Proximal tubule Flashcards
Where is the proximal tubule located?
In the cortex
What are the two parts that form the proximal tubule?
Convoluted (first 60%)
Straight (last 40%)
What forms the brush border and what is its function?
Formed by microvilli creating a large SA to form the major site of reabsorption.
What substances are absorbed in the proximal tubule and by how much?
Water - 70% Na - 70% K - 80% Ca - 65% AA - 100% Glucose - 100% Urea - 50% Hco3 - 90%
What substances are secreted in the proximal tubule?
Uric acid
Organic acids / drugs
What is primary active transport?
Generates a gradient due to its movement e.g. Na/K ATPase
What is secondary active transport?
Movement of substances using a gradient generated by primary transport.
How can ions move?
Transcellularly or paracellularly through channels, pumps or cotransporters
How does Na move in the proximal tubule?
Na/K ATPase produces a gradient by tranporting Na out. Na moves DOWN its electrochemical gradient to drive the movement of other substances.
Where is Na/K ATPase located?
On the basolateral membrane
How is water reabsorbed?
Movement of water follows the movement of Na as it creates an osmotic gradient both trans and paracellular.
The filtrate remains isotonic with plasma and interstitial fluid as the tubule is permeable to water.
Water moves through AQP1 channels on the apical membrane
or
Moves paracellular due to outward hydrostatic and osmotic forces.
How is glucose reabsorbed?
Sodium-glucose linked transporter:
In the early stages 90% of glucose uses low affinity, high capacity SGLT2 on apical, coupled with GLUT2 on basal.
As the conc falls along the tubule it is harder to move and requires more energy so uses a high affinity, low capacity SGLT1 on apical, coupled with GLUT1 in basal. SGLT1 uses 2xNa to drive movement of glucose.
What is the Tm of glucose? What happens once Tm is reached?
380mg.min.
Glucose will pass into the urine
What is the concentration of glucose on entering the tubule?
Equal to plasma concentration as it is freely filtered.
Is glucose absorbed faster or slower than water?
Glucose is absorbed FASTER so the concentration FALLS along the tubule, making reabsorption more difficult.
Why might a SGLT2 inhibitor be used?
Caues glucosuria to reduce blood glucose levels in DM.
But increases risk of UTI
How are AA reabsorbed? Are they Tm limited?
AA are cotransported with Na or via H gradient. Tm limited.
What is the plasma concentration of AA?
2.5-3.5mM
Are AA absorbed faster or slower than water?
FASTER - concentration falls along the tubule
How is Hco3 reabsorbed in the tubule?
There is 25mM in the filtrate. 90% is reabsorbed in proximal.
H is secreted into the tubule via Na-H exchanger allowing Hco3 to from H2O and CO2 via Carbonic anhydrase. H2O and CO2 can cross the membrane where they redissociate.
As Hco3 moves down its gradient it facilitates Na movement up its gradient for reabsorption on basal. 3xHco3:Na
Na/K ATPase and K channel maintain the gradients.
What determines the rate of equilibrium of Hco3 reabsorption?
Carbonic Anhydrase
What is Azetazolamide?
A diuretic that inhibits CA to prevent Na and Hco3 reabsorption and therefor reducing H2O reabsorption.
Causes alkaline urine so metabolic acidosis as Hco3 is lost in urine. - Can be used to reverse alkalotic effects of altitude.
Can treat glaucoma and mountain sickness.
How is Cl reabsorbed?
Moves actively and passively.
Antiport exchange with other anions such as Hco3 and Hcoo. The anion can combine with H secreted into the filtrate via Na-H antiporter, which can then cross the membrane and redissociate for a continuous cycle.
As Cl is absorbed slower than water its concentration increases along the tubule, driving passive paracellular and transcellular movement down the gradient.
This movement generates an electrical gradient and 20% Na follows passively in the late PT.
How is albumin reabsorbed?
6% of albumin will enter the filtrate and 100% will be reabsorbed. Via absorptive endocytosis. Albumin binds to sites on the apical membrane that contain megalin and cubilin causing endocytosis. Albumin is the cleaved into AA to be exchanged acorss the BL membrane with Na or H gradient.
What does hyperalbuminuria show?
Glomerular damage
Why are organic anions secreted?
For excretion in the urine. Used to reomve drugs.
Where does acid and base secretion occur?
Acid in the pars recta / straight e.g. penicillin, thiazides, PAH, uric acid
Base in the pars convuluta / convulted e.g. histamine, choline, creatinine, ammonium, guanidine
How is PAH, an anion, secreted?
Transported across BL into the cell in exchange for alphaKG via OAT (organic anion transporter). AplhaKG moves into the cell with Na, to keep a continuous supply for OAT.
PAH is then exchanged on the apical membrane for other anions via MRP.
What happens in the Pars recta?
Na can move via ENAC down its gradient
K is passively reabsorbed paracellularly through tight junctions due to the low extracellular concentration of 4mM. 80-90% occurs this way.
Why are ENAC only present in the late tubule?
It allows secondary active transport to dominate in the early tubule by utilising the Na in the tubule to aid transport. If ENAC was present there would be less Na to aid.
