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).