• The corticopapillary osmotic gradient is the osmotic gradient of the renal interstitium
• It allows the nephrons to adjust the osmolarity of the tubular fluid, and ranges from 300 milliosmoles/liter in the cortex to up to 1200 milliosmoles in the inner medulla

The physiological processes that create the gradient are:

• Medullary countercurrent multiplication
• Urea recycling

Maintenance of the corticopapillary osmotic gradient relies on the vasa recta and countercurrent exchange.

Parts of the nephron:

• Renal corpuscle
• Proximal tubule
• Nephron loop, specify its descending and ascending limbs; recall that the ascending limb is impermeable to water.
• Distal tubule
• Collecting duct
• It is surrounded by the renal interstitium, which comprises tissues and fluids.
• The corticomedullary junction marks where the cortex becomes the medulla
• The proximal and distal tubules lie within the cortex, and the nephron loop lies within the medulla.
• The corticopapillary osmotic gradient (the osmolarity of the interstitium) increases from the cortex to the medulla.

CREATION OF THE CORTICOPAPILLARY OSMOTIC GRADIENT

Medullary countercurrent multiplication

The thick ascending limb actively pumps sodium chloride into the medullary interstitium to create the osmotic gradient:

• Isosmotic tubular fluid enters the descending limb of the nephron loop; its osmolarity is similar to that of blood plasma, 300 milliosmoles/liter.
• Water is passively reabsorbed in the descending limb;
• Consequently, by the time it reaches the bend of the nephron loop, the tubular fluid is hyperosmotic, with osmolarity as high as 1200 milliosmoles/liter; this is because water has left the tubular fluid; solutes have not been added to the tubular fluid.
• The hyperosmotic tubular fluid is “pushed” into the ascending limb by the arrival of new tubular fluid; recall that tubular fluid is constantly flowing through the nephrons.
• Then, as it passes through the ascending limb, sodium chloride is actively reabsorbed from the tubular fluid, which lowers its osmolarity.
• Thus, as it exits the nephron loop, the tubular fluid is hypo-osmotic, at approximately 100 milliosmoles/liter. In other words, the nephron loop has created relatively dilute urine.

Osmolarity of the interstitial fluid:

• Interstitial fluid of the cortex is isosmotic with blood plasma, at 300 milliosmoles/liter
• Osmolarity increases incrementally as we move towards the inner medulla, where, like the tubular fluid, its osmolarity can be as high as 1200 milliosmoles/liter.
• This gradient is created by the continuous reabsorption of water and sodium chloride in the nephron loop:
• Recall that, because water was reabsorbed in the descending limb, the tubular fluid that enters the ascending limb has a very high solute concentration;
• Higher tubular fluid solute concentration leads to increased solute reabsorption, which raises the osmolarity of the medullary interstitium.
• However, as the tubular fluid ascends through the outer medulla and cortex, continuous solute reabsorption reduces its osmolarity.
• Thus, less solutes are available for transport to the interstitium, so its osmolarity decreases as we move superficially.

Urea recycling

Urea is reabsorbed from the medullary collecting ducts and contributes to the corticopapillary osmotic gradient.

• Urea reabsorption relies on the presence of anti-diuretic hormone (ADH, aka, arginine, vasopressin), thus it is most prominent in water depletion states: when circulating ADH levels are high.
• ADH increases water permeability, but has no effect on urea transport.
• As a result of water reabsorption, urea concentration in the tubular fluid increases.
• Then, in the inner medullary collecting duct, indicate that ADH increases both water permeability and urea transport;
• The diffusion of urea into the interstitial fluid increases the osmolarity of the inner medulla, which adds to the corticopapillary osmotic gradient.
• Urea can be secreted into the nephron loop, or, taken up by the vasa recta.

CORTICOPAPILLARY OSMOTIC GRADIENT

• The corticopapillary osmotic gradient is the osmotic gradient of the renal interstitium
• It allows the nephrons to adjust the osmolarity of the tubular fluid, and ranges from 300 milliosmoles/liter in the cortex to up to 1200 milliosmoles in the inner medulla

The physiological processes that create the gradient are:

• Medullary countercurrent multiplication
• Urea recycling

Maintenance of the corticopapillary osmotic gradient relies on the vasa recta and countercurrent exchange.

Parts of the nephron:

• Renal corpuscle
• Proximal tubule
• Nephron loop, specify its descending and ascending limbs; recall that the ascending limb is impermeable to water.
• Distal tubule
• Collecting duct
• It is surrounded by the renal interstitium, which comprises tissues and fluids.
• The corticomedullary junction marks where the cortex becomes the medulla
• The proximal and distal tubules lie within the cortex, and the nephron loop lies within the medulla.
• The corticopapillary osmotic gradient (the osmolarity of the interstitium) increases from the cortex to the medulla.

CREATION OF THE CORTICOPAPILLARY OSMOTIC GRADIENT

Medullary countercurrent multiplication

The thick ascending limb actively pumps sodium chloride into the medullary interstitium to create the osmotic gradient:

• Isosmotic tubular fluid enters the descending limb of the nephron loop; its osmolarity is similar to that of blood plasma, 300 milliosmoles/liter.
• Water is passively reabsorbed in the descending limb;
• Consequently, by the time it reaches the bend of the nephron loop, the tubular fluid is hyperosmotic, with osmolarity as high as 1200 milliosmoles/liter; this is because water has left the tubular fluid; solutes have not been added to the tubular fluid.
• The hyperosmotic tubular fluid is “pushed” into the ascending limb by the arrival of new tubular fluid; recall that tubular fluid is constantly flowing through the nephrons.
• Then, as it passes through the ascending limb, sodium chloride is actively reabsorbed from the tubular fluid, which lowers its osmolarity.
• Thus, as it exits the nephron loop, the tubular fluid is hypo-osmotic, at approximately 100 milliosmoles/liter. In other words, the nephron loop has created relatively dilute urine.

Osmolarity of the interstitial fluid:

• Interstitial fluid of the cortex is isosmotic with blood plasma, at 300 milliosmoles/liter
• Osmolarity increases incrementally as we move towards the inner medulla, where, like the tubular fluid, its osmolarity can be as high as 1200 milliosmoles/liter.
• This gradient is created by the continuous reabsorption of water and sodium chloride in the nephron loop:
• Recall that, because water was reabsorbed in the descending limb, the tubular fluid that enters the ascending limb has a very high solute concentration;
• Higher tubular fluid solute concentration leads to increased solute reabsorption, which raises the osmolarity of the medullary interstitium.
• However, as the tubular fluid ascends through the outer medulla and cortex, continuous solute reabsorption reduces its osmolarity.
• Thus, less solutes are available for transport to the interstitium, so its osmolarity decreases as we move superficially.

Urea recycling

Urea is reabsorbed from the medullary collecting ducts and contributes to the corticopapillary osmotic gradient.

• Urea reabsorption relies on the presence of anti-diuretic hormone (ADH, aka, arginine, vasopressin), thus it is most prominent in water depletion states: when circulating ADH levels are high.
• ADH increases water permeability, but has no effect on urea transport.
• As a result of water reabsorption, urea concentration in the tubular fluid increases.
• Then, in the inner medullary collecting duct, indicate that ADH increases both water permeability and urea transport;
• The diffusion of urea into the interstitial fluid increases the osmolarity of the inner medulla, which adds to the corticopapillary osmotic gradient.
• Urea can be secreted into the nephron loop, or, taken up by the vasa recta.

“Excitable” tissues

• Rely on the potassium concentration gradient across cell membranes to establish resting membrane potentials.
• Excitable tissues include: nerve, skeletal muscle, and cardiac muscle.

Two key forms of potassium balance:

Internal

• Describes potassium distribution between the intra- and extracellular fluid compartments.

External

• Describes the relationship between dietary intake of potassium and its renal excretion.

INTERNAL BALANCE

Homeostasis

• ICF contains 98% of body’s total K+
• ECF contains 2%
• Sodium-potassium ATPase (aka, pump) maintains this homeostatic internal potassium balance.
• Shifts in internal potassium balance can cause cardiac arrhythmia and muscle weakness.

Hypokalemia

Reduced extracellular potassium concentration

• Potassium movement into the cell – intracellular potassium concentration increases and extracellular concentration increases.
• External imbalance can cause hypokalemia from an increased potassium excretion-to-intake ratio.
• Causes of increased intracellular concentration, include hormones, medications, and disease states.
• Specific causes include:
  – Metabolic alkalosis.
  – Diarrhea-induced loss of potassium.
  – Medications
  – Hormones, such as:
  Aldosterone, which acts on the kidney’s reabsorption of potassium (an external balance mechanism).
  Beta-2 adrenergic stimulators and insulin, which drive potassium into the cell (an internal balance mechanism).

Clinical correlation

A rapid correction of hyperkalemia (elevated extracellular potassium) can be achieved with:
– An albuterol inhaler (a beta-2 adrenergic stimulator)
– insulin, which drives potassium from the plasma into the cell (an internal mechanism)
– Kayexylate, which produces a diarrhea-wasting of potassium (an external mechanism)

Hyperkalemia

Increased extracellular potassium concentration

• Potassium movement out of the cell – intracellular potassium concentration decreases and extracellular concentration increases.
• External imbalance can cause hyperkalemia from a reduced potassium excretion-to-intake ratio.
• Specific causes include:
  – Metabolic acidosis.
  – Cell lysis (when the cell bursts, its contents are released) (an internal balance mechanism)
  – Increased ECF osmolarity (water will exit the cell, “dragging” potassium with it) (another internal balance mechanism)
  – Medications, such as:
  ACE Inhibitors, which acts on the kidney’s reabsorption of potassium in the opposite manner as aldosterone (an external balance mechanism).
  Beta-blockers prevent potassium entry into the cell (the opposite of beta-adrenergic stimulators).

Clinical correlation

Chronic kidney failure patients (who can’t excrete potassium) can develop hyperkalemia if they become constipated: they rely on the GI tract for external balance of potassium.

EXTERNAL BALANCE

• Potassium reabsorption and secretion in the distal nephron are hormonally regulated to ensure that renal excretion matches dietary intake, which varies widely both intra- and inter-individually from day to day.
• Potassium is freely filtered within the glomerulus.
• Approximately 67% of the filtered load of potassium is reabsorbed from the proximal tubule.
• 20% is reabsorbed from the thick ascending limb.
  – Recall that potassium reabsorption in these segments is linked with sodium reabsorption, and is, therefore, relatively constant.
• Variable amount of potassium is reabsorbed from the distal tubule to conserve it when dietary intake is low; when dietary intake is high, potassium is secreted into the nephron.

Alpha-intercalated cells

• In the distal nephron, conserve potassium when dietary intake is low.
• Reabsorb potassium down the electrochemical gradient created by hydrogen-potassium ATPase (aka, pumps).
• The hydrogen-potassium ATPase on the luminal membrane moves hydrogen to the tubule lumen while sending potassium into the tubule cell.
• Potassium then diffuses through the basolateral membrane into the interstitium and capillaries.

Principal cells

• Return excess potassium to the tubular lumen when dietary intake is high.
• Secrete potassium down the electrochemical gradient created by sodium-potassium ATPase.
• Sodium-potassium ATPase moves potassium from the blood into the cell, while projecting sodium from it.
• Potassium then diffuses out of the cell, into the lumen to be excreted in the urine.