Renal Tubular Function Flashcards
How is the proximal tubule divided?
- The first 60% is the proximal convoluted tubule.
- The last 40% is the proximal straight tubule.
In which layer of the kidney is the proximal tubule?
The renal cortex.
What lines the surface of the proximal convoluted tubule?
Microvilli, forming a brush border.
How is directional ion movement controlled in the proximal convoluted tubule?
The ion channels, exchangers, cotransporters (secondary active) and pumps (primary active) are selectively distributed on the apical and basolateral membranes.
List the primary routes of transport for ions and water.
1 - Transcellular (through cells).
2 - Paracellular (between cells).
If the proximal tubule is water permeable, what can be said about the tonicity of the interstitial space?
The interstitial space is ~isotonic with the filtrate passing through it.
How much water is reabsorbed by the end of the proximal convoluted tubule?
~70%.
List the substances for which absorption in the proximal convoluted tubule is driven by movement of Na+.
1 - Water.
2 - Glucose
3 - Amino acids.
How is Na+ extruded from an endothelial cell in the proximal convoluted tubule?
Via the Na+/K+ ATPase on the basolateral membrane.
Through which channels does water pass to cross cell membranes in the proximal tubule?
Aquaporin 1.
List 2 molecules that are not reabsorbed along the proximal tubule.
1 - Inulin (a polysaccharide).
2 - Creatinine.
List 2 molecules that are reabsorbed along the proximal tubule to a lesser extent than water.
How will the concentration of these molecules change along the proximal tubule?
1 - Urea.
2 - Cl-.
- The concentration of these molecules at the end of the tubule will be higher than at the start.
List 2 molecules that are reabsorbed along the proximal tubule to approximately the same extent as water.
1 - Na+.
2 - K+.
- The concentration of these molecules at the end of the tubule will be the same as that at the start.
List 3 molecules that are reabsorbed along the proximal tubule to a greater extent than water.
1 - HCO3-.
2 - Amino acids.
3 - Glucose.
- The concentration of these molecules at the end of the tubule will be lower than that at the start.
Describe the process by which glucose is reabsorbed in the proximal tubule.
- The active extrusion of Na + on the basal side of the cell by the Na + K + ATPase generates an electrochemical gradient for Na+ entry into the cell from the tubule, across the apical membrane.
- Na+ enters the cell with glucose via glucose symporters known as SGLT2 in the early proximal tubule and SGLT1 in the late proximal tubule. This creates a gradient for glucose movement out of the cell.
- Glucose exits the cell on the basolateral side of the cell via GLUT2 in the early proximal tubule and GLUT1 in the late proximal tubule.
What is the difference between SGLT2 and SGLT1?
- SGLT2 transports 1 Na+ for each glucose, whereas SGLT1 transports 2 Na+ for each glucose.
- SGLT2 transporters are low affinity, but high capacity.
- SGLT1 transporters are high affinity, but low capacity.
Why is SGLT2 found in the early proximal tubule whereas SGLT1 is found in the late proximal tubule?
- Early in the proximal tubule, the concentration of glucose in the tubule lumen is higher than in the late tubule.
- Therefore less energy is required to move glucose up its concentration gradient into the cell at the early tubule, as the gradient is shallower.
- Therefore, in the early tubule, 1 Na+ is sufficient to move glucose into the cell using secondary active transport (SGLT2), whereas 2Na+ are required in the late tubule (SGLT1).
What is the maximum transport for glucose in adults?
380 mg min^-1.
What type of drugs are canagliflozin and dapagliflozin?
What is their purpose and how do they work?
- Canagliflozin and dapagliflozin are SGLT2 inhibitors.
- They are used for the treatment of diabetes.
- They work by preventing glucose reabsorption, therefore causing glucosuria and increasing glucose excretion.
List 2 side effects of SGLT 2 inhibitors
1 - Genital yeast and urinary tract infections (UTIs due to stagnant urine).
2 - Polyuria.
What is the plasma amino acid concentration?
2.5-3.5mM.
What is the plasma glucose concentration?
3.9-7.1mM.
How are most amino acids transported from the tubule lumen into the intracellular spaces?
By various cotransporters that use the Na+ gradient (analogous to SGLTs for glucose).
Describe the process by which HCO3- is reabsorbed in the proximal tubule.
1 - H+ ions are pumped out of the epithelial cells by a Na+/H+ exchanger.
2 - In the tubule lumen, H+ and HCO3- form H2CO3.
3 - Carbonic anhydrase converts H2CO3 -> H2O and CO2, which can diffuse freely into the epithelial cells.
4 - Carbonic anhydrase reconverts H2O and CO2 into H2CO3.
5 - H2CO3 dissociates into H+ and HCO3-.
6 - HCO3- exits the cell via HCO3- / Na+ cotransporters on the basolateral membrane, which cotransports 1 HCO3- ion and 3 Na+ ions (both out of the basolateral membrane).
How is a concentration gradient maintained for Na+ entry into epithelial cells?
A Na+/K+ ATPase is present on the basolateral surface of the epithelial cells, which transports 3 Na+ out of the cell for every 2 K+ in.
What is acetazolamide?
What is its purpose and how does it work?
- Acetazolamide is an inhibitor for carbonic anhydrase.
- It is used as a weak diuretic (increases urine production).
- It works by decreasing Na+ and HCO3- reabsorption, which therefore reduces reabsorption of water.
How does acetazolamide affect pH of the urine and blood?
1 - Urine becomes alkaline.
2 - Causes metabolic acidosis.
List 2 conditions that may be treated using acetazolamide.
1 - Glaucoma.
2 - Mountain sickness.
What is the concentration of HCO3- in the filtrate?
25mM.
How does caffeine produce a diuretic effect?
- Caffeine is an adenosine receptor antagonist, and therefore suppresses the sodium-bicarbonate cotransporter.
- By inhibiting Na+ and HCO3- reabsorption, water reabsorption is inhibited, causing diuresis.
Describe the active process by which Cl- is reabsorbed in the proximal tubule.
1 - Cl- is transported into endothelial cells via antiporters for HCO3- and HCOO-.
2 - The Na+/H+ antiporter transports H+ out of the endothelial cell into the lumen in exchange for Na+.
3 - HCOO- in the lumen combines with H+ to form HCOOH, which can freely diffuse into the endothelial cell.
4 - HCOOH dissociates into HCOO- and H+ in the endothelial cell, where HCOO- can be exchanged for more Cl- and H+ can be exchanged for more Na+.
5 - Cl- exits the cell via Cl-/K+ symporters on the basolateral membrane and through Cl- channels.
Describe the passive process by which Cl- is reabsorbed in the proximal tubule.
Where in the proximal convoluted tubule does this happen at the highest rate?
- Cl- diffuses through the paracellular route.
- This happens at the highest rate in the late proximal tubule, as the Cl- concentration is higher.
Why is less Cl- absorbed than Na+ in the early proximal tubule?
Why is this significant for Cl- movement late in the tubule?
- Because Na+ is also required for the absorptions of other solutes.
- This is significant as Cl- concentration will modestly increase down the tubule, driving passive movement of Cl- paracellularly.
How is albumin reabsorbed in the proximal tubule?
1 - Albumin binds to the plasma membrane of the tubule endothelial cells.
2 - It is then endocytosed.
3 - It is then catabolised to its amino acids for recycling in the body.
Where does organic acid and base secretion occur along the tubule?
- Organic acid secretion takes place in the proximal straight tubule.
- Organic base secretion occurs in the proximal convoluted tubule.
List 3 organic anions that are actively secreted in the proximal tubule.
1 - Penicillin.
2 - PAH (used to measure renal function).
3 - Furosemide (a diuretic).
How do organic anions enter the endothelial cells of the proximal tubule for excretion?
Via organic anion transporters (OATs) on the basolateral membrane of the cell.
How do organic anions exit the endothelial cells of the proximal tubule for excretion?
Via multidrug resistance-associated proteins (MRPs).
Describe the process of Na+ reabsorption into renal endothelial cells.
- Down a large electrochemical gradient; Na+ reabsorption is passive (as long as its concentration gradient is maintained).
- However, entry of Na+ is carrier mediated; many other solutes are transported by Na+ symport and antiport.
- Most Na+ entry is via Na+/H+ antiport.
