Flashcards in Distal Tube Transport Deck (30):
3 things that are at higher concentration in the pars recta than in the blood (i.e. right before entering the thin descending limb of the loop of Henle)?
Why are they higher?
Cl-, due to bicarb resorption in PCT.
K+, due to K+ secretion into pars recta.
NH4+, due to synthesis in PCT.
Do thin limbs of the loop of Henle do much active transport?
Nope, not much at all. It's all passive transport.
What are the permeabilities to water and solutes like in the thin descending and thin ascending limb?
Thin descending: very permeable to water, not permeable to salts (water comes out, concentrating urine).
Thin ascending: not permeable water, very permeable to salts (Na/Cl comes out).
What, broadly, is the function of the thick ascending limb?
Dilute the urine.
What's the notable, powerful transporter in the thick ascending tubule? What does it do?
Na+, K+, and 2 Cl- symporter.
What creates a + charge in the lumen of the thick ascending tubule? What transporter mediates this?
K+ leaking from cytosol back into lumen.
This happens via ROMK channels.
What creates the Na+ gradient that allows NKCC2 to work?
Na+ pump in the basolateral membrane.
What's a drug that inhibits NKCC2?
Furosemide -it's a very powerful diuretic.
If a patient has a defect in ROMK, what would be effect on urinary Ca++? Why?
Urinary Ca++ would be increased.
ROMK contributes to the positive charge in the distal tubule lumen. If the lumen charge is too negative, Ca++ won't be driven to leave the lumen.
What does NKCC2 sometimes transport instead of K+?
What percentage of filtered Mg++ is reabsorbed in the the ascending tubule?
What percentage of synthesized ammonia is reabsorbed in the thick ascending limb?
How does ascending limb dysfunction lead to hypokalemia and alkalosis?
If NaCl isn't absorbed in thick ascending limb, less water will be absorbed from the distal convoluted tubule.
Reduced ECF + increased distal tubule flow -> renin release -> aldosterone.
Aldosterone will increase H+ and K+ secretion -> hypokalemia and alkalosis.
(Ascending limb dysfunction will also lead to reduced Ca++ reabsorption.)
What is the tonicity (high or low) of fluid entering the distal convoluted tubule?
Low -it has been diluted by the powerful transporters.
What approximate levels of Na+, K+, NH4+, HCO3-, Ca++, and Mg++ entering the distal convoluted tubule? (normally)
Na+: about 10% of filtered Na+ remains.
K+ and NH4+: very low.
HCO3-: very low.
Ca++ and Mg++: moderate
How is Na+ reabsorbed in the distal convoluted tubule?
How is this gradient established?
Apical Na+/Cl- cotransport, driven by basolateral Na+ pump.
What class of drugs inhibits Na+ reabsorption in the distal convoluted tubule? What's the molecular target?
Thiazide diuretics, by inhibiting the Na+/Cl- cotransporter.
What transporter is used for Mg2++ reabsorption?
What creates the gradient that drives this?
TRPM6 is the apical transporter. (the basolateral transporter is unknown?)
This is driven by + charge in the lumen, created by K+ leak channels (Kv1.1 -probably not important.)
Where is Mg2++ mostly absorbed?
DCT1 and DCT2...
What signaling molecule promotes Mg++ reabsorption?
What transporter is used for Ca++ reabsorption?
What are 2 hormones that promote the expression of this transporter?
PTH and 1,25-(OH)2-D3 (activated vitamin D) promote TRPV5 expression, and thus Ca++ reabsorption.
What is the tonicity and pH of fluid leaving the distal convoluted?
Dilute and acidic.
How does the collecting duct get the last bit of sodium out of the filtrate?
How is this regulated?
ENaC brings Na+ in from the lumen. The concentration is made by the Na+/K+ ATPase on the basolateral membrane.
Aldosterone promotes ENaC expression on the membrane.
to be continued
Review: What's the syndrome with constituitively active ENaC?
Liddle's syndrome. Too much Na+ reabsorbed in collecting ducts -> hypervolemia, K+ wasting, alkalosis.
Which cells in the collecting duct transport H+?
How do intercalated cells transport H+?
H+/K+ ATPase and H+ ATPase both pump protons out the apical membrane
The protons come from CO2 + H2O... bicarb is moved into blood in exchange for Cl-.
Urea... is an important solute in the medulla that drives H2O reabsorption from the collecting duct.
How does aldosterone promote H+ secretion, and at high levels cause alkalosis?
ENaC mediated Na+ reabsorption leaves a negative charge in the lumen that drives proton secretion/excretion.