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Renal Physiology 3Renal Physiology 3
Dr. Bikesh Pandey
Urine formation 2Urine formation 2
Urine FormationUrine Formation
• Results from :
– Glomerular Filtration
– Tubular Reabsorption
– Tubular Secretion
Tubular ReabsorptionTubular Reabsorption
Tubular ReabsorptionTubular Reabsorption
• For reabsorbtion, substance must be
transported :
(1) Across the tubular epithelial membranes
into interstitial fluid
Routes of transportRoutes of transport ::
• Transcellular pathTranscellular path
– Water and solutes can be transported
through cell .
• Paracellular pathParacellular path
– Through the junctional spaces between
the cells
(2) Through the interstitium back into the
blood .
• Ultrafiltration (Bulk Flow)
Tubular ReabsorptionTubular Reabsorption
• Solutes are transported :
– Through the cells (Transcellular route) by:
• Diffusion or
• Active transport
or
– Between the cells (Paracellular route) by:
• Diffusion
• Water is transported through the cells and between the tubular
cells by osmosis.
Reabsorption of GlucoseReabsorption of Glucose
• By “Secondary active transport” in PCT.
• By “Sodium – Glucose co-transport ”
• Sodium-potassium pump transports sodium from the interior of
the cell across the basolateral membrane.
• It creates a low intracellular sodium concentration and a
negative intracellular electrical potential.
• This drives sodium to inside the cell, which is co-transported
with glucose.
• After entry into the cell, glucose exit across the basolateral
membranes by facilitated diffusion.
Reabsorption of GlucoseReabsorption of Glucose
Reabsorption of Amino AcidReabsorption of Amino Acid
• With the same mechanism as “Glucose”
i.e. by sodium co-transport.
Reabsorption of ProteinsReabsorption of Proteins
• PCT, reabsorbs large proteins by Pinocytosis.
• Once inside the cell, the protein is digested into
its constituent amino acids, which are
reabsorbed through the basolateral membrane
into the interstitial fluid.
Pinocytosis for proteinsPinocytosis for proteins
Reabsorption of SodiumReabsorption of Sodium
• Sodium-potassium pump transports sodium from the
interior of the cell across the basolateral membrane.
• It creates a low intracellular sodium concentration and
a negative intracellular electrical potential.
• It causes:
– Sodium ions to diffuse into the cell.
– Activation of sodium co-transport with many different
substances.
Reabsorption of SodiumReabsorption of Sodium
Reabsorption of SodiumReabsorption of Sodium
Involves three steps:Involves three steps:
1. Na+ is transported into the cell down
an electrochemical gradient
established by the Na+/K+ pump on
the basolateral side of the
membrane.
2. Sodium is transported across the basolateral membrane by the
sodium-potassium ATPase pump.
3. Sodium is reabsorbed from the interstitial fluid into the
peritubular capillaries by ultrafiltration.
Reabsorption of SodiumReabsorption of Sodium
• It is also antiported with “Secretion of H+”
Water ReabsorptionWater Reabsorption
• When solutes are transported out of the tubule, it increases the
osmotic pressure on the other side.
• And this drags the water to the hyperosmolar side.
• PCT is highly permeable to water.
• Distal parts of the nephron, like; loop of Henle to the collecting
tubule, become less permeable to water and solutes.
• However, Anti-Diuretic Hormone (ADH) greatly increases the
water permeability in the distal and collecting tubules.
Water ReabsorptionWater Reabsorption
• Thus, water movement across the tubular epithelium can occur
only if the membrane is permeable to water, no matter how
large the osmotic gradient.
• In the proximal tubule, the water permeability is always high,
and water is reabsorbed as rapidly as the solutes.
• In the ascending loop of Henle, water permeability is always
low, so that almost no water is reabsorbed,despite a large
osmotic gradient.
• Water permeability in the last parts of the tubules—the distal
tubules, collecting tubules, and collecting ducts—can be high or
low, depending on the presence or absence of ADH.
Water ReabsorptionWater Reabsorption
Solvent dragSolvent drag
• As water moves across the tight junctions
by osmosis, it can also carry with it some
of the solutes, & this process is referred to
as solvent drag.
Reabsorption of ChlorideReabsorption of Chloride
Happens in three different manners:
• By Secondary active transport
– Co-transport of chloride with sodium across the luminal
membrane.
• By concentration gradient
– When water is reabsorbed from the tubule by osmosis, it
concentrates the chloride ions in the tubular lumen & thus
causes diffusion of Cl –
• By electrical gradient
– When Na+ is reabsorbed it leaves the inside of the lumen
negatively charged, compared with the interstitial fluid.
– This causes chloride ions to diffuse passively through the
Reabsorption of UreaReabsorption of Urea
• Only half of the urea that is filtered is reabsorbed,
remaining urea passes into the urine.
• Reabsorption happens in following manners:
– By concentration gradient
• When water is reabsorbed from the tubule by osmosis, it
concentrates the Urea in the tubular lumen & thus causes diffusion.
– By urea transporters
• We know urea is not permeable in the tubule as readily as water.
• In some parts of the nephron, especially the inner medullary
collecting duct, passive urea reabsorption is facilitated by specific
urea transporters.
Reabsorption of CreatinineReabsorption of Creatinine
• Creatinine, is a large molecule and is
essentially impermeant to the tubular
membrane.
• Therefore, almost none of the creatinine
that is filtered is reabsorbed, so that
virtually all the creatinine filtered by the
glomerulus is excreted in the urine.
Transport MaximumTransport Maximum
• For substances that are actively transported,
there is a limit to the rate at which the solute
can be transported, called as TransportTransport
maximummaximum.
• This limit is due to saturation of the specific
transport systems involved when the amount of
solute delivered to the tubule (tubular load)
exceeds the capacity of the carrier proteins.
Transport MaximumTransport Maximum
ExampleExample
• We know that Normally, all the filtered glucose
is reabsorbed in PCT
• So glucose does not appear in the urine
• However, when the filtered load exceeds the
capability of the tubules to reabsorb glucose,
urinary excretion of glucose does occur.
Transport MaximumTransport Maximum
ExampleExample
• Transport maximum for glucose averages about 375
mg/min.
• Normally Filtered load of glucose is only about 125
mg/min (GFR X plasma glucose = 125 ml/min X 1
mg/ml).
• With large increases in GFR and/or plasma glucose
concentration that increase the filtered load of glucose
above 375 mg/ min, the excess glucose filtered is not
reabsorbed and passes into the urine.
Transport MaximumTransport Maximum
ExampleExample
• When the plasma glucose concentration is 100
mg/100 mL and the filtered load is at its normal level,
125 mg/min, there is no loss of glucose in the urine.
• However, when the plasma concentration of glucose
rises above about 200 mg/100 ml, increasing the
filtered load to about 250 mg/min, a small amount of
glucose begins to appear in the urine.
• This point is termed the threshold for glucose.
Transport MaximumTransport Maximum
ExampleExample
• Note that this appearance of glucose in the urine (at the
threshold) occurs before the transport maximum is reached.
• Reason for the difference between threshold and transport
maximum is that not all nephrons have the same transport
maximum for glucose, and some of the nephrons excrete
glucose before others have reached their transport maximum.
• The overall transport maximum for the kidneys, which is
normally about 375 mg/min, is reached when all nephrons have
reached their maximal capacity to reabsorb glucose.
Transport Maximum for someTransport Maximum for some
substancessubstances
Na+ Reabsorption in PCT does Not Exhibit a Transport MaximumNa+ Reabsorption in PCT does Not Exhibit a Transport Maximum
• The maximum transport capacity of the basolateral sodium-
potassium ATPase pump is usually far greater than the actual
rate of net sodium reabsorption.
• Other factors limit the reabsorption rate besides the maximum
rate of active transport.
• The “Tight Junction” of PCT despite the name is not
impermeable to sodium.
• So that significant amount of sodium transported out of the cell
leaks back.
Transport MaximumTransport Maximum
Transport MaximumTransport Maximum
Na+ Reabsorption in PCT does Not Exhibit a TransportNa+ Reabsorption in PCT does Not Exhibit a Transport
MaximumMaximum
• In the more distal parts of the nephron, the epithelial
cells have much tighter junctions and transport much
smaller amounts of sodium.
• In these segments, sodium reabsorption exhibits a
transport maximum similar to that for other actively
transported substances.
• Furthermore, this transport maximum can be
increased in response to certain hormones, such as
aldosterone.
To Be Continued……To Be Continued……

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Renal physiology 3

  • 1. Renal Physiology 3Renal Physiology 3 Dr. Bikesh Pandey
  • 3. Urine FormationUrine Formation • Results from : – Glomerular Filtration – Tubular Reabsorption – Tubular Secretion
  • 4.
  • 6. Tubular ReabsorptionTubular Reabsorption • For reabsorbtion, substance must be transported : (1) Across the tubular epithelial membranes into interstitial fluid Routes of transportRoutes of transport :: • Transcellular pathTranscellular path – Water and solutes can be transported through cell . • Paracellular pathParacellular path – Through the junctional spaces between the cells (2) Through the interstitium back into the blood . • Ultrafiltration (Bulk Flow)
  • 7. Tubular ReabsorptionTubular Reabsorption • Solutes are transported : – Through the cells (Transcellular route) by: • Diffusion or • Active transport or – Between the cells (Paracellular route) by: • Diffusion • Water is transported through the cells and between the tubular cells by osmosis.
  • 8. Reabsorption of GlucoseReabsorption of Glucose • By “Secondary active transport” in PCT. • By “Sodium – Glucose co-transport ” • Sodium-potassium pump transports sodium from the interior of the cell across the basolateral membrane. • It creates a low intracellular sodium concentration and a negative intracellular electrical potential. • This drives sodium to inside the cell, which is co-transported with glucose. • After entry into the cell, glucose exit across the basolateral membranes by facilitated diffusion.
  • 10. Reabsorption of Amino AcidReabsorption of Amino Acid • With the same mechanism as “Glucose” i.e. by sodium co-transport.
  • 11. Reabsorption of ProteinsReabsorption of Proteins • PCT, reabsorbs large proteins by Pinocytosis. • Once inside the cell, the protein is digested into its constituent amino acids, which are reabsorbed through the basolateral membrane into the interstitial fluid.
  • 13. Reabsorption of SodiumReabsorption of Sodium • Sodium-potassium pump transports sodium from the interior of the cell across the basolateral membrane. • It creates a low intracellular sodium concentration and a negative intracellular electrical potential. • It causes: – Sodium ions to diffuse into the cell. – Activation of sodium co-transport with many different substances.
  • 15. Reabsorption of SodiumReabsorption of Sodium Involves three steps:Involves three steps: 1. Na+ is transported into the cell down an electrochemical gradient established by the Na+/K+ pump on the basolateral side of the membrane. 2. Sodium is transported across the basolateral membrane by the sodium-potassium ATPase pump. 3. Sodium is reabsorbed from the interstitial fluid into the peritubular capillaries by ultrafiltration.
  • 16. Reabsorption of SodiumReabsorption of Sodium • It is also antiported with “Secretion of H+”
  • 17. Water ReabsorptionWater Reabsorption • When solutes are transported out of the tubule, it increases the osmotic pressure on the other side. • And this drags the water to the hyperosmolar side. • PCT is highly permeable to water. • Distal parts of the nephron, like; loop of Henle to the collecting tubule, become less permeable to water and solutes. • However, Anti-Diuretic Hormone (ADH) greatly increases the water permeability in the distal and collecting tubules.
  • 18. Water ReabsorptionWater Reabsorption • Thus, water movement across the tubular epithelium can occur only if the membrane is permeable to water, no matter how large the osmotic gradient. • In the proximal tubule, the water permeability is always high, and water is reabsorbed as rapidly as the solutes. • In the ascending loop of Henle, water permeability is always low, so that almost no water is reabsorbed,despite a large osmotic gradient. • Water permeability in the last parts of the tubules—the distal tubules, collecting tubules, and collecting ducts—can be high or low, depending on the presence or absence of ADH.
  • 19. Water ReabsorptionWater Reabsorption Solvent dragSolvent drag • As water moves across the tight junctions by osmosis, it can also carry with it some of the solutes, & this process is referred to as solvent drag.
  • 20. Reabsorption of ChlorideReabsorption of Chloride Happens in three different manners: • By Secondary active transport – Co-transport of chloride with sodium across the luminal membrane. • By concentration gradient – When water is reabsorbed from the tubule by osmosis, it concentrates the chloride ions in the tubular lumen & thus causes diffusion of Cl – • By electrical gradient – When Na+ is reabsorbed it leaves the inside of the lumen negatively charged, compared with the interstitial fluid. – This causes chloride ions to diffuse passively through the
  • 21. Reabsorption of UreaReabsorption of Urea • Only half of the urea that is filtered is reabsorbed, remaining urea passes into the urine. • Reabsorption happens in following manners: – By concentration gradient • When water is reabsorbed from the tubule by osmosis, it concentrates the Urea in the tubular lumen & thus causes diffusion. – By urea transporters • We know urea is not permeable in the tubule as readily as water. • In some parts of the nephron, especially the inner medullary collecting duct, passive urea reabsorption is facilitated by specific urea transporters.
  • 22.
  • 23. Reabsorption of CreatinineReabsorption of Creatinine • Creatinine, is a large molecule and is essentially impermeant to the tubular membrane. • Therefore, almost none of the creatinine that is filtered is reabsorbed, so that virtually all the creatinine filtered by the glomerulus is excreted in the urine.
  • 24. Transport MaximumTransport Maximum • For substances that are actively transported, there is a limit to the rate at which the solute can be transported, called as TransportTransport maximummaximum. • This limit is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule (tubular load) exceeds the capacity of the carrier proteins.
  • 25. Transport MaximumTransport Maximum ExampleExample • We know that Normally, all the filtered glucose is reabsorbed in PCT • So glucose does not appear in the urine • However, when the filtered load exceeds the capability of the tubules to reabsorb glucose, urinary excretion of glucose does occur.
  • 26. Transport MaximumTransport Maximum ExampleExample • Transport maximum for glucose averages about 375 mg/min. • Normally Filtered load of glucose is only about 125 mg/min (GFR X plasma glucose = 125 ml/min X 1 mg/ml). • With large increases in GFR and/or plasma glucose concentration that increase the filtered load of glucose above 375 mg/ min, the excess glucose filtered is not reabsorbed and passes into the urine.
  • 27. Transport MaximumTransport Maximum ExampleExample • When the plasma glucose concentration is 100 mg/100 mL and the filtered load is at its normal level, 125 mg/min, there is no loss of glucose in the urine. • However, when the plasma concentration of glucose rises above about 200 mg/100 ml, increasing the filtered load to about 250 mg/min, a small amount of glucose begins to appear in the urine. • This point is termed the threshold for glucose.
  • 28. Transport MaximumTransport Maximum ExampleExample • Note that this appearance of glucose in the urine (at the threshold) occurs before the transport maximum is reached. • Reason for the difference between threshold and transport maximum is that not all nephrons have the same transport maximum for glucose, and some of the nephrons excrete glucose before others have reached their transport maximum. • The overall transport maximum for the kidneys, which is normally about 375 mg/min, is reached when all nephrons have reached their maximal capacity to reabsorb glucose.
  • 29.
  • 30. Transport Maximum for someTransport Maximum for some substancessubstances
  • 31. Na+ Reabsorption in PCT does Not Exhibit a Transport MaximumNa+ Reabsorption in PCT does Not Exhibit a Transport Maximum • The maximum transport capacity of the basolateral sodium- potassium ATPase pump is usually far greater than the actual rate of net sodium reabsorption. • Other factors limit the reabsorption rate besides the maximum rate of active transport. • The “Tight Junction” of PCT despite the name is not impermeable to sodium. • So that significant amount of sodium transported out of the cell leaks back. Transport MaximumTransport Maximum
  • 32. Transport MaximumTransport Maximum Na+ Reabsorption in PCT does Not Exhibit a TransportNa+ Reabsorption in PCT does Not Exhibit a Transport MaximumMaximum • In the more distal parts of the nephron, the epithelial cells have much tighter junctions and transport much smaller amounts of sodium. • In these segments, sodium reabsorption exhibits a transport maximum similar to that for other actively transported substances. • Furthermore, this transport maximum can be increased in response to certain hormones, such as aldosterone.
  • 33. To Be Continued……To Be Continued……