, your kidneys are functioning. They don’t stop. Let’s calculate how many ml you will filter a day. This number will be 180L of plasma filtered in your nephrons each day. Let’s go back to our knowledge. What’s the volume of plasma? What’s the real volume of blood? 5 to 6L. Let’s say 5L. the plasma is 45% of it so about 2.5L+. It is about 3L of plasma. Now every day, 180L of plasma will be filtered. So how many times, the plasma will be filtered? It is about 65 times. Why I mentioned that (?) It’s because I want you to imagine even our kidneys are small as our hand, two of them. But they are efficient to clean our plasma 65 times per day. Like a washing machine. The more you wash thing, the more they’ll be clean. They are not able to take it at once, and clean it and take it back. They do it gradually, but they do it efficient because they do it 65 times per day. This is the efficiency of the kidney to clean plasma but imagine; if we lose our plasma 65 times a day, what happens to our vascular system?

In this case, god gave us another function to the renal system. Not only the filtration. Filtration is the first step. The 2nd step is reabsorbtion. We filter 180L per day and we get back, 178.5L per day. So what’s that remains are the 1.5 litre which is the urine output. Every day, under normal condition, we lose only 1.5L of urine. But we clean, 180L of plasma portion by portion from the total volume of plasma which is 3L. Now we start to imagine the efficiency of the renal system.

Now, the amount of plasma filtered in the glomerulus per minute is called Glomerular Filtration Rate (GFR). And it is 125ml per minute. If for any reason, we need more filtration, there is a mechanism to do so. If there is any situation we want to decrease the GFR, there is a mechanism to do so. How’s that (?) It’s so simple. You remember the glomerulus, you remember the afferent arteriole and efferent arteriole. We said that afferent is dilated, efferent is constricted. By doing so, we will have 55 mmHg hydrostatic pressure of the glomerular capillary.

Now, if we want to decrease the GFR, we want to save the plasma. So what happened, the afferent arteriole will be constricted, efferent arteriole will be dilated. By doing so, you will decrease the blood flow inside the glomerulus. By decreasing the blood flow inside the glomerulus, you will decrease the hydrostatic pressure. And you will let the blood outside the glomerulus easier because there is a dilatation of efferent arteriole. Because of that, you will not have 55mmHg of hydrostatic pressure, but maybe 50, 52 @ 53. But when we have such hydrostatic pressure, the oncotic pressure is still the same; the Bowman’s capsule’s pressure is still the same, so the net filtration pressure will not be 10mmHg. It will be less. Instead of 55 – 45, we will have 53 – 45. So it is about 8 or 7mmHg. By decreasing the net filtration pressure, the GFR, the rate of filtration will be less and thus you decrease the GFR.

The

opposite is possible. If we want to increase the GFR, we want to increase the loss of plasma. In this case, we will have more dilatation of the afferent arteriole and more constriction of the efferent arteriole. By doing so, you will increase the blood flow inside the glomerulus and you will decrease the outflow of blood, so you will increase the hydrostatic pressure inside the glomerulus. Instead of 55mmHg, you might have 56 or 57 or 58. The oncotic is still the same, capsular still the same, so the net filtration pressure will be more than 10mmHg and that will increase the filtration rate in the glomerulus. This mechanism is controlled by sympathetic nervous system and other system like Juxtaglomerular apparatus. These are the mechanism where you vasoconstrict the efferent arteriole, where you dilate the afferent. And you should remember when we are talking

about the sympathetic nervous system, the efficiency for dilatation or constriction for the afferent arteriole is more than the efferent arteriole. So the level by which they affect the constriction or dilatation mainly to the afferent arteriole, not the efferent. And this is important.

Now, this is another system where it summarizes what’s the homeostatic function in our body, if the arterial blood pressure is decreased, if the blood pressure is below normal; what the system does? What the human body does in order to return back to the normal blood pressure. First of all, when you decrease the blood pressure, there are special receptors to sense that. There are in the aorta and the carotid sinuses. It is similar to those in the respiratory body. You remember the peripheral chemical control, it is similar, but they sense the low blood pressure. Those they sense the very low oxygen, below 60, they slightly (they sense) carbon dioxide.

Let’s talk about this thing. Now, when they sense the low blood pressure, they will stimulate sympathetic nervous system. Activation of this system, it will go in this direction in short term (not in long term). This one, and this one. This will cause an increase in cardiac output, more pumping of the heart. It will increase the blood volume coming out, and that will increase the blood pressure. Also at the same time, when the sympathetic nervous system is activated;

this cause total peripheral resistance, spasm of arterioles. And you should know, when you do a spasm, you’ll increase the blood pressure. And that will change the arterial blood pressure towards normal. This is in short term.

In long term, when we have a spasm of arterioles, the most important one in the kidney is the afferent one. Efferent is not important for sympathetic nervous system, as I mentioned. So in the afferent, it will cause vasoconstriction. Vasoconstriction will decrease the glomerular capillary blood

pressure, the hydrostatic pressure; the 55mmHg will go down. That will cause a decrease in GFR. Decease in GFR will decrease the urine output. Instead of losing 1.5L of urine, you might lose half litre of urine. So you saved one litre of plasma. This one litre will go back to the plasma and it will increase the blood volume and finally it will adjust the blood pressure in your system.

Now, the cardiac output. Normally our heart pumps bloos ouside to the whole body. The amount of blood pumping per minute is equal to almost 7 litres. 6L, 7 or 5, different in males and females. This 6L of blood each minute goes to different direction. Portion of that 6L will go to the brain, another portion to the liver, 3rd portion to the intestine, 4th to the muscle, 5th to the skin, and portion of that, it will go to the kidneys. Now, if you go back to the systems I’ve mentioned, and I ask you, which system will take the most blood (?) It’s easy to answer. The gastrointestinal system (GI) is the winner. They will take a huge amount of blood under normal condition. But if the person is exercising, the muscles will take a huge amount from the 6L (blood). This kind of distribution is because of physiology. We want to get more blood to the area mostly needed.

Now the brain will take a fixed amount of blood, no matter what happen to our physiological body. Brain always takes the exact amount of blood needed for this important system (nervous system). Now if you go to the skin, they don’t take too much blood because it’s not needed. Now let’s take the kidney; small 150g to the right and 150g to the left. A total of 300g, they don’t need much blood at all. But if you measure the amount of blood going there, it is almost ¼ of the cardiac output. Why? The answer is there. They don’t need the blood to be feeded, they need the blood to clean it for us. So ¼ of the blood will go to the kidneys for cleaning, not for feeding. And this ¼ or 1/5 th; 22 to 25%, it is about 1140ml of blood per minute. Now that blood is blood cells and plasma. Here, they consider the hematocrytes is 45, so 45% is blood cells and 55% is plasma. If you want to calculate how many ml if plasma getting inside the kidney, you have to take this number (1140ml) times 55%. You’ll get about 625 ml of plasma each minute, getting inside our kidney.

Few minute ago, I told you each minute, we filter in the glomerulus 125ml of filtrate. So how much plasma will be filtered? It is about 25%. So ¼ of

the plasma will be filtered. Ok, huge amount of the plasma will be filtered. Now what’s the remaining, the blood plasma which is not filtered, where did they go? Now, we have.. let’s take 100ml of plasma just to make it understandable. 100ml of plasma will go through the afferent arteriole to the glomerular capillary; 25ml of them will be filtered at the Bowman’s capsule. The remaining 75ml will go out through the efferent arteriole, and they will follow the peritubular capillaries. So they will go back, around the tubules but in other area, not in the glomerulus.And this part will be our talk in the next lecture.

Sorry for any mistakesAll the best!

Done by; Farah Hanisah