Renal tubules | Renal and urinary system | Physiology

Renal tubules

Renal tubules and their role in homeostasis

Proximal convoluted tubule (PCT): It reabsorbs close to 70% of the filtered Na+. The early PCT performs isosmotic reabsorption of Na+ along with HCO3-, phosphate, glucose, and amino acids. The late PCT absorbs Na+ along with Cl- (not HCO3-). The luminal membrane has several cotransport mechanisms (SGLT, Na±amino acid, Na±phosphate, Na±citrate, and Na±lactate) that absorb Na+, glucose, amino acids, phosphate, citrate, and lactate, respectively. These are secondary active transport processes that use energy from the Na+ gradient maintained by the Na+K+ ATPase pump.

HCO3- absorption occurs indirectly via a CO2 intermediate and the Na+H+ pump. The Na+H+ countertransport mechanism on the luminal membrane transports Na+ into the cell and H+ out of the cell. In the lumen, H+ combines with HCO3- to form CO2, which enters the cell and is converted back to HCO3-.

The late PCT has a luminal Na+H+ exchanger and a Cl–formate ion exchanger, which together result in net absorption of Na+ and Cl- into the cell. Na+ and Cl- also move through paracellular spaces and are absorbed from the lumen into the bloodstream.

PTH inhibits the Na±phosphate cotransporter in the PCT, causing phosphaturia. PTH acts through a Gs protein-linked receptor and activates adenylyl cyclase, leading to increased intracellular cAMP, which is then excreted in urine. Urinary cAMP levels therefore rise after PTH acts on PCT cells. This receptor is defective in pseudohypoparathyroidism.

Only free Ca++ (not bound to plasma proteins) can be filtered at the glomerulus. Ca++ reabsorption is coupled to Na+ absorption in the PCT.
Loop of Henle: The thin descending limb is permeable to water, NaCl, and urea, while the thick ascending limb is permeable to NaCl, moderately permeable to urea, but impermeable to water.

The thick ascending limb reabsorbs 25% of Na+. The Na+K+2Cl- cotransporter (NKCC) moves 1 Na+, 1 K+, and 2 Cl- ions into the cells using energy derived from the Na+ gradient. A portion of the absorbed K+ diffuses back into the lumen, so the transporter becomes electrogenic and makes the luminal side more positive. Ca++ absorption occurs parallel to Na+ absorption in the thick ascending limb. Ca++ is absorbed via a paracellular route and depends on the “lumen positive potential difference.” Drugs such as loop diuretics that block the Na+K+2Cl- cotransporter will also indirectly inhibit Ca++ absorption and can cause hypocalcemia.

Loop diuretics block the Cl- binding site on the Na+K+2Cl- transporter and can cause hyponatremia and hypokalemia.

The thick ascending limb is the site where the majority of filtered Mg++ is absorbed. This absorption depends on the “lumen positive potential difference” created by the Na+K+2Cl- transporter. By blocking the Na+K+2Cl- transporter, loop diuretics can induce hypomagnesemia.

The thick ascending limb is impermeable to water. As a result, NaCl is absorbed while water is not, leading to hypotonicity of the luminal fluid.
Distal tubule and collecting duct: The Na+Cl- cotransporter in the luminal membrane of the early distal tubule absorbs Na+ and, along with it, Cl- into the cell. Because this segment is also impermeable to water, it dilutes the tubular fluid even further. Thiazide diuretics block the Na+Cl- cotransporter by binding to the Cl- site.

The late distal tubule and collecting ducts have two special cell types: principal cells and alpha-intercalated cells. Principal cells are involved in Na+ and water reabsorption and K+ secretion. Alpha-intercalated cells are involved in K+ reabsorption and H+ secretion. H+K+ATPase on the luminal membrane of the intercalated cell moves K+ into the cell while H+ moves from the cell into the lumen.

K+ secretion by principal cells depends on the electrochemical gradient for K+, because K+ diffuses down its concentration gradient. The higher the intracellular K+ concentration, the greater the K+ excretion. Any factor that increases Na+ reabsorption will increase K+ secretion (e.g., aldosterone, high Na+ diet).

In the distal tubule, Ca++ absorption is not dependent on Na+ absorption. The distal tubule regulates Ca++ absorption under the action of PTH via cAMP. PTH promotes hypocalciuria and phosphaturia.

The luminal membrane of principal cells has ENaC channels (epithelial sodium channels) through which Na+ enters the cell down its electrochemical gradient (so no energy is required). Aldosterone increases transcription of ENaC channel proteins, leading to increased Na+ absorption. K+sparing diuretics inhibit Na+ absorption and K+ secretion by principal cells, with the potential to cause hyperkalemia.

Water reabsorption by the late distal tubule and collecting ducts depends on ADH.

Renal tubules

Renal tubules and their role in homeostasis

Proximal convoluted tubule (PCT): It reabsorbs close to 70% of the filtered Na+. The early PCT performs isosmotic reabsorption of Na+ along with HCO3-, phosphate, glucose, and amino acids. The late PCT absorbs Na+ along with Cl- (not HCO3-). The luminal membrane has several cotransport mechanisms (SGLT, Na±amino acid, Na±phosphate, Na±citrate, and Na±lactate) that absorb Na+, glucose, amino acids, phosphate, citrate, and lactate, respectively. These are secondary active transport processes that use energy from the Na+ gradient maintained by the Na+K+ ATPase pump.

HCO3- absorption occurs indirectly via a CO2 intermediate and the Na+H+ pump. The Na+H+ countertransport mechanism on the luminal membrane transports Na+ into the cell and H+ out of the cell. In the lumen, H+ combines with HCO3- to form CO2, which enters the cell and is converted back to HCO3-.

The late PCT has a luminal Na+H+ exchanger and a Cl–formate ion exchanger, which together result in net absorption of Na+ and Cl- into the cell. Na+ and Cl- also move through paracellular spaces and are absorbed from the lumen into the bloodstream.

PTH inhibits the Na±phosphate cotransporter in the PCT, causing phosphaturia. PTH acts through a Gs protein-linked receptor and activates adenylyl cyclase, leading to increased intracellular cAMP, which is then excreted in urine. Urinary cAMP levels therefore rise after PTH acts on PCT cells. This receptor is defective in pseudohypoparathyroidism.

Only free Ca++ (not bound to plasma proteins) can be filtered at the glomerulus. Ca++ reabsorption is coupled to Na+ absorption in the PCT.
Loop of Henle: The thin descending limb is permeable to water, NaCl, and urea, while the thick ascending limb is permeable to NaCl, moderately permeable to urea, but impermeable to water.

The thick ascending limb reabsorbs 25% of Na+. The Na+K+2Cl- cotransporter (NKCC) moves 1 Na+, 1 K+, and 2 Cl- ions into the cells using energy derived from the Na+ gradient. A portion of the absorbed K+ diffuses back into the lumen, so the transporter becomes electrogenic and makes the luminal side more positive. Ca++ absorption occurs parallel to Na+ absorption in the thick ascending limb. Ca++ is absorbed via a paracellular route and depends on the “lumen positive potential difference.” Drugs such as loop diuretics that block the Na+K+2Cl- cotransporter will also indirectly inhibit Ca++ absorption and can cause hypocalcemia.

Loop diuretics block the Cl- binding site on the Na+K+2Cl- transporter and can cause hyponatremia and hypokalemia.

The thick ascending limb is the site where the majority of filtered Mg++ is absorbed. This absorption depends on the “lumen positive potential difference” created by the Na+K+2Cl- transporter. By blocking the Na+K+2Cl- transporter, loop diuretics can induce hypomagnesemia.

The thick ascending limb is impermeable to water. As a result, NaCl is absorbed while water is not, leading to hypotonicity of the luminal fluid.
Distal tubule and collecting duct: The Na+Cl- cotransporter in the luminal membrane of the early distal tubule absorbs Na+ and, along with it, Cl- into the cell. Because this segment is also impermeable to water, it dilutes the tubular fluid even further. Thiazide diuretics block the Na+Cl- cotransporter by binding to the Cl- site.

The late distal tubule and collecting ducts have two special cell types: principal cells and alpha-intercalated cells. Principal cells are involved in Na+ and water reabsorption and K+ secretion. Alpha-intercalated cells are involved in K+ reabsorption and H+ secretion. H+K+ATPase on the luminal membrane of the intercalated cell moves K+ into the cell while H+ moves from the cell into the lumen.

K+ secretion by principal cells depends on the electrochemical gradient for K+, because K+ diffuses down its concentration gradient. The higher the intracellular K+ concentration, the greater the K+ excretion. Any factor that increases Na+ reabsorption will increase K+ secretion (e.g., aldosterone, high Na+ diet).

In the distal tubule, Ca++ absorption is not dependent on Na+ absorption. The distal tubule regulates Ca++ absorption under the action of PTH via cAMP. PTH promotes hypocalciuria and phosphaturia.

The luminal membrane of principal cells has ENaC channels (epithelial sodium channels) through which Na+ enters the cell down its electrochemical gradient (so no energy is required). Aldosterone increases transcription of ENaC channel proteins, leading to increased Na+ absorption. K+sparing diuretics inhibit Na+ absorption and K+ secretion by principal cells, with the potential to cause hyperkalemia.

Water reabsorption by the late distal tubule and collecting ducts depends on ADH.