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Proximal Tubule Transport Notes

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Tubular transport Advantages of filtering and then reabsorbing
-only transporters for those essential solutes which must be recovered are requiredless than what is needed if adapted to excrete waste
-water balance is facilitated by using reabsorptive process for H20 rather than secretory one-energetically advantageous as many other solutes can be recovered in association with reabsorption of sodium
-Reabsorption of solutes along the renal tubule based on the Ussing model- dual membrane model created by tight junctions: Basolateral surface has Na/K ATPase, K channels- recycling K+ , apical membrane has a very high permeability to sodiumallows for vectorial transport- tight epithelium
-leaky epithelium- large amount of cotransport, antiport carrier proteins found on apical membrane that are coupled to Na+ influx down electrochemical gradient set by Na/K ATPase-Evidence: Increase in sodium reasborption, leads to increase in oxygen consumpation Role of different nephron segments Proximal tubule

Descending limb of loop of Henle Ascending limb of loop of Henle

Early distal tubule Late distal tubule and collecting duct

Absorbs via carriers
-Na+ , Cl- , HCO3- , Ca+ , glucose, amino acids water by osmosis Absorb via solvent drag
-K+, Ca2+ ,Mg2+
Secretes
-organic anions and cations using carriers Absorbs water through channels Absorbs via carriers
-Na+, Cl- , HC03Absorbs via paracellular route Na+, K+, Ca 2+, Mg 2+
Absorbs using carriers Na+, ClAbsorbs through channels Na+, Water Absorbs through carriers Urea Secretes using channels K+
Secretes using carriers

H+

PROXIMAL TUBULE STRUCTURE- BULK REABSORPTION
-Split into three sections : S1, S2, S3- S1 and S2 (convulted tubule), S3 (straight)
-Epithelia- polarised by prescence of tight junctions, asymmetric distribution of cotransport proteins and channels results in vectorial transport
-Brush border microvilli on the apical membrane- increase surface area for reabsorption, allows more cotransport proteins to be packed on the surface , one cell type
-Large amounts of mitochondria, microfilaments
-Leaky epithelium
-High permeability to ions through the paracellular pathway, low transepithelial potential difference
-High water permeability due to prescence of large number of aquaporins
-Reabsorption is isotonic- there is never an osmotic gradient present, as solute moves in water also follows due to high permeability- the sodium concentration in the reabsorbate is the same as that in the plasma-Experiment: Stationary microperfusion technique- solutions of various Na+ conc were entered into the proximal tubule lumen of amphibian proximal tubules- ratio of Na flow and rate of fluid reabsorption are constant and is equal to osmolality of lumen Mechanism of bulk reabsorption There are two transport route: Transcellular and paracellular i) First half of the proximal tubule
-Na+ uptake is coupled with organic solutes (glucose and amino acids), bicarbonate, phosphate through a transcellular route, transported into the cell via Cotransporters
-The chemical driving force for the influx of Na+ is created by the Na/K ATPase pump, 3 Na+ out and 2 K+ in on the basolateral membrane which creates a low concentration gradient of Na+ within the tubular epithelial- this allows Na+ to diffuse down its concentration gradient Evidence: Na+ reabsorption is varied experimentally, and measures renal oxygen consumption- the result is a straight line relationship
-There is also an electrical driving force, as the resting membrane potential of the tubular epithelial cells are -70mv, so the driving force of Na+ = Em-Ena = -70-60mv

= -130mv. The main ion that is responsible for setting up the negative resting membrane potential is K+ ions which diffuse out into the interstitium via ROMK K+
channels found on the basolateral membrane So Na+ transported down the electrochemical gradient S1 segment some of the Na+ are secreted back into the lumen via the paracellular route due to the transepithelial gradient being -3mv: some animals this contributes to 1/3rd of the Na+ being reabsorbed ii) 2nd Half of proximal tubule
-Na+ uptake is coupled with Cl-Paracellular route- where the main driving force is the electrical gradient- in the S1 segment the transepithelial potential difference (lumen to basolateral) is -3mv, resulting in the back leak of Na+ into the lumen (some animals-1/3 rd of the Na+
transported back into the lumen), S3 segment the transepithelial gradient is +3mv (so Na+ reabsorbed) Transport a) 1st half of proximal tubule relies on Na co transportation- transcellular uptake
-variety of cotransporters in the apical membrane that couple downhill uptake of Na+ with the uptake of solutes. Most of the cotransporters are electrogenic and carry a net positive charge into the cell
-Cotransporters exploit the downhill Na+ gradient created by the apical cell membrane, created by Na/K pump in the basolateral membrane. The flux of sodium into the cell is also favoured by the electrically negative cell interior established by K+ channels which also recycles K+
-2/3rd of the filtered sodium reabsorbed, 100% of the glucose, 99% of the amino acids, majority of HC03-The Sodium ions reabsorbed into the cell are extruded into the blood via the Na/K pump or the Na/HC03 Co transporters found in apical membrane i) Na/Glucose cotransporter (SGLT)
-Couples the movement of D-glucose and Na+ from the lumen to the proximal tubule cell-Phloridzin: inhibits SGLTs
-S1 segment, high capacity/low affinity transporter SGLT2- mediates apical glucose uptake- Na/Glucose stochiomery 1:1

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