Consider that the composition of the glomerular ultrafiltrate is basically that of deproteinated plasma. Harris et al micropunctured some rat tubules and determined that the concentrations of sodium chloride and phosphate was basically the same as in the blood. On top of that, bicarbonate and all the other slightly-larger-but-still-small molecules such as amino acids water-soluble vitamins and glucose also end up in the ultrafiltrate.
The proximal tubule heroically reclaims these treasures for the organism. The cells of the proximal tubule are singlehandedly responsible for reabsorbing all the protein and peptide fragments that managed to sneak across the glomerular border.
Amid all that activity, the cells of the proximal tubule manage to find the time to contribute essential metabolic activities, such as the activation of Vitamin D. According to the nomenclature outlined by Kriz et al , there are several geographical territories even in this little patch of glomerular real estate.
Specifically, you have:. Of course, that fat brown toothpaste-looking tube in the diagram is completely unrelated to the true scale and shape of this thing. For a true geometrically accurate representation of this part of the tubule, we can turn to Zhai et al , whose 3D reconstructions of micro-sliced mouse nephrons can give us a true sense of scale and length:.
The sides of the cells, where they connect to one another, are topographically quite complex, in a way that maximises their lateral membrane surface area. At the apex, the cells are connected with each other via rather simple smooth membranes, but as you go further from the tubule lumen, you see the lateral membrane connecting these cells become more and more convoluted.
Each basal cell therefore looks like some kind of marine echinoderm, with tiny branching foot processes interlocking with those of a neighbouring cell:. The events and activities in the proximal convoluted tubule are so numerous that it is easy to get lost in them.
What follows is an oversimplification, made necessary by the need to remain sane. The proximal tubule cells have a vast basolateral surface area, and it is bristling with these ATP-powered pumps.
According to this nice bar graph from Doucet , the proximal convoluted tubule is where this activity is maximal at least in the proximal nephron. The constant removal of sodium from the basolateral surface allows the constant movement of sodium out of the tubule lumen.
With the ATPase pumps so numerous, the flux of sodium can be truly massive in scale. This makes sense, as the proximal tubule might see about 28, mmol of sodium per day. This gradient for sodium is used to co-transport basically everything else. Numerous apical co-transporters exist, acting either to symport anions or antiport cations.
For example, anionic amino acids and glucose are co-transported, whereas hydrogen ions are exchanged. The number, diversity and function of these channels boggles the imagination. For the bewildered CICM trainee, it is not essential to know each and every detail here. The main fact to internalise is that the movement of sodium is required for the movement of all the other solutes.
As already mentioned, there's no need to laboriously memorise every apical transport protein, but there's a few worth knowing about. Some of these are drug targets, some are uniqye to the proximal tubule, and some are necessary for the understanding of other aspects of renal physiology.
In short:. The specifics of that acid-base manipulation here will be left for another chapter, but, in order to simplify revision, one may be reminded that the proximal tubule is where brush border carbonic anhydrase is responsible for the reabsorption of bicarbonate, which it converts into CO 2. This is the step susceptible to pharmacological manipulation by acetazolamide , and the site of type 2 renal tubular acidosis :.
The co-transport of sodium out of the tubule lumen decreases tubular fluid osmolality, as compared to that of extraluminal fluid. This produces a net movement of water out of the tubule, by all sorts of pathways.
Some movement is paracellular through the supposedly tight junctions and some is facilitated by aquaporins in the apical membrane.
As the result of this, the tubular fluid remains iso-osmolar over the length of the proximal tubule. One membrane side of the cell faces the tubule, the other faces the bloodstream.
This resulting lack of sodium creates a diffusion gradient within the cell. Sodium within the tubule fluid will diffuse along this gradient into the cell, acting as a cotransporter for other important molecules such as glucose or water. These molecules are brought into the cell along with sodium. Once inside, sodium is pumped out, whilst glucose and water diffuse out into the blood along their gradients. Selective re-absorption ensures important molecules such as water and glucose for respiration are retained rather than excreted, to be stored or used immediately.
Answered by Holly R.
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