Reabsorption

Some pointers of the previous lecture: Renal system. Physiological anatomy of the kidney. We have 2 kidneys 150 g each. Each kidney contains 2 million of nephron. *the process of urine formation contains: 1. Filtration. 2. Reabsorption. 3. Secretion. - Filtration is huge its about 180 L/ days , but its random It moves a plasma from a capillary to the Bowmans capsule without proteins.

Reabsorption
The re-absorption in the renal system is our topic for todays lecture. - its huge but selective . - we have 125 ml/min filtration against 124 ml/min of reabsorption, so by the end of the day we will have 1 mL/min formation. Things that we supposedly- already know: * We should remember that the glomerulus (the exchange that occurs) its 500 times more permeable than systemic circulation (the classic blood circulation of the body). The 100 time of it is related to the vascular structure of the glomerulus while the extra 400 is related to the visceral layer (basement membrane) and the epithelial structure of Bowmans capsule. * you know that hydrostatic pressure is the major force in the capillary. But it cant be controlled by the constriction and dilation of afferent and efferent arteriole.

Hydrostatic pressure effect on the GFR

if we have a decrease in blood pressure .. that will cause a decrease in hydrostatic pressure in the glomerular capillary , which mean less net filtration pressure .. which means a decrease in the GFR. so we will not have 125 ml/min , we will have below that (and this is wrong and shouldnt happen) and if that happened there is a different control system .. composed of Stenosis and

Dilatation of the arteriole .. but these arent the major control systems. The major one is related to another structure that is called Juxtaglomerul Apparatus.

Structure of The Nephron

* The segments of the tubular system : (the renal corpuscles , proximal tubule , loop of Henle , distal tubule and the collecting duct). *each nephron is the same. The 2 million nephrons have the same structure. * in the histological structure of the tubular system we can see the distal tubule, afferent and afferent arteriole , and the glomerulus. * the distal tubule which means one layer of epithelial cells the opposite one its called non-epithelial cells of distal tubule but the name of the those cells which are attach to the endothelial cells is macula densa. * Macula densa their function different from the epithelial cells of distal tubule, its secretion special substance but the function of the epithelial cells is reabsorption. * the endothelial cells of afferent arteriole(which attach to the macula densa) are different from the endothelial cells , theyre bigger and full of mitochondria.

* the juxtaglomerul apparatus has a very important function to control the GFR , to keep the filtration rate 125 ml/min . * Glomerular apparatus: this apparatus can be stimulated if the sodium concentration is low. -If the Sodium concentration in distal tubule is low this apparatus will be stimulated and it will secret renin and substance X (we still dont know that substance). -If the sodium concentration is high it will inhibit the secretion of this apparatus. Reabsorption is selective which means I need Sodium Ill take it. But also this activity depends on the speed of the flow, if the sodium goes very fast I might (as protein transporter) skip that sodium. But if the flow is slow, the probability of getting the particle back increases. *the plasma will flow through the tubular system in a speed, X . If the filtration rate is 125 ml/min they will flow with a speed of X/min in the tubular system.

Question: If the filtration rate is 50 ml/min, with which speed they will go through the tubular
system: higher, or the same or lower. Answer: lower.

Filtration-Reabsorption Related issues

Note that the normal filtration rate is 125 mL/min. What will happen if it increases or deacreases? If it decreases: Lets assume for any reason theres a decrease in the filtration rate, so instead of 125 ml/min lets say 70 ml/min. So 70 ml/min will go through proximal tubule with less speed, by go through proximal tubule and loop of Henle, the probability to reabsorbs Sodium is higher because the flow is slow(the proximal tubule and loop of Henle will take most of the Sodium), so when they reach this area the Sodium concentration will be lower (because the GFR is lower and the absorption is higher). *then when they go through the juxtaglomerul apparatus, macula densa will sense that there is low sodium concentration then they secret Renin and substance x , both substances they do dilatation of afferent arteriole and constriction of efferent arteriole (we dilate the input and constrict the output). dilate the input the blood flow will increase inside the glands and if you constrict the output the blood flow will be in the capillary morethe hydrostatic pressure , the net filtration pressure and the glomerulus filtration rate (GFR) will increase too. Until it reaches the normal level, the level of secretion of Renin and substance X will be normal.

If it increases: if we have the opposite situation, instead of 125 ml we have 200 ml/min, in this
case the flow of filtration in proximal tubule will be faster and that will make the sodium reabsorption less.

In this case the sodium concentration in this area will be higher than normal, and that will case an inhibition of Renin secretion and substance X , so dilatation of efferent and constriction of afferent. and that will decrease the hydrostatic pressure in the capillary of the glomeruswhich causes a decrease in GFR. Until it reaches the normal value the level of secretion and substance x will be normal.

Filtration Rate : A Closer View

*Each nephron has its own apparatusand its important to keep the filtration rate normal. And because of that if you decrease the blood pressure or increase the blood pressure from 70 mm mercury (which is below normal) to 160 mm mercury (which is higher than normal) the filtration rate will remain constant because of this apparatus; so thats why we always have 125 ml/min filtration rate.

Reabsorption Mechanism
I need it, I take it. I dont need it I give it to the urine simple as that. If we had 124 ml/min reabsorption flow, this miss is 1 ml/min excretion. Lets assume that 123 ml/min reabsorption flow so the rate of excretion will be 2 ml/min which means double the amount of urine output. So reabsorption should be controlled in order to keep the output normal.

What Do You Know About Tubular Reabsorption??

1. its huge. 2. Its selective. 3. It goes through multi ways .

When we say reabsorption we mean by that particles, chemicals, water and anything should go back to the blood.

In this figure we have tubular lumen, one layer of tubular epithelial cell, the basement membrane which contains the interstitial fluid, endothelial cells of capillary and the blood. The plasma here most of it should go back to the blood, toxic material should not go back to the blood. The way to go back is called trans epithelial transport, were talking about transport mechanism, in other words either active or passive, primary or secondary and facilitated or simple. (Active as endocytosis, exocytosis ) . Each particle in lumen goes through the cytoplasmic membrane of the epithelial cell, then it crosses the cytosol until it reaches the basolateral side of the epithelial cell, then it crosses the side of the membrane outside, then it moves in the basement membrane until it reaches the capillary. Finally it enters the capillary. (This is multi steps transport).

Question: How should I consider if the transport is active/passive reabsorb material?? Answer: If the particle or chemical or molecule of water crosses one of those steps actively ,
the whole reabsorption will be active. Note: All of the substances gets freely filtered because filtration is a random but the reabsorption is selective.

A: freely filter, not reabsorb and not secreted. B: freely filter, partially reabsorb and not secreted. C: freely filter, completely reabsorb and not secreted. D: freely filter, not reabsorb and completely secreted. Another scenario not listed in the figure above: freely filter, partially reabsorb and partially secreted. If we want to calculate the amount in A, B, C, D it is equal to Amount of Substance = filtered load reabsorption + secretion

Question: a student asked a question that we couldnt hear at all from the record but most
likley on how kidneys get rid of toxins and this was the professor answer (quite lengthy).

Answer: Lets talk about very toxic material x it will be dissolved in the plasma , if that toxic
material stays in your body , it will kill your cells , so we need to get rid that toxic material , so the kidneys clean the plasma 60 times/days. Each time the plasma comes to the kidneyes only 20% of the plasma moves from the capillaries to Bowmans capsule, so only 1/5 of that toxic material will be cleaned. Lets say these are hundred particles (of the toxic material). In the first cleaning round youll lose 1/5 (thats 20%) of the 100 particles, so youll lose 20 particles of the toxic material. In the second round, another

20 and so on. Youll lose 20% in each time. And theres another proberty for the kidneys thats the secretion. So by this, 20% of the toxic material will be filtered and another percent will be secreted, So in each cleaning round we wont only lose 20% of the toxic material but more that that due to the tubular system property of secretion. We clean the toxic material by Filtration not reabsorption and also by secretion). thats why physicians instruct their patients while giving them drug to patient will regarding the doses. If the drug is Penicillin the physician will tell the patient to take 1 tablet each 4 hours because the ability of the kidney to clean tha Penicillin is fast and by 4 hours of take the Penicilllin tablet the body will get rid of it 100%. If the drug is Amoxicillin the physician will tell the patient to take 1 tablet each 8 hours because the Kidneys cleaning ability fo Amoxicillin is slower that that of the Penicillin. If its Tetracyclin its a tablet each 12 hours, Gentamicin one single dose daily and so on. EL FIKRA EL 3AMMeh : Kidneys clean any toxic material by both Filtration and Secretion functions only.

Tubular Syestem and the reabsorption

Now Lets talk about the important materials of our life and how they behave in the tubular system of the kidney. Kidneys clean the plasma we already said that but whats there in the plasma? the majority is water, 90% of the plasma is water. Theres also Electrocytes ( , , , , ). Nuitrients, amino acids, fatty acids, proteins and other added substances to our bodies like drugs and toxic matrials also exist in the plasma. The tubular system will deal with each category dependently and differently. Electrocytes Sodium Floride (NaF) should be constant in the extracellular fluid. We should not have little amount of the NaF nor a great amount of it. Normally the kidneys will absorb 99.5% of the NaF back to our bodies only when we have the normal amount of it. But because what we eat tends to be salty most of the times the NaF amount is greter than the normal, thus, the sodium amount in the plasma will be greater than the normal. In this case the kidneys will absorb the normal amount of sodium and secret the extra sodium into the urine. Hydrogen hydrogen will cause acidosis if excess. And for the sake of keeping the pH constant, kidneys will secrete the hydrogen if excess. Little amount of hydrogen will cause alkalosis. And in this case, the Kidneys will switch its function to absorb more hydrogen back to the body. Water Normally, the kidney have the ability to absorb back the water by 99%. Food (nuitrients) Kidneys are able to take the glucose, amino acids, fatty acids and vitamins back 100%. Toxic material and metabolic waste

Urea, Creatinine, CHO3-, phosphate and all that stuff will be partially reabsorbed but not fully reabsorbed. Lets take the urea for example; the kidneys will absorb them back to the body by 50% and will secrete the other 50% out of the body into the urine. Kidneys wont absorb any amount back of the Creatinine to the body and will secrete the whole amount completely out into the urine. Kidneys will secret more than 70% of the Uric acid out into the urine.

Tubular system
as the most of the reabsorption processes occur in the proximal tubule, we saw that the sodium reabsorption part of this lecture is better listed in the proximal tubule part than anywhere else.

# Proximal tubule
being the first tubule in the tubular system; most of the reabsorption (and of course other processes) occur here. So as an example of a reabsorption process we will talk about Sodium. Sodium Reabsorption we will take Sodium Reabsorption as an example of how the kidneys reabsorption property and process, that occurs mainly in the tubular system. In the proximal tubule theres the major energizer for the sodium reabsorption process, the sodium-potassium pump and its located in the basolateral side of the cell not the luminal side. That means that the protein transporters for sodium in the luminal side are all passive for the sodium and we all can get that by Knowing the fact that sodium concentration is way higher than that of the inside (150 ml/M outside and 5-7 ml/M inside) and the gradient is abviously from in to out. According to this, the flow will be a Sodium influx from the outside to the inside but the cell will never allow the sodium amount inside it to increase above the normal, and thats why we have the sodium-potassuim pump. What does it do? It expellles the Na+ out, 3 Na+ out and 2 K+ in. So the first step in the sodium reabsorption is the Na+/K+ pump; expelling the Na+ outside the cell to the basement membrane and against the concentration gradient by using ATP as a source of energy. We often refer to such gradient as achemical gradient. So till now we can conclude that the sodium reabsorption by a chemical gradient so far. What will happen to the intercellular charge with the Na+/K+ pump working diligently? 3 Na+ out and 2 K+ in? The charge will be negative. And what will happen if the intracellular charge is negative and the Na+ is positive?? The cell will attract the Na+ by another mean not only the chemical gradient but also with what we call a voltage gradient, negative attracts positive and vice versa. So till now we know that theres two gradients that are involved in all this Sodium reabsorption dilemma; The chemical (1507) and the voltage (+-) gradients. And whats the osmolarity? We said that if you want to measure the osmolarity of any fluid you must know the Na+ concentration first because 80% of a fluid osmolarity state refers to its Na+ concentration. So if the Na+ is increased here not 150 ml/M but lets say 200 ml/M. Such increase will cause this area to be very hypertonic. The blue area in the figure is very hypertonic

while the yellow area that has lost its sodium is hypotonic. Whats next? Osmosis takes place. Water will follow the Na+ always and wherever it flows. The tight junctions you already learned about in previous lectures arent tight as much as you think. Because of some differences in forces of the osmotic pressure cells will get somehow separated and we will have something called a bulk flow of the filtrate: amount of the filtrate will go from the space to the basolateral side. This is not transport as much as its a filtration. So for now we know that the Na+ gets reabsorbed by the chemical gradient, the voltage gradient and the bulk flow. And Then in the Basement because of the huge amount of Na+, it will get inside the capillary by the means of simple filtration. So Na+ will be back in the blood and the blood circulation. This all occurs in the proximal tube only. So, in the proximal tubule 65% of sodium reabsorption occurs.

# Loop of Henle
it has 2 segments; ascending and descending. About 15% - 17% of reabsorption occurs in the loop of henle but theres almost no reabsorption of Na+ that occurs in the descending portion of it.

# Distal and collecting tubules

in the distal and collecting tubules the Na+ reabsorption gets controlled. If you noticed in the proximal tubule and the ascending limb of the Loob of Henle there was no control. Here in the distal and the collecting tubules theres a control in the reabsorption of the Na+ trough a hormone called aldesterone. Aldesterone function in controlling: In the distal and collecting tubules, aldesterone will allow Na+ to be reapsorbed and to get back to the body and its absence will inhibit the Na+ reabsorption. Lets take an example on this: theres an amount of sodium in your plasma. It will go through first the proximal tubule, then the Loop Of Henle. After getting out from there 90% of it is gone; reabsorbed. Now 10% of the

Na+ is under control in the distal and collecting ducts by aldesterone. This 10%, is it extra for your body or not? If its extra we aldestrone wont be secreted and this 10% will proceed to the urine and no further reabsorption will occur in the distal or collecting tubules. But if this 10% is needed for the body aldesterone will be secreted and this amount of Na+ will get reabsorbed in the distal and the collecting tubules. Thats why physicians make sure that hypertension patients never take a drug that contains aldesterone so extra Na+ wont be reabsorbed. proximal tubule 65%, Loop of Henle 20% and almost 10% in the distal and the collecting tubules as to get the most of the Na+ reapsorbed and back to the body.

Secondary Active transporters

Now in the proximal tubule Na+ reabsorption plays another big role in our lives. In the Luminal side there are huge numbers of facilitated Na+ transporters, Secondary Active Transporters. Transporters in the cytoplasmic membrane its for sodium. And the sodium outside the cell is huge in amount compared to the sodium inside. So the Sodium will flow inside the cell. This flowing of Na+ in and out of the cell will create energy in that transporter. This energy will be used for another substance to be actively transported. There are 2 types of these transporters: secondary active co - transporters and secondary active counter transporters. If a substance goes in the same direction of the Na+, this transporter is a co transporter. If the Na+ gets in and another substance gets out this is a counter transporter. If we say that a transporter transfer Na+ in passively and glucose in actively its a Secondary cotransporter and so on. By using the sodium influx, sodium transport we can transfer some other nutrients like glucose and amino acids, fatty acids and vitamins, which aid in their reabsorption processes. All of them ( the transporters ) are located in the proximal tubule because their function is to get back the glucose , amino acids , fatty acid , vitamins ( nutrients ) because GOD didnt want the nutrition to get wasted in the collecting duct , he wanted all of the food to go back to your body before even reaching the distal tubule.

Glucose reabsorption , Tmax and the curves

We dont have co-transporter for glucose or fatty acids or vitamins in the distal/collecting tubules neither in the loop of Henle but here they are very efficient in the proximal tubule , they get back 100% of your glucose and this reminds you of an important issue when we talk about active transport. Theres something called T max (transport maximum), WHAT IS THE Tmax? Simply , of I have a tube protein transporter active , lets say I have 100 protein transporter for glucose , SO that mean if 1 protein of glucose it will be occupied it cant carry another one. (you know about binding sites and how binding works). SO, if I have 50 particles of glucose so the 100 protein will utilize 50 glucose , If I have 90 particles of glucose 90 will bind . When I have 100 glucose I will occupy the whole protein capacity, this is the Tmax ( the full saturation ). If I have 100 particles and 1 this 1 will not find a

protein transporter so what happens to this particle? It will not be reabsorbed ( will proceed to the urine ) . In the loop of Henle theres no protein transporter they will end up in the Urine , thats why when we have a patient with diabetic mellitus (a disease where the glucose is higher than normal same of the glucose will get excreted in the urine. Now we will explain what will happen to the glucose and this will be applied to all the materials which are actively reabsorbed. Lets take particles of the glucose if its filtered , reabsorbed (completely or incompletely), if they reach the Tmax ( full saturation ). All these cases is shown in 3 curves : First one is the red one. we study the relation between the glucose in the plasma and the glucose in the filter Bowmans Capsule . I told you each minute we have 125 mL of plasma in the Bowmans capsule . If I told you I have 100 particles of glucose in each 100 mL of plasma , how many particles in Bowmans capsule in each minute ? 125 particle . NOW if I have 200 particles in each 100 mL . how many particles in Bowmans Capsule ? 250 . If I triple it the filtration rate m because filtration id talking plasma from here to Bowmans Capsule . So the relationship between filtrated glucose and plasma protein concentration is the straight forward relation . The more glucose in the plasma the more filter and this is the red line ( on the figure ) . But the glucose after Bowmans capsule will flow into the tubular system , in the tubular system ( proximal , loop of Henle and distal /collecting ) in the proximal tubular we will have a huge amount of glucose secondary active co-transporters to get it back . how much is that is the Tmax , the Tmax for glucose is 375 mg/min which means . if we filter 375 mg/min the co-transporter of glucose is occupied 100% which means if I take the re-absorption relationship not the filtration . reabsorption (the dotted curve) is different , if its less than the Tmax 100% will be back the Tmax is 375mg/min . If its 100mg they will be back in your body 376 mg/min; 375 back to your body and 1 mg out . This is the reabsorption relation 100% back until reaching the Tmax the extra will go to the urine. The amount of reabsorption is constant 375 but the extra is out. Now the third relation, the Excretion (green curve) : how much glucose in the urine. Before the Tmax, nothing will appear in the urine of the glucose amount. After Tmax any extras will be excreted out. So this will be the ratio or the amount of the glucose going outside the urine, if you increase the plasma glucose concentration. The normal glucose concentration is 100 mg /dl. And its very important that the glucose gradient stays normal. How we will keep the control? By insulin thats inside the body. If you eat a lot of sweet food that will not be100 mg only, youll get more. But if you eat an acceptable amount of sweet food no matter how much you eat the glucose concentration will not exceed 180md/dl. Let me ask you a question about the renal system. Whats the amount of glucose in the

Bowmans capsule? Its 180 as I mentioned. If you calculate the filtered flow it will exceed 250but 25 mg/min. is still under the T max of the glucose. So if you are normal no matter how much you eat glucose. The glucose will not appear in urine. But if you are diabetic and the insulin cannot control the amount of glucose in your blood so when you eat a sweet meal you will not reach 180 mg, youll exceed that so youll have a least 300 mg/dl of glucose. If we have 300 mg; whats the amount of glucose in the Bowmans capsule? 375mg/min. This is the Tmax. Thats why for those patients the glucose will start to appear in the urine. So this amount the 300 mg/dl is called: Renal plasma threshold. Before 300 mg/ dl in the plasma in the blood we are safe. We wont get the glucose out but after the threshold when every extra particle will be added to the urine. This applies to the glucose, amino acids and to every substance in the filtrate which are actively reabsorbed. But if its not actively reabsorbed its time dependent. One exception though, the sodium is actively reapsorbed but it doesnt follow these curves. Why? I told you 40% of the utilization of oxygen is for the Na+/ K+ pump. Because of that huge utilization, these curves dont apply to the sodium.

Wish you all the best of luck and thanks to everyone who helped Done by: Eman Idkaidek

Noha Ghazal