Topic 45 - Transport at the distal connective tubule and at the collecting tubule

Question 1

Words to include

Answer 1

• Formation of hormonally regulated final urine
  
  • Aldosterone (Na⁺, K⁺)
  • ADH (H₂O)
  • ANP (H₂O)
  • Parathormone (Ca²⁺)
  • Acid-base balance (alkalosis, acidosis
• Cortical collecting tubule (CCT) & conecting tubule (CNT)
  
  • Mineralocorticoid dependent Na⁺ reabsorption
  • Acid-base balance
• Cortical collecting tubule (CCT)
  
  • ADH-dependent water reabsorption
• Medullary collecting tubule (MCT)
  
  • ADH-dependent water reabsorption
  • ADH-dependent urea reabsorption
  • ANP-dependent Na⁺ excretion
• Principal cells
  
  • Acid-base balande
  • K⁺ balance
    
    • K⁺ secretion depends of principal cells
  • Aldosterone dependent apperance
  • Na⁺ canal inhibited by amiloride
• Intercalary cells
  
  • Acid-base balande
  • K⁺ balance
    
    • K⁺ secretion depends of principal cells
  • Intercalar cells type A
    
    • Defense against acidosis
  • Intercalar cells type B
    
    • Defense against alkalosis

Mineralcorticoid dependent Na⁺/K⁺ transport

• Basolateral Na⁺/K⁺ pump
• Luminal Na⁺/K⁺ channels
  
  • Aldosterone dependent apperance
• Na⁺ channel
  
  • Imiloride (inhibits)
• K⁺ transport
  
  • Passive both directions
    
    • Luminal: secretion
    • Basolateral: reabsorption
  • Aldosterone concentration dependent
  • Excess K⁺
    
    • Z. glomerulos
      
      • Aldosterone production
      • Luminal Na⁺ & K⁺ channels expressed

Active water transport

• Osmotic forces
• Paracellularly
• Hormonally regulated water transport
  
  • Aquaphorin-2
    
    • Water channel protein
    • Principal cells
    • ADH effect
      
      • AQP-2 gets to luminal surface
        
        • Facilitates water reabsorption
  • Location:
    
    • Connecting tubule (CNT)
    • Cortical collecting tubule (CCT)
    • Medullary collecting tubule (MCT)

Acid-base balance

• Regulating acid-base balance
  
  • Cortical collecting tubule (CCT)
  • Medullary collecting tubule (MCT)
• Intercalar cells
  
  • Alkalosis
    
    • K⁺ secretion
      
      • Hydrogen pump
    • Hydrocarbonate resorption
    • Hydrocarbonate production & secretion
• Defense against acidosis
  
  • Intercalar cells type A
  • Electrogenic luminal H⁺ pump (ATPase)
  • Carbonic anhydrase
    
    • CO₂
    • OH group
  • HCO₃^-
  • Cl^-/HCO₃^- antiporter
  • Cl^-
    
    • Passive channel
• Defense against alkalosis
  
  • _​_Intercalar cells type B
  • H⁺/K⁺ ATPase pump
  • H⁺ ion: basolateral side → interstitium
  • HCO₃^-/Cl^- antiporter
    
    • Luminal side
    • HCO₃^-: cell → lumen

K⁺ transport

• ↑ plasma K⁺ level → aldosterone secretion
  
  • K⁺ secretion into distal tubule & urine
• Cortical collecting tubule (CCT)
  
  • Principal cells
    
    • Na⁺ reabsorption
    • K⁺ secretion
      
      • Mineralocorticoid dependent
  • Interclary cells
    
    • Reabsorption with H⁺/K⁺ exchange

Question 2

1. Where are the distal connective tubule and the collecting tubule found?
2. Where are the collecting duct found?

Answer 2

1. Distal tubule:
   
   • ​Distal convoluted tubule (DCT)
   • Distal connective tubule (CNT)
2. Collecting duct:
   
   • ​Cortical collecting duct (CCD)
   • Medullary collecting duct (MCD)

Question 3

Transport processes at the connective tubule and collecting tubule

Answer 3

• This is where the formation of the hormonally regulated final urine takes place
  
  • Aldosterone (Na⁺, K⁺)
  • ADH (H₂O)
  • ANP (H₂O)
  • Parathormone (Ca²⁺)
  • Acid-base balance (alkalosis, acidosis)
• Connecting tubule (CNT) & cortical collecting tubule (CCT)
  
  • Mineralocorticoid dependent Na⁺ reabsorption
  • Regulate acid-base balance
• Cortical collecting tubule (CCT)
  
  • ADH-dependent water reabsorption
• Medullary collecting tubule (MCT)
  
  • ADH-dependent water and urea reabsorption
  • ANP-dependent Na⁺ excretion
• Principal cells
  
  • ​Regulation of acid-base and K⁺ balance
  • Levels of K⁺ secretion depends on principal cells
  • Appearance of these proteins are aldosterone dependent
  • Na⁺ canal can be inhibited by amiloride
• Intercalary cells​
  
  • Regulation of acid-base and K⁺ balance
  • Intercalar cells type A
    
    • Defense against acidosis
  • Intercalar cells type B
    
    • Defense against alkalosis

Question 4

Give the different types of transport in the distal connective tubule and the collecting tubule

Answer 4

1. Mineralcorticoid dependent Na⁺/K⁺ transport
2. Active water transport
3. Acid-base balance
4. K⁺ transport

Question 5

Mineralcorticoid dependent Na⁺/K⁺ transport

Answer 5

• Basolateral Na⁺/K⁺ pump
• Luminal Na⁺/K⁺ channels
• The appearance of these proteins is primarily aldosterone dependent
• Na⁺ channel can be inhibited by amiloride
• The transport of K⁺ is passive in both direction, determined by the concentration of aldosterone in the blood:
  
  • Luminal: secretion
  • Basolateral: reabsorption
• If K⁺ is excess z. glomerulosa produce more aldosterone → more luminal Na⁺ and K⁺ channels are expressed

Question 6

Acid-base balance

Answer 6

• The CNT and CCT are the most important tubule sections in the maitainance of the regulated acid-base balance
• In the intercalar cells
  
  • ​K⁺ secretion (hydrogen pump) and hydrocarbonate reabsorption
  • Alkalosis: independent hydrocarbonate production and secretion

Defense against acidosis:​

• Intercalar cells type A
• H⁺ of the water of the cell is forwarded to the lumen by electrogenic luminal H⁺ pump (ATPase)
• The carbonic anhydrase unites the CO₂ entering from the blood side with the OH group
• The formed new HCO₃^- is carried out to the blood by the Cl^-/HCO₃^-antiporter
  
  • The Cl^- leaves through a passive channel

Defense against alkalosis:

• Intercalar cells type B
• H⁺ ion originating from the dissociation of water on the basolateral side is removed by the H⁺/K⁺ ATPase pump to the interstitium
• The HCO₃^-/Cl^- antiporter located on the luminal side removes HCO₃^- from the cell → lumen
• Facilitated by IC carbonic anhydrase which unites CO₂ and OH- groups into HCO₃^-
• The excess K⁺ accumulated in the cell through a passive K+ channel gets back to the interstitium

Question 7

Active water transport

Answer 7

• The flow of water between the renal tubules and the interstitium is directed by the osmotic forces affecting water
• Water moves paracellularly
• In cortical collecting tubule (CCT) and conecting tubulue (CNT) or medullaru collecting tubule (MCT) sections:
  
  • The water transport is a hormonally regulated process which is linked to the special water channel protein of the principal cells (aquaporin-2)
• As an effect of ADH from the surface of the microsomes, the AQP-2 gets to the luminal surface, and facilitates the reabsorption of water

Figure: ADH mediated water transport (distal connected tubule & and collecting duct)

Question 8

K⁺ transport

Answer 8

• 0,1% increase of the plasma K⁺ level provokes aldosterone secretion, which stimulates the K⁺ secretion into the distal tubule (and finally to the urine)
• In CNT, CCT:
  
  • CCT principal cells: Reabsorption of Na⁺ and mineralcorticoid dependent secretion of K⁺
  • CCT intercalary cells: reabsorption with H⁺/K⁺ exchangel