Proximal Tubule Flashcards
Solutes that are reabsorbed via active transport … have 3 distinct characteristics?
- Competitive inhibition - compete with other solutes for transporter
- Metabolic inhibition
- Transport maximum - transporters get saturated (glucose)
How is urea reabsorbed (passive or active)
Passive
As water is reabsorbed… the concentration of urea increases…thus generating a gradient for passive reabsorption
Major characteristic of passive solutes
Rate or reabsorption decreases and rate of excretion in the urine INCREASES as the urine flow increases
Are urine flow increases why does urea reabsorption decrease
Water reabsorption decreased…so there is less of a urea gradient to drive passive reabsorption
Proximal tubule reabsorption levels for key solutes
67% NaCl and water
80-85% HCO3-
All of filtered glucose and amino acids, and inorganic ions like phosphate and sulfate, and organic acid anions like lactate, acetate, succinate, and citrate
Also sire for isosmotic fluid reabsorption
Location of Na/K ATPase
Basolateral membrane in early and late PT
Location of Na/H exchanger
Early and late PT (apical membrane)
Mediates reabsorption of HCO3
Net lumen transepithelial potential gradient in early proximal tubule
Negative (-4mV)
Net effect from Na+/solute cotransporter and Na/H exchanger
Helps drive a small amount of passive Cl- reabsorption by the EARLY PT
Major mechanism of Na cell entry in LATE proximal tubule
Na/H exchanger
Working in parallel with the an apical membrane Cl/anion exchanger
Anions = OH, HCO3, and formate…
These anions combine with the H+ that was pumped out and recycle back into the cell…dissociate…and thus continue to drive Na+ entry into the (Na/H exchanger)
What drive the Cl-/anion exchanger in the LATE proximal tubule?
The early proximal tubule…the major players are the Na/solute and Na/HCO3 reabsorption…
Thus there is high concentration of Cl- in the LATE proximal tubule
Thus…driving the Cl-/anion exchanger
—Cl into cell and anion into tubule
…also drives passive Cl reabsorption through paracellular pathway (with Na+)
Lumen transepithelial potential gradient in the LATE proximal tubule
Positive (+4mV)
Due to the increase reabsorption of Cl-
Mechanism for HCO3 reabsorption in the proximal tubule
- H+ secreted into tubule lumen (Na/H+)
- Combine with filtered HCO3 —> carbonic acid (H2CO3)
- Carbonic anhydrase (apical membrane): H2CO3 —> H2O + CO2
- CO2 diffuses into cell…where it is hydroxylated (addition of OH-) by CA in cyotplasm —> HCO3
- HCO3 exit through basolateral membrane via Cl/HCO3 exchangers and Na/HCO3 cotransporters
Carbonic anhydrase inhibitors
Class of diuretic
Acetazolamide
Inhibit CA that is located in the apical membrane and cytoplasm
So…inhibit the reabsorption of Na+HCO3-; NaCl, and water
Results in an increase in urine flow and urinary sodium excretion
Luminal hypotonicity mechanism of water reabsorption
As Na+ and other solutes are reabsorbed from the tubular fluid into the interstitial fluid…
The tubular fluid becomes hypotonic, with respect to the intersitial fluid and the plasma
Thus the PT generates a water gradient for passive movement into interstitial fluid…
Then it is pick up into peritubular capillary plasma due to oncotic pressure in capillary
Axial anion asymmetry mechanism for water reabsorption
Consequence of the differences in the Na/solute transport in the early and late PTs
Early = Na+ mostly reabsorbed with glucose, amino acids, inorganic anions, and organic acids anions and HCO3….
Creates a low HCO3 and high Cl- in LATE proximal tubule…
The HCO3 in the interstitial fluid provides a osmotic driving force for water to be reabsorbed
Effect of vasoconstrictor hormones
ANGII, catecholamines
Stimulate PT reabsorption of NaCl, NaHCO3, and water
Vasodilator hormones (renal) effect
Dopamine
Inhibit PT reabsorption of salt and water
starling forces =
The oncotic pressure in capillaries that will bring water and things dissolved in that water in the interstitial fluid into the capillaries
Factors that decrease plasma protein levels =
Like ECF expansion,
Inhibit movement of water from interstitium into the capillaries…
This increases hydrostatic pressure in the interstitial fluid … which is thought to increase the permeability of the tight junctions between the proximal tubule cells
…increasing solutes and fluid diffusing back into the tubule and excreted back into urine
NET effect = decrease salt and water reabsorption
Major mechanism for isotonic saline to increase ECF and urine flow and urinary Na excretion
PT reabsorption of water and salt is particulary determine by what
GFR..
Increased GFR = increase PT reabsorption rate
Does this to maintain a fractional reabsorption rate of ~67%
2 major mechanism that PT to maintain constant fractional reabsorption of water and salt
- Changes in the delivery of NaCl and solutes in the apical membrane …. more delivered —> more transporters are stimulated to reabsorb
- Involves changes in Starling Forces…
Ex: if GFR increase 50% but RPF constant…GFR/RPF increases (filtration fraction)
….so more oncotic pressure in capillaries….increase in net solute and fluid reabsorption in PT
Increases in filtration fraction —>
Increases in PT solute and fluid reabsorption
