Flashcards in Proximal Tube Transport Deck (30)
Review: 2 types of gradients that make water move across a membrane?
Hydrostatic and oncotic pressure gradients.
4 things that make solutes move across an epithelium?
Transepithelial (i.e. paracellular) electrochemical gradients.
Apical membrane-cell and basolateral membrane-cell electrochemical (i.e. transcellular).
Do tight junctions play a role in transepithelial ion transport? Which ones, specifically?
Yes. Claudins and E-cadherin mediate paracellular Ca++ transport.
If the Na+/K+ ATPase on the basolateral membrane of proximal convoluted tubule (PCT) epithelium is "primary active transport", what is "secondary active transport"?
How about "tertiary active transport"?
Secondary: H+/Na+ exchanger on apical membrane (brings Na+ in from lumen, moves H+ out).
Tertiary: HCO3-/Cl- exchanger (bicarb follows H+ out into lumen, Cl- comes in).
Note these steps don't require energy.
What are the most metabolically active areas of the nephron?
The most hard-working areas are the medullary thin and thick ascending limbs and the distal convoluted tubule.
But the PCT does a lot of work too.
What 2 solutes are reabsorbed earliest and most avidly in the PCT?
Glucose and amino acids
(lots of bicarb is reabsorbed, but that occurs more slowly)
How does the ratio of tubular [Na+] vs. plasma [Na+] change along the length of the PCT?
As both Na+ and water are reabsorbed, the [Na+] stays pretty similar to that in the plasma throughout the PCT... but it does increase slowly.
How does [Cl-] vary across the length of the PCT?
Cl- is not reabsorbed much at first, so the concentration increases like that of inulin would (due to water reabsorption).
Further downstream Cl- begins to be absorbed, and the concentration increases at a much slower rate.
Is PCT water permeability determined by vasopressin?
Nope. It's just always very permeable to water.
(and thus urine remains nearly isotonic to plasma along the PCT - any movement of solute is followed by water)
What membrane molecules make the PCT so permeable to water?
Aquaporins, specifically AQP1 (and AQP7)
What would a defect in AQP1 cause?
Large volumes of dilute urine, as water could not be absorbed from the PCT (and the thin descending loop of Henle).
Is most of the water reabsorption in the PCT transcellular or paracellular?
Is there a Na/Cl cotransporter in the PCT?
No. Cl- transport is largely paracellular, driven by an electrochemical gradient that's positive in the lumen of the late PCT.
2 apical transporters involved in glucose reabsorption? Where are they? How are they different?
SGLT2 - in the PCT - high capacity, low affinity (Coupled to 1 Na+).
SGLT1 - the pars recta - low capacity, high affinity (coupled to 2 Na+).
What 2 basolateral glucose transporters are used? Where are they?
Pars recta: GLUT1
About high does plasma glucose have to be in order for glucose to appear in the urine?
(urine glucose isn't a great way to monitor diabetes)
What drives phosphate resorption?
Cotransport with Na+.
3 things that decrease phosphate reabsorption?
PTH (parathyroid hormone).
High phosphate intake.
2 things that increase phosphate reabsorption?
Failure to reabsorb what amino acid will give you really bad kidney stones?
What's weird about urate handling in the kidney?
It's all reabsorbed, then it's secreted, then mostly it's reabsorbed again.
(too much reabsorption -> gout. Too much excretion -> kidney stones)
Is bicarb reabsorbed as bicarb?
Nope, it's converted with a H+ by carbonic anhydrase to CO2 + H2O.
CO2 + H2O enter the PCT cell, where another carbonic anhydrase converts it back to bicarb. Bicarb and Na+ are cotransported into the blood.
How is Ca++ reabsorbed in the PCT, and where within the PCT does this happen?
Ca++ is reabsorbed paracellularly via Claudin-2.
This happens in the late PCT, when the lumen has a + charge.
(50-60% of Ca++ reabsorption happens in the PCT.)
What percentage of Mg++ is reabsorbed in the PCT?
What happens to K+ in the PCT?
A small amount is secreted.
Mostly it's absorbed paracellularly (via "solvent drag" early in PCT, passively in late PCT when there's more luminal + charge)
How are big molecules reabsorbed in the PT?
Endocytosis via the AMN-Megalin-Cubulin complex...
Where is the ammonia (NH4+) that reaches PCT lumen made?
How does it then get to the urine?
Largely in the mitochondria of PCT cells.
The mitochondria convert glutamine to glutamate to alpha-ketoglutarate, producing 2 NH4+...
Ammonia enters the urine either by an Na+/NH4+ exchanger, or diffusing as NH3.
What happens to NH4+ made by kidney that gets into the blood?
It's transported to the liver, where it's made into urea.
2 types of proximal tubule diuretic?
Osmotic diuretics (mannitol, high levels of glucose)
Carbonic anhydrase inhibitors (more on this later, I assume)