Topic 46 - Osmoregulation in the kidney, the countercurrent system

Question 1

Words to include

Answer 1

Osmoregulation

• ​Osmotic homeostasis
• Osmotic environment
• Osmotic balance
• Salt deficiency
• Salt excess
• Shortage of water
• Excess of water
• Isosmotic conditions
  
  • Isovolaemia (shift)
• Hyperosmosis
  
  • Hyperosmotic isovolemia (EC and IC getting balance)
  • Hypothalamic osmoreceptor activity ↑
  • Blood ADH level ↑
  • AQP-2 expression ↑ (distal tubule)
  • Free water celarance ↓
    
    • Water retention
  • Isosmotic
  • Hypervolemia
  • Cause:
    
    • Ø reabsorbed after filtration
      
      • Mannit
      • Glucose
    • Reabsorbed after filtration
      
      • Sodium
  • Aldosterone
    
    • Na⁺ emptying
    • Retention
    • Keeping Na⁺ concentration of the plasma (EC space)
• Hyposomosis
  
  • ADH inhibition → no H₂O retention → hypovolemic isosmosis
  • Osmotic concentration of EC ↓
    
    • Cause:
      
      • Reduced salt intake
      • Primary salt loss
    • Primary hyposmosi
      
      • ADH production and release inhibited
    • Hypovolemic isosmosis
      
      • Free water ↑
      • Clearance ↑

ADH mechanism

• Maintaining isosmosis
• Hypothalamic ADH secreting locus
  
  • Hyposmotic urine (result)
• Diuresis ↑ → extra H₂O load
  
  • Blocked by ADH
• Hydropenia
  
  • Blood-ADH ↑ (result)
• ADH mechanism of action
  
  • Level of action
    
    • Connecting part of distal tubule
    • Collecting duct
  • Reset H₂O permability (result)

Hypovolemia

• Consequence of salt stock ↓
• Hypovolemia
• Activation of Renin Angiotensin System (RAS)
• Angiotensin-II production ↑
  
  • Vasoconstriction
  • Aldosterone stimulation
  • Dypsogenic effect
• Aldosterone production ↑
  
  • Adrenal cortex (location)
• Na⁺ reabsorption ↑
  
  • Distal tubule (location)
• Consequential isosmotic amount of water retention
• Isovolemia

Hypervolemia

• Inhibits RAS
• Mobilizes ANP

Factors influencing volume regulation

• ADH + aldosterone mechanism
  
  • RAS activated
• ANP (Atrial Natiuretic Peptide)
  
  • Ø tubulary Na⁺-reabsorption
    
    • Na⁺-excretion ↑
  • Cardiac atrium (location)
• Volume receptors
  
  • Stretch-recepetors
    
    • Circulation (location)
  • Center of volume regulation
    
    • Diencephalon (around)
• Pressure diuresis
  
  • Elimination of extra volume

Factors creating osmotic gradient

• Na⁺ reabsorption
  
  • Thick ascending limb
  • Na⁺/K⁺/2Cl^- pump
  • Na⁺ pump
    
    • Osmolality of interstitium ↑
• Urea
  
  • Stabilizes hyperosmosis of medulla
  • Interstitial hyperosmosis creates osmotic pressure
• Countercurrent exchanger
• Countercurrent multiper
  
  • _​_Descending limb
    
    • Salt ↑
    • Osmotic concentration ↑
    • Tubular fluid
    • Filtration pressure
  • Osmolaruty
    
    • 300-1200 mosmol/l
    • Cortex → papilla
• Vasa recta​
  
  • Parallel to loop of Henle
  • Osmotically concentrated medullaty areas
    
    • Hyperosmosis of medulla
  • Role:
    
    • Slow blood flow
    • Diffusion equlibrium between interstitium and blood
    • ± iso-osmotic blood leaves the interstitium
    • Ø autoregulation of medullary vessels
    • Maintains medullary hyperosmosis

The coutercurrent systme

• Urine volume and urine osmolality change in a wide range
  
  • Maintainance of isosmosis and isovolemia
• Osmotic layering
  
  • Change quantity and osmolarity of urine
  • Maintinance of osmotic layering
    
    • Countercurrent multiper
    • Countercurrent exchanger
• Osmotic gradient of kidney
  
  • 300-1200 mosmol/l
    
    • From cortex → papilla
  • Hyperosmotic circumstances
    
    • Cells lying deep in medullary portion
    • Omolith formation
• Effect of osmotic gradient:
  
  • Lumen osmolality affected
    
    • Quantity and composition of urine
  • Filtration pressure
  • Possible changes:
    
    • Salts leaves tubule → tubular liquid gets diluted
    • Water leaves tubule → tubular liquid gets concentrated
    • Salt gets in tubule → tubular liquid gets diluted
    • Combination of above

The clearance of free water

• Total amount of osmotically active particles excreted
  
  • Concentration of urine
  • Dilution of urine
  • Osmotic clearance
    
    • amount of plasma cleared of all osmotically active particles per unit time
  • Virtual number
    
    • Diluting kidney
      
      • Free water which the kidney adds to the isosmotic urine(not bound osmotically)
      • Concentrating kidney
        
        • Osmotically free water taken away from the isosmotic urine
• Uosn/Posm = osmotic plateau
  
  • Maximal urine osmolarity
  • Maximal water conservation
  • Omotic plateu, domestic mammals: 4
  • Osmotic plateu, desert animals: 31
• Free water clearande
  
  • C_H2O = V - Cosm

Question 2

Topics to include in the essay

Answer 2

1. Osmoregulation
   
   • Hyperosmosis
   • Hypeosmosis
2. Hypovolemia
3. Hypervolemia
4. ADH-mechanism
   
   • The role of ADH maintaining isosmosis
   • ADH mechanism of action
5. The countercurrent system
6. The osmotic gradient of the kidney
7. Factors creating osmotic gradient
8. The effect of osmotic gradient
9. Clearance of free water

Question 3

Osmoregulation

Role of osmoregulation

Answer 3

• The primary aim is to maintain osmotic homeostasis
  
  • ​A shift in the osmotic environment may destroy physological processes
• If salt deficiency, salt excess, shortage of water or excesso of water occurs, at first the shifted osmotic balance is restored to normal
  
  • Feedback within a couple of minutes
• The fast restoration of isosmosic conditions is usually carried out on the expense of a shift of the isolvolaemia
  
  • ​The organism can for a longer time cope with the volume changes
• Conditions:
  
  • Hyperosmosis
  • Hyposmosis

Question 4

Osmo- and volume regulation

Hyperosmosis

Answer 4

• Hyperosmosis can be created by:
  
  • Substances not able to be reabsorbed after filtration
    
    • ​Eg. mannit and glucose
  • Substances which can be reabsorbed after filtration
    
    • ​Eg. Na⁺
• Aldosterone is in charge of Na⁺ emptying and retention, for keeping the Na⁺ concentration of the plasma at a constant level

1. Hyperosmosis
2. EC and IC getting balance (minutes): hyperosmotic isovolemia
3. Hypothalamic osmoreceptor activity ↑
4. Blood ADH level ↑
5. Distal tubule: AQP-2 expression ↑
6. Free water clearance ↓, water retention
7. Isosmotic → hypervolemia

Question 5

Osmo- and volume regulation

Hyposmosis

Answer 5

ADH inhibition → no H₂O retention → hypovolemic isosmosis​

Question 6

Osmo- and volume regulation

Hypovolemia

Answer 6

• Hypovolemia is stimulated by Renin Angiotensin Syste (RAS) which restores isovolemia
• Reason for hypovolemia:
  
  • ​Salt stock ↓

1. Hypovolemia
2. Activation of Renin Angiotensin System (RAS)
3. Angioten-II production ↑:
   
   1. ​Vasoconstriction
   2. Aldosterone stimulation
   3. dysogenic effect
4. Adrenal cortex: Aldosterone production ↑
5. Na⁺ reabsorption ↑ in distal tubule
6. Consequential isosmotic amount of water retention
7. Isovolemia

Question 7

​Osmo- and volume regulation

Hypervolemia

Answer 7

• Hypervolemia:
  
  • ​Inhibits the functioning of RAS
  • Mobilization ANP

Question 8

ADH-mechanism

The role of ADH in maintaining isosmosis

Answer 8

• Expreimentally perfused kidney produces hyposmotic urine
  
  • ​Reason: Ø endocrine mechanisms → ADH readjusts isosmosis
• Damagage to hypothalamic ADH secreting locus results in hyposmotic urine
• Increased diuresis following extra H₂O load can be promptly blocked by ADH
• Hydropenia results in immediate blood-ADH ↑

Question 9

ADH-mechanism

ADH mechanism of action:

1. Level of action
2. Result

Answer 9

1. Level of action:
   
   • Connecting part of distal tubule
   • Collecting duct
2. Result: resets H₂O permeability

Question 10

Factors influencing volume regulation

Answer 10

1. ADH + aldosterone mechanism
   
   • RAS activated
2. ANP (atrial natriuretic peptide)
   
   • Secretion happens in cardiac atrium
   • Function: Na-excretion ↑, by inhibiting tubulary Na reabsorption
3. Volume receptors
   
   • Stretch-receptors of circulatory system
   • Center of volume regulation : around the diencephalon
4. Pressure diuresis
   
   • Elimination of extra volume

Question 11

Factors creating the osmotic gradient

Give the factors creating the osmotic gradient

Answer 11

1. Na⁺ reabsorption
2. Urea
3. Countercurrent exchanger
4. Countercurrent multiper
5. Vasa recta

Question 12

Factors creating the osmotic gradient

Na⁺ reabsorption

Answer 12

1. ​Active Na⁺ reabsorption of the thick ascending limb
   
   • ​Na⁺/K⁺/Cl^- pump
2. Na⁺-pump increases the osmolality of interstitium
3. Rising osmolality of interstitium attracts water from descending limb permable to water

Question 13

Factors creating the osmotic gradient

Urea

Answer 13

• Circulation of urea stabilizes the hyperosmosis of the medulla
• Result: interstitial hyperosmosis creates suction force (osmotic pressure)

Question 14

Factors creating the osmotic gradient

Countercurrent exchanger

Answer 14

Maintainance of osmotic layering

Question 15

Factors creating the osmotic gradient

Countercurrent multiper

Answer 15

• The increased salt and osmotic concentration of the medullary ISF causes salt to move into the descending limb and water to move out
  
  • Both increase the osmotic concentration of tubular fluid
• Fluid in the lumen continuously moves because of the filtration pressure
• The osmolarity of the kidney tissue increases from 300-1200 mosmol/l from the cortex → papilla

Question 16

Factors creating the osmotic gradient

Vasa recta

Answer 16

• Runs parallel to the Henle loop
• Supplies the osmotically concentrated medullary areas with blood;
• Can keep the hyperosmosis of the medulla because of its anatomical position
• Role of vasa recta:
  
  • 1-2% of renal blood flow flows through
  • Slow blood flow
  • Fluid and solutes can exchange readily between the 2 arms
  • Creates diffusion equilibrium between interstitium and blood
  • ± iso-osmotic blood leaves the interstitium
  • Ø autoregulation of medullary vessels
  • Result: Maintains medullary hyperosmosis
• Ø vasa recta = the high concentration of solutes in the medullary interstitium would be washed out

Question 17

The countercurrent system

Answer 17

• Maintainance of isosmosis and isovolemia requires that urine volume and urine osmolality change in a wide range
  
  • Due to continous water loss via physological processes
• Osmotic layering:
  
  • ​Helps the kidney to change the quantity and osmolarity of the urine with a relatively small energy input very rapidly and with high capacity
  • Osmotic layering is present due to:
    
    • Countercurrent multiplier
    • Countercurrent exchanger

Osmotic gradient of the kideny

• The osmolarity of the kideny increases from 300-1200 mosmol/l from the cortex → papilla
• Cells lying deeper in the medullary portion work unde hyperosmotic conditions
• Camel: Have deep-reaching Henle loops → concentrating ability ↑
• Effect of osmotic gradient:
  
  • ​The osmotic gradient of the interstitium , according to permabiltiy conditions, affects the lumen osmolality and thus the quantitiy and composition of urine
  • Possible changes:
    
    • Salt leaves the tubule: tubular liquid gets diluted
    • Water leaves the tubule: tubular liquid gets concentrated
    • Satl gets in the tubule: tubilar liquid gets concentrated
    • Water gets in the tubule: tubular liquid gets diluted
    • Combination of the above

Question 18

The clearance of free water

Answer 18

• The concentration and dilution of urine can be characterized by the total amount of osmotically active particles excreted:
  
  • Osmotic clearance: the amount of plasma cleared of all osmotically active particles per unit time
  • Virtual number
• Osmotic clearance:
  
  • C_osm = U_osm x V/P_osm
• Free water clearance:
  
  • C_H2O - C_osm
• Osmotic plateau:
  
  • U_osm/P_os
  • Osmotic plateau in domestic mammals = 4
  • Osmotic plateau in desert animals = 31