Regulation of GFR and Tubular reabsorption: Lecture Notes


Regulation of GFR:

1) Sympathetic system

2) auto regulation of afferent arteriole

3) juxtaglomerular apparatus

Tubular reabsorption:

Important principles regarding reabsorption

1) As mentioned before that each segment of tubular system has certain characteristics, which enable them to perform certain function as follow:

A/ proximal tubule: has extensive brush border which reflect large reabsorptive capacity, rich in mitochondria (which reflect the needs for ATP for active transport in these cells especially for Na+_K+ pump on the basolateral side), has both active and passive transport reabsorption

Rapid review for types of transport:

Passive transport ————- doesn’t need energy i.e. from high to low

Active transport ————— either primary: This need direct ATP energy, from low to high

or secondary active transport——- which needs energy stored as concentration gradient of Na+ ….here we have two substances , one of them is Na+ which cross from high concentration to low and this provide the energy needed for the carrier protein to move the second substance from low to high concentration

B/ the descending loop of Henle: has no brush border, very little mitochondria (reflect that there is no active transport in the basolateral side of these cells), has only passive water reabsorption

C/ ascending thick segment of loop of Henle: little and not well developed brush border, mitochondria present, has just active transport of (Na CL), there is no passive transport of water

D/ distal tubule: little and not well developed brush border, has a lot of mitochondria (but not like that for proximal tubule), has active transport

E/ collecting duct: poorly developed (absent) brush border, has no active transport (so we conclude there is no or little mitochondria), has passive water transport under hormonal control (ADH)

Note: I) when we say active transport we mean (Na+ _ K+ pump) on the basolateral side

II) Notice that the water is the main substance that is reabsorbed passively

2) Reabsorption of substances is highly related to reabsorption of Na, especially for water, sugars and amino acids

3) Na is always kept low inside tubular cells by primary active transport of Na _ K pump which is present in the basolateral side of tubular cell

4) Transport of substances in general is either by passive or active transport

5) Na_ K pump is present on the basolateral side of tubular system except for descending limb of Henle and very few present in collecting duct

6) The filtrate has isotonic osmolarity with plasma i.e. 300 mosm/L, it remain isotonic in the proximal convoluted tubule, but it become hypertonic relative to plasma in descending limb of Henle because this segment is permeable for water only and by this the filtrate there will loose water and become concentrated, and when reach ascending limb of loop of Henle it become hypotonic because this segment is permeable for salts only and not for water, by this diluting the filtrate

Note: remember that removal of just water from the solution make it concentrated (increased osmolarity), while removing of solutes (particles) only will result in dilution (decreased osmolarity)

7) Because Na+ inside tubular cells is always kept lower than that present in the filtrate, there is Na+ gradient which is very important for co-transport and counter-transport that happen during reabsorption and secreting of some substances like Na, K, H, glucose and amino acids

8) When Na reabsorbed from filtrate to inside of tubular cells it will create osmotic force that make water move to inside also by passive transport, and most of water reabsorption occur like this with out hormonal control except for ascending limb of Henle, distal convoluted tubule and collecting duct

Notice that how Na reabsorption is very important for reabsorption and secretion of other substances like (water, Na, K, H, glucose, amino acids), and all depend on creating Na gradient across the tubular cells

Water reabsorption:

1) Water is reabsorbed passively through out the tubular system except for ascending limb of Henle (no water reabsorption), and it happen with out hormonal control except for collecting duct where it need hormonal control (ADH) for water reabsorption (other wise it is impermeable for water)

2) Water reabsorption in the proximal tubule is passive and it is about 65% of the filtered water, this reabsorption occur iso osmotically, as to say, it is reabsorbed following the reabsorption of other substances (particles) so the osmolarity remain 300 mosm/L

3) Another 15 % of filtrate is reabsorbed in the descending limb of the Henle, this reabsorption occur just for water and there is no other substance reabsorbed associated with the water, in other word the filtrate will loose water and will be concentrated and hyperosmolar than plasma (more than 300 mosm/L). Now the remaining of the filtrate is 20% of original amount.


I) This amount of water reabsorption (80%) is not under hormonal control, but depends on the amount of water filtered only.

II) Don’t forget that descending limb of loop of Henle is permeable for water only

4) No water reabsorption in the ascending limb of Henle, because this segment is not permeable to water (ascending limb is only permeable for salts Na CL and K)

5) Remaining 20 % of filtered water is still high amount to be excreted in urine (about 36 liter), so it has to be reabsorbed in collecting duct but these segments especially collecting duct needs hormonal control (ADH) to be permeable for water, finally the excreted amount of filtered water is just about 0.5 % of original filtrate (about 0.5 to 1.5 L per day)

Note: if ADH (vasopressin) is not present, collecting duct will be impermeable to water

Medullar osmotic gradient and urine concentration:

1) When the filtrate pass through proximal tubule it has similar osmolarity to plasma (300 mosm/L) and water reabsorption is equal to solutes reabsorption so hat osmolarity of the filtrate remain isotonic with plasma

2) When filtrate pass through descending limb of Henle, which is permeable to water only, so that water reabsorption will result in concentration of filtrate (become hypertonic), this water reabsorption occur passively and due to that descending limb pass through hyperosmotic medulla

3) When we descend more and more in loop of Henle water is lost continuously making filtrate more concentrated and until its osmolarity reaches 1200 mosm/L in the end of descending limb, and by this, osmolarity is equilibrated with that of the deepest part of medulla (remember that osmolarity of the medulla begin at 300 mosm/L in the junction with medulla and increase gradually until reach 1200 mosm/L)

4) When the filtrate pass through ascending limb of Henle solutes like Na CL and K will be reabsorbed actively out of filtrate leaving the filtrate hypotonic, and thus whenever ascending up osmolarity will decrease until it reaches 100 mosm/L in the end of ascending limb (remember that ascending limb of Henle is permeable for salts only but not for water so the filtrate here does not equilibrate with the surrounding medullar osmolarity)


I) Some diuretics named as loop diuretics act on thick ascending limb of Henle preventing Na CL and K reabsorption and by this getting rid of  salts which will reduce blood pressure

II)* you may ask from where this medullary osmotic gradient formed? It is important to realize now that active transport of Na CL and K in the ascending limb of Henle is responsible for the initiation of medullary osmolarity gradient by pumping solutes from ascending limb to the interstitial fluid of medulla.

5) Active transport of salts in ascending limb to surrounding interstitial fluid of the medulla will create osmolarity difference between filtrate and medulla so that medulla has always greater osmolarity by (200) mosm/L for each level through ascending limb than osmolarity of filtrate, example if the osmolarity of the filtrate in the beginning of ascending limb is 1000 mosm/L then the osmolarity of surrounding medulla will be 1200 mosm/L and so on.

Role of ADH (vasopressin) in water reabsorption and urine concentration:

1) ADH work on collecting duct cells making them more permeable for water

2) If body has water deficit , as to say osmolarity of plasma increased, this will be detected by special receptors called osmoreceptors which will result in secretion of ADH, to conserve water in the body, which will make collecting duct more permeable for water and the amount of permeability is related to how much ADH released, the more ADH the more permeability and more water reabsorption and more concentrated urine and as follow:

In the presence of ADH, when the filtrate enter to collecting duct with osmolarity of 100 mosm/L it is considered hypotonic relative to surrounding cortex which has 300 mosm/L so filtrate will loose water trying to equilibrate with surrounding so osmolarity of filtrate may reach 300 mosm/L, then the filtrate will descend down the collecting duct passing through medulla which has increasing osmolarity, and in each level the filtrate try to equilibrate with surrounding medulla by loosing water until it may reach to 1200 mosm/L (if the amount of released ADH is enough) and by this producing small volume of concentrated urine to conserve water in body instead of being excreted in urine

3) If the body has water excess , this will result in decreased osmolarity of plasma which is detected by osmoreceptors resulting in the reduction of the ADH secretion, so that body loose water in urine as follow:

In the absence of ADH, When the filtrate pass through the collecting duct, which is impermeable to water now although there is osmolarity difference between filtrate (100) and surrounding cortex or medulla, there is no water movement, by this, producing large volume of diluted urine to get rid of excess water in the plasma

Conclusion: 80 % of water reabsorption through tubular system is not under hormonal control (in the proximal tubule and descending loop of Henle), and 20 % of water reabsorption is under ADH control in collecting duct.

Rennin –angiotensin- aldosteron system

1) When Na reabsorbed water will follow it, and also Cl will follow it by electrical gradient as to say, when salts conserved in the body they will lead to water retention in body and this will lead to increase blood volume and as a result increase the blood pressure and vise versa when body loose salts it will lead to reduction of blood pressure

2) Renin is secreted from juxta glomerular apparatus in response to (decreased plasma Na CL, decreased ECF and decreased blood pressure)

3) Angiotensinogen, present in plasma, is the precursor of angiotensin

Steps of the system:

1) When the stimulus present (decreased Na CL or ECF or blood pressure) rennin secreted from kidneys and will act as an enzyme on Angiotensinogen to convert it to angiotensin I and this will circulate in blood until reach to lung where there is an enzyme called angiotensin converting enzyme (ACE) which will convert the angiotensin I to angiotensin II

2) Angiotensin II has following functions:

a/ stimulate aldosteron secretion to (increase Na reabsorption and K secretion)

b/ make vasoconstriction for blood vessels so that increasing blood pressure

3) Aldosteron stimulate Na reabsorption in the proximal and collecting duct by enhancing Na insertion to Na channels and enhancing Na _K pump on basolateral side, and by this it is responsible of 8 % of Na reabsorption and imagine if it is absent or inhibited as some diuretics do how much Na will be lost each time filtration occur by accumulation effect leading to loose water also and by this reducing blood volume and thus blood pressure. Also Aldosteron is responsible for K+ and H+ secretion

Clinical example: when blood pressure decrease significantly for any reason, like when loosing blood, following events will occur more or less:

1- Baroreceptor will detect decreased blood pressure and will stimulate sympathetic system which increase blood pressure and reduce GFR which also lead to increased blood pressure by conserving water

2- Renin will be secreted which will lead to production of angiotensin II which by itself will make vasoconstriction and increase blood pressure also stimulate aldosteron secretion which will make water and salt retention and increasing blood pressure also (but notice that this mechanism of aldosteron needs time and so, it is useful for long term correction or adaptation for blood pressure)

3- when Na CL increase in plasma that will be detected by osmoreceptors as increased osmolarity which will lead to secretion of ADH and by this increase water reabsorption and more water (volume) conservation inside body to restore blood pressure

4) Rise in plasma K level also will stimulate Aldosteron secretion so that it will act on distal and collecting duct to increase secretion (normal plasma levels of K is required for normal function of the heart and CNS)

Sugar and amino acids reabsorption:

* Sugars, amino acids and other organic substances are filtered, but, reabsorbed 100 % by almost the same mechanism (co transport with Na) because body needs them

* Glucose is the example that we will take in details for this type of transport, is present in low concentration in the filtrate than in the tubular cells so it needs active transport

* Glucose is reabsorbed in the proximal convoluted tubule by a secondary active transport (as a co transport with Na), when Na pass from lumen to inside tubular cell, it do so as from high to low concentration and this gradient will provide the energy required for the carrier (which carry both Na and the glucose) to move the glucose from low to high concentration i.e. from filtrate to inside the cell

* Who keeps the Na concentration low inside cells? It is the Na _ K pump on the basolateral side, which utilize direct ATP energy and by this co transport could happen

* We call the protein that carry both Na and glucose, which is present in the luminal side, as a carrier

* We have several carriers, which are specific for each substance, so the carrier for glucose can’t be used for other substance and so on

* After glucose got inside cell it will move to the interstitial space by passive diffusion which is facilitated (facilitated by carrier but no need for energy) and for Na after being in, it will be actively transported to interstitial fluid by Na _ K pump

Role of carrier in transport & transport maximum:

When the substance is freely filtered its concentration in the filtrate will be equal to its concentration in plasma example if plasma glucose is 100 mg per 100 ml of plasma (100 ml is called deci liter), then the filtrate contain 100 mg per 100 ml, and by knowing that GFR is 125 ml per minute then we can calculate the amount of glucose filtered per minute that means we have 1.25 deci liter of filtrate per minute and for each deci liter we have 100 mg of glucose then we have 125 mg of glucose per minute

The quantity of a substance filtered per minute is called filtered load

Filtered load (for a substance) = GFR X plasma concentration of this substance

If GFR is constant, then the filtered load may change with according to the plasma concentration of this substance, examples:

— If glucose concentration 200 mg/100 ml —–then the filtered load is = 1.25 X 200 = 250 mg per minute

— If glucose concentration 300 mg/100 ml —–then the filtered load is = 1.25 X 300 = 375 mg per minute

So keep in your mind when substance increase in plasma its amount of filtrate will increase (when GFR constant)

Transport maximum:

* Transport carriers increase their work in transporting glucose when filtered load of glucose increase but, they has the feature that they can transport limited amount of glucose from tubules to cells as to say when filtered load of glucose increase to a certain level the carriers may reach their maximum capacity for transporting Glucose and at this level of filtered load we call the transport of these carriers as a transport maximum (Tm)

* We conclude from above that if the filtered load exceeded this transport maximum (Tm) the amount of glucose reabsorbed is constant and the extra amount of filtered load couldn’t be reabsorbed and so, they are excreted in urine

* Carriers for glucose will reach their (Tm) when the filtered load is 375 mg per minute that means plasma glucose level 300 mg / 100 ml (and by considering that GFR is constant 125 ml per minute), we call this plasma level of glucose at which the filtered load is equal to transport maximum for the carriers, as a renal threshold for glucose

Na reabsorption:

1) 99.5 % of filtered Na is reabsorbed

2) 65 – 70 % of filtered Na is reabsorbed in proximal tubule, 25 % is reabsorbed in ascending limb oh Henle and for both not under hormonal control, and 8 % is reabsorbed in distal tubule and collecting duct but under Aldosteron control

3) Na reabsorption is important in reabsorption of other substances and also for secretion of others like K+, H+ secretion

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