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 does 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 like SGLT, Na+ amino acid, Na+ phosphate, Na+ citrate and Na+ lactate which are involved in the absorption of Na+, glucose, amino acids, phosphate, citrate and lactate respectively along with Na+ as a secondary active transport mechanism using energy derived from the Na+ gradient maintained by Na+K+ ATPase pump. HCO3- absorption occurs in an indirect way via CO2 intermediate and Na+H+ pump. Na+ H+ countertransport mechanism on the luminal membrane transports Na+ into the cell and H+ out of the cell, which combines with HCO3- in the lumen to form CO2, which enters the cell and converts back to HCO3-.

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

PTH inhibits 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 thus rise after action of PTH on the PCT cells. This receptor is defective in pseudohypoparathyroidism.

Only free Ca++ that is 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 only 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 Na+ gradient. A portion of the absorbed K+ diffuses back into the lumen, hence the three ion transporter becomes electrogenic, making the luminal side more positive. Ca++ absorption occurs parallel to Na+ absorption in the thick ascending limb. Ca++ is absorbed along a paracellular route and is dependent on the “lumen positive potential difference”. Drugs like loop diuretics that block the Na+K+2Cl- cotransporter will also indirectly inhibit Ca++ absorption and have the potential to cause hypocalcemia.

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

The thick ascending limb is the site where majority of filtered Mg++ is absorbed. It is dependent on the “lumen positive potential difference” created by the Na+K+2Cl- transporter. Loop diuretics by blocking the Na+K+2Cl- transporter have the potential to induce hypomagnesemia.

The thick ascending limb is impermeable to water. As a result, NaCl is absorbed while water is not absorbed, 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. As 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 has two special cell types - principal cells and alpha - intercalated cells. The principal cells are involved in Na+ and water reabsorption and K+ secretion. The 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 the principal cells is dependent on the electrochemical gradient for K+ as K+ simply diffuses down its concentration gradient. Higher the intracellular K+ concentration, more will be the K+ excretion. Any factor that increases Na+ reabsorption will lead to increased K+ secretion e.g. aldosterone, high Na+ diet etc.

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

Water reabsorption by the late distal tubule and collecting ducts is dependent 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 does 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 like SGLT, Na+ amino acid, Na+ phosphate, Na+ citrate and Na+ lactate which are involved in the absorption of Na+, glucose, amino acids, phosphate, citrate and lactate respectively along with Na+ as a secondary active transport mechanism using energy derived from the Na+ gradient maintained by Na+K+ ATPase pump. HCO3- absorption occurs in an indirect way via CO2 intermediate and Na+H+ pump. Na+ H+ countertransport mechanism on the luminal membrane transports Na+ into the cell and H+ out of the cell, which combines with HCO3- in the lumen to form CO2, which enters the cell and converts back to HCO3-.

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

PTH inhibits 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 thus rise after action of PTH on the PCT cells. This receptor is defective in pseudohypoparathyroidism.

Only free Ca++ that is 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 only 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 Na+ gradient. A portion of the absorbed K+ diffuses back into the lumen, hence the three ion transporter becomes electrogenic, making the luminal side more positive. Ca++ absorption occurs parallel to Na+ absorption in the thick ascending limb. Ca++ is absorbed along a paracellular route and is dependent on the “lumen positive potential difference”. Drugs like loop diuretics that block the Na+K+2Cl- cotransporter will also indirectly inhibit Ca++ absorption and have the potential to cause hypocalcemia.

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

The thick ascending limb is the site where majority of filtered Mg++ is absorbed. It is dependent on the “lumen positive potential difference” created by the Na+K+2Cl- transporter. Loop diuretics by blocking the Na+K+2Cl- transporter have the potential to induce hypomagnesemia.

The thick ascending limb is impermeable to water. As a result, NaCl is absorbed while water is not absorbed, 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. As 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 has two special cell types - principal cells and alpha - intercalated cells. The principal cells are involved in Na+ and water reabsorption and K+ secretion. The 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 the principal cells is dependent on the electrochemical gradient for K+ as K+ simply diffuses down its concentration gradient. Higher the intracellular K+ concentration, more will be the K+ excretion. Any factor that increases Na+ reabsorption will lead to increased K+ secretion e.g. aldosterone, high Na+ diet etc.

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

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