The Tubular Maxima Mechanism of Reabsorption

Glucose, amino acids, water soluble vitamins, and some small plasma proteins are completely reabsorbed from the proximal tubule against their concentration gradients.  However, the threshold for re-absorption (maximum re-absorption rate) can be exceeded, beyond which no additional substance (glucose for example) can be reabsorbed (mg/min reabsorbed).  Because there is an upper maximum rate at which these substances can be reabsorbed, the secondary active transport mechanisms which reabsorb these substances are known as "tubular maxima" mechanisms.  Normally, substances reabsorbed by tubular maxima systems are completely, or very close to completely reabsorbed by the time the filtrate reaches the end of the proximal tubule.  This occurs even though very little control is exerted within the proximal tubule, where an isotonic solution is reabsorbed from an isotonic solution (the initial renal filtrate), into an isotonic solution (plasma).  Thus, ion concentrations do not routinely change much in the proximal tubule.  Substances left behind following absorption of H2O are increased in concentration as they pass into the distal tubule and collecting duct.  There is considerably more control over absorption exerted in the distal tubules and collecting ducts.

Let's consider the tubular maxima for glucose in order to see how tubular maxima mechanisms work.  Glucose is an excellent example of a substance which is 100% absorbed by the end of the proximal tubule.  We all know that glucose does not normally appear in urine (unless someone suffers from diabetes mellitus).  There is, however, a threshold beyond which glucose cannot be absorbed "any more quickly."  This threshold rate of reabsorption, or "tubular maximum for glucose" is denoted as TMG.  The kidneys can reabsorb glucose no faster than 300 mg/min!

Figure: Tubular Maximum for Glucose Re-absorption

We know that GFR = 125 mL/min

Suppose [Glucose]plasma = 1 mg/ml

Then, glucose filtration rate = 125 mL/min X 1 mg/mL = 125 mg/min

At this glucose filtration rate, glucose is usually not present in urine.  You must see some in the urine to know you have exceeded threshold in order to determine tubular maximum, but you must artificially increase glucose to do this.  Usually, it is necessary to exceed 3 mg glucose/ml plasma, resulting in filtration of about 375 mg of glucose/min and the appearance of 25 mg/ml in the urine.

Now, we have the information necessary to determine TMG:

Assume that 125 ml of plasma is filtered per minute.  Plasma glucose is artificially elevated and has been measured as 3 mg/ml.  We know that glucose is a very small molecule that is readily filtered at the kidney so we are safe to assume that all the glucose is being filtered at the glomerulus.  Thus, we are safe to assume that glucose is being filtered at 375 mg/min (125 ml/min X 3 mg/ml).  We know that, under ordinary circumstances, the kidney is reabsorbing a lot of glucose, because glucose does not ordinarily appear in urine.  Now that we have elevated plasma glucose to 3 mg/mL,  we check and find glucose present in the urine at a concentration of 25 mg/mL.  However, we also notice that with the appearance of glucose in the urine, urine production has tripled as a result of the osmotic diuretic effect of glucose.  Urine production is now 3 mL/min.  Glucose being lost in urine can be calculated as:

glucose is being lost in urine at 75 mg/min (25 mg/ml X 3 ml/min)

So now, let's figure out just exactly what we have done!  We have increased glucose to 3 mg/mL in the plasma.  We know that we are now collecting urine at a rate of 3 mL/minute with a glucose concentration of 25 mg of glucose/mL of urine.  That means that 75 mg of glucose is escaping the kidney every minute!  But we also know that the GFR is 125 mL/minute.  If plasma glucose is 3 mg/mL and GFR is 125 mL/min, then the kidney is filtering glucose at a rate of...

3 mg glucose/mL plasma X 125 mL/min = 375 mg glucose/min

OK, so now we know that the kidney is filtering glucose at a rate of 375 mg/min and losing glucose at a rate of 75 mg/min.  Of the 375 mg glucose being filtered every minute, the kidney must be retaining 300 mg of glucose/minute.  This must be the tubular maxima for glucose re-absorption at the kidney!  The absorption rate (TMG) of glucose can be calculated as total glucose filtered minus total glucose lost to the urine (ie. the amount filtered minus the amount not reabsorbed).

375 mg glucose filtered/min - 75 mg glucose/min in the urine = 300 mg reabsorbed/min

Thus, TMG = 300 mg glucose/min reabsorbed.  Normally, of course, glucose re-absorption considerably exceeds filtration.  Glucose will generally appear in the urine only when plasma glucose exceeds 3 mg/ml.  Don't forget, whenever glucose appears in the urine, the volume of urine output will increase!  Also remember that the reason that glucose sometimes appears in the urine of persons with DM is not usually because of a problem with the kidneys, but rather because plasma glucose concentrations are so high (hyperglycemia), that the rate of filtration of glucose at the kidney exceeds the TMG.

But once reabsorbed into the proximal tubule cells by a tubular maxima mechanism... how do these substances get back into the blood?

Glucose is re-absorbed from the lumen of the neprhon back into the cells of the PCT by secondary active transport, linked to sodium ions.  Now that the glucose is inside the cells, the glucose still has to get back into the blood.  The glucose now diffuses from inside the PCT cells into the interstitial space through "facilitated diffusion" proteins located in the basal membrane of the PCT cells.  Finally, the small glucose molecules are pulled into the porous peritubular capillaries by solvent drag driven by protein oncotic pressure.  The protein oncotic pressure is from the high concentration of protein in the peritubular capillaries.

So... glucose goes on a wild ride at the kidneys... first, filtered at the glomerulus, then re-absorbed into the PCT cells by secondary active transport linked to the sodium gradient, then transported across the basal membrane of the PCT cells by facilitated diffusion, and then taken up from the ISF into the peritubular capillaries by solvent drag driven by protein oncotic pressure.  Man... what a ride!!!

Reabsorption of Bicarbonate... a little bit different story!!!

Bicarbonate ions are very important buffers, but they are small and freely filtered into the renal filtrate.  About 90% of the bicarbonate ions are reabsorbed in the PCT... but they are reabsorbed in an interesting way not involving a tubular maxima mechanism.  As bicarbonate is filtered into the renal filtrate, the bicarbonate molecules are broken down into carbon dioxide (CO2) and water (H2O) molecules.  The carbon dioxide passively diffuses back into the cells of the PCT.  Once inside the cells of the PCT, the carbon dioxide combines with water, a process stimulated by carbonic anhydrase, to form new carbonic acid.  The carbonic acid then dissociates to form bicarbonate ions and hydrogen ions.  The bicarbonate ions diffuse back into the body through facilitated transport proteins in the basal membrane of the PCT cells... and the hydrogen ions are secreted back into the renal filtrate by Na+/H+ exchangers in the PCT.

David Currie.
Copyright 2000. All rights reserved.
Revised: January 05, 2009