Lecture 1: Renal Transport Mechanisms Flashcards
5 distinct barriers for substance to be reabsorbed?
1) Leave tubular fluid by crossing luminal membrane
2) Through cytosol of tubular cell
3) Cross basolateral membrane of tubular cell to enter interstitial fluid
4) Diffuse through interstitial fluid
5) Penetrate the capillary wall to enter plasma
Why bother to filter 180L/day and then reabsorb 99% of it?
- Foreign substances are filtered into the tubule, but NOT reabsorbed into the blood
- Filtering ions and water into the tubule make regulation simple
Majority of substances are reabsorbed where; what are they?
Proximal convoluted tubule
100% of glucose, AA’s
70% of Water, Na+, K+ Phosphate, and Ca2+
50% Urea
What is reabsorbed in the proximal straight tubule?
Phosphate (15%)
Primary vs Secondary active transport?
Primary: coupled directly to an energry source (ATP)
Secondary: coupled indirectly to an energy source (due to concentration gradient of an ion)
Primary active transporters of the kidneys?
Na-K+ ATPase, Hydrogen ATPase, Hydrogen-K+ ATPase, and Calcium ATPase
Key element of proximal tubule reabsorption; location?
Na-K+ ATPase; basolateral membrane
What is tubular load and the calculation?
Amount of any substance(s) entering the tubule/min
TL(s) = P(s) x GFR
What 2 things does the operation of Na+-K+ ATPase accomplish?
1) Lowers IC [Na+] and increases IC [K+]
2) Creates low IC [Na+] and negative charge
Describe the Transcellular vs Paracellular route
Transcellular: substances move through the luminal membrane, cytosol, and the basolateral membrane
Paracellular: substances move between the tubule cells
Why is movement through the paracellular route limited?
Contain tight junctions, which are leaky and only allow some important ions (Ca2+, Mg2+, K+ and some Na+)
How do substances move through transcellular vs paracellular (transport mechanism)?
Transcellular: Passive diffusion or Active transport
Paracellular: Diffusion
What is the single most abundant cation in filtrate; how much energy is devoted to their reabsorption; almost always via what mechanism and route?
Na+; 80%; almost always active transport and via the transcellular route
Majority of Na+ ion reabsorption occurs through what channels on what surface?
Sodium leak channels on the apical surface (luminal membrane) of the proximal tubule cell
Sodium, H2O, and other substances are reabsorbed from the interstitial fluid into the peritubular capillaries by which forces?
Hydrostatic (Pi) and colloid osmotic pressure gradients (πc)
How does the diffusion of Na+ out of the cell using Na-K+ ATPase favor the movement of more Na+ into the cell?
The Na-K+ ATPase is working to get Na+ out of cell across the basolateral membrane, creating a low intracellular [Na+] and a negative intracellular electrical potential. This negative electrical potential in the cell attracts more Na+ from the tubular lumen to diffuse into the cell so that it can then be pumped out and into the interstitium for reabsorption into the capillary.
80% of the Na+ entering the tubule cells does so in exchange for what ion, via what transporter?
Exchange for H+ (secretion) via the Na-H+-exchanger 3 (NHE3) - Countertransporter/Antiporter
What is the exchange ratio for the NHE3 antiporter?
One Na+ is reclaimed from the lumen in exchange for one H+ ion
When H+ gets exchanged for Na+ by NHE3 you now have an acidic H+ ion in the lumen of the proximal tubule, what happens?
- H+ secreted into the filtrate combines with HCO3 —> H2CO3, which is quickly converted to H2O and CO2 via carbonic anhydrase
- CO2 diffuses back into the tubule cell cytosol where it combines with H2O to form H2CO3 in the presence of carbonic anhydrase. H2CO3 then dissociates into H+ and HCO3.
Once H2CO3 has dissociated in the tubular cell cytosol to form H+ and HCO3, what occurs?
H+ recycles through the NHE3 again, while HCO3 moves into the interstitial space via the NaHCO3 cotransporter
The NHE3 transporter is important for the reabsorption of what ions?
Na+, Cl-, and HCO3
Discuss chloride reabsoprtion
More H20 than Cl- is reabsorbed in the first 1/2 of the proximal tubule, which causes the [Cl-] in tubular fluid to increase about 20% along the length of the proximal tubule. This increasing concentration provides a chemical gradient that drives Cl- movement “passively” w/o need for additional energy expenditure, along the PARACELLULAR pathway.
What is present in the cell membranes of the thin descending limb, thick ascending limb, and collecting duct that determines the movement of H2O?
Thin descending: smaller amount of tight junctions, so paracellular movement of H2O occurs freely
Thick ascending/collecting duct: abundant tight junctions prohibit water movement
What prevents the transcellular movement of water?
Specialized epithelial cells in the apical membrane (luminal membrane), which are tightly packed with lipids, repelling or blocking water movement through the lipid bilayer.