This lesson explores how sodium is regulated along the proximal convoluted tubule (PCT). It focuses on the transcellular and paracellular pathways, driving forces, the role of the sodium-cotransporters and the sodium/hydrogen exchanger (NHE3), and carbonic anhydrase. It also discusses how acetazolamide acts as a diuretic by inhibiting NHE3-dependent sodium reabsorption. For help preparing for an exam on this and other topics, visit
The proximal tubules reabsorbs between 65 and 85 percent of the filtered sodium load that means for an average filtered sodium load of 25,000 millimoles per day the proximal tubule reabsorbs anywhere from 16,000 to 21,000 millimoles which is why reabsorption along this segment is often referred to as bulk reabsorption sodium reabsorption along the proximal tubule
Occurs by trans sailor and para sailor routes however most occurs by the trans cellular route which includes a number of sodium dependent code transporters like sodium glucose sodium amino acid sodium phosphate and sodium organic acid co transporters as well as the sodium hydrogen exchanger or nh iii these types of transporters rely on the sodium electrochemical
Potential which is established by the sodium potassium atpase and the potassium permeability of the basolateral membrane the distribution of these sodium dependent code transporters along the proximal tubule is heterogeneous for example all of the glucose and amino acids are reabsorbed along the early or s1 segment while about 80% of the bicarbonate and phosphate
As well as 50% of the organic acids are reabsorbed along the middle or s2 segment the straight or s3 segments also reabsorb sodium however it plays a central role in secretion now this heterogeneity creates a lumen negative potential in the early proximal tubule while it creates a lumen positive potential in the middle and late proximal tubules a lumen negative
Potential facilitates the para cellular secretion of sodium into the lumen while a lumen positive potential facilitates the parasail reabsorption of sodium from the ultra filtrate overall the lumen positive potential is more prominent of all the sodium dependent code transporters along the proximal tubule the sodium hydrogen exchanger or nh iii accounts for much
Of the trans cellular sodium reabsorption as well as bicarbonate reabsorption now the sodium hydrogen exchanger transports one so i on into the cell in exchange for one hydrogen ion the intracellular hydrogen ion came from the conversion of carbonic acid which yielded one hydrogen ion and one bicarbonate ion this conversion is dependent on the enzyme carbonic
Anhydrase – as for the intra say their bicarbonate ions they’re transported out of the cell across the basolateral membrane by the sodium bicarbonate co transporter or nbc 1 the carbonic acid that yielded the hydrogen and bicarbonate ions was derived from one water molecule and one carbon dioxide molecule which came from the luminal fluid the water molecule moved
Across the apical membrane via the aquaporin type one water channel or a kewpie one while the carbon dioxide diffused across the lipid membrane the luminal water and carbon dioxide molecules came from the breakdown of carbonic acid by the enzyme carbonic anhydrase for which is located in the extracellular side of the apical membrane now the lumen carbonic acid
Was derived from one hydrogen ion and one bicarbonate ion the hydrogen ion came from inside the cell and was transported into the lumen by the nh iii co-transporter while the bicarbonate ion came from the ultra filtrate carbonic anhydrase inhibitors like acetazolamide are used to treat acute altitude sickness as well as glaucoma however acetazolamide indirectly
Inhibits nh iii dependent reabsorption of sodium and bicarbonate because it inhibits carbonic anhydrase – which leads to the reduction in intracellular hydrogen and bicarbonate ion concentration the decrease in intracellular hydrogen ion concentration then inhibits the nh iii exchanger as a result acetazolamide reduces nh iii dependent sodium reabsorption which
Leads to an increase in the osmolality of the ultra filtrate along the proximal tubule this in turn reduces the driving force for water reabsorption along this segment which results in increased urine output or polyuria this is why carbonic anhydrase inhibitors are often referred to as osmotic diuretic because the proximal tubule reabsorbs sodium and water equally
The osmolality of the luminal and interstitial fluid remain the same along the proximal tubules as sodium is reabsorbed this type of reabsorption is often referred to as iso osmotic with iso meaning same and osmotic mean osmolality in summary the proximal tubular reabsorption load it does this primarily via translator pathways that include sodium dependent code
Transporters and the sodium hydrogen exchanger also nh iii dependent sodium reabsorption is dependent on carbonic anhydrase activity which also plays a role in bicarbonate reabsorption then finally reabsorption of sodium is iso osmotic since sodium and water reabsorbed equally along the proximal tubule
Transcribed from video
Sodium Regulation: Proximal Convoluted Tubule By Lance Miller PhD