Exam 2: Urine Concentration and Dilution I & II

Question 1

žDefine the main organ that regulates water balance and why

Answer 1

• Kindeys
  
  • For the bodies water balance!
    
    • Water Intake = Water Output

Question 2

žDescribe how urine osmolality and urine output can vary

and then calculate how this plays a role with the amount of Osmoles excreted/day

Answer 2

• žUrine Osmolality
  
  • Normal diet
    
    • kidneys excrete ~ 600 mOsmol/day of solute
  • žž*** Osmoles excreted/day = Uosm x V of Urine output/day ***
    
    • 600 mOsmol/day = Uosm x V of Urine output/day
    • If osm inc/dec, then volume has to inc/dec so excreted remains constant!
• Urine Output
  
  • V = Cosm + CH₂O
    
    • CH₂O = free-water clearance (mL/min)
    • V = urine flow rate (mL/min)
    • Cosm = osmolar clearance ((UosmV)/Posm) (mL/min)
  • The wide range of CH₂O represents the kidneys’ attempt to stabilize the osmolality of the ECF in the face of changing loads of solutes and water
    
    • CH₂O can be as high as + 18 L/Day under maximally diluting conditions
    • CH₂O can be as little as - 1.5 L/Day under maximally concentrating conditions

Question 3

žCalculate urine output based on urine clearance and water clearance

Answer 3

• Free Water Clearance (means how much water is being lost)
  
  • Estimate the ability to concentrate or dilute urine
    
    • Negative CH₂0 = kidney removes water; concentrated urine
    • Positive CH₂0 = kidney generates water; dilute urine
• *** CH₂O = V – Cosm ***
  
  • CH2O = free-water clearance (mL/min)
  • V = urine flow rate (mL/min)
  • Cosm = osmolar clearance ((UosmV)/Posm) (mL/min)

Question 4

žCalculate and understand Isosmotic urine

Answer 4

• Isosmotic Urine
  
  • Osmolality of the urine and plasma are the same
    
    • Uosm = Posm
    • CH₂O = 0

Question 5

žCalculate and understand Hyposmotic** urine

Answer 5

• Hyposmotic (Dilute) Urine
  
  • V > Cosm
  • CH₂O is positive; free water movement
  • Uosm < Posm
  • Circulating ADH levels are LOW
    
    • high water intake
    • Central diabetes
      
      • low levels of ADH
    • Nephrogenic diabetes insipidus
      
      • ADH is ineffective

Question 6

žCalculate and understand Hyperosmotic** urine

Answer 6

• Hyperosmotic (Concentrated) urine
  
  • V < Cosm
  • CH₂O is negative
  • Uosm > Posm
  • Circulating ADH levels are high
    
    • Water deprivation
    • Volume depletion
    • SIADH
  • kidney removes water

Question 7

žDifferentiate how the kidney generates dilute urine versus concentrated urine

Answer 7

• žKidneys will dilute or concentrate urine as needed to regulate water balance
  
  • Increase urine volume
    
    • decrease urine osmolality
  • Decrease urine volume
    
    • increase urine osmolality
  • If you don’t see these in opposite then something is going on!
• žRenal failure reduces both the concentrating and diluting ability

Question 8

žDescribe the three components involved urine output

Answer 8

1. Adequate glomerular filtration
   
   • Needed to deliver NaCl and water to the loop of Henle
2. Na+ reabsorption without water reabsorption in the ascending limb of the loop of Henle
   
   • Dilutes tubular fluid
   • Creates the hypertonic medullary interstitial fluid
3. Water permeability in the collecting duct
   
   • Controlled by ADH

Question 9

Water Deprivation overview

Answer 9

• Water Deprivation
  
  • Increases Posm
• Stimulates osmoreceptors in anterior hypothalamus
  
  • Increases secretion of ADH from posterior pituitary
    
    • Increases water permeability of late distal tubule and collecting duct
      
      • Increases water reabsorption
• Increases Uosm and decreases Vurine
  
  • Decreases Posm toward normal

Question 10

How is urine concentrated by location

Answer 10

• Increased levels of ADH
  
  • Proximal tubule: no change in osm
  • Loop of Henle:
    
    • hypotonic to plasma
      
      • by the end of the thick ascending limb (diluting segment)
  • CDT:
    
    • increase in ADH
    • increase in water permeability
      
      • increases osm
  • CCT: No change
  • MCD:
    
    • osm increases because of
      
      • hyperosmolality of the medullary interstitium
      • and ADH that raises the water permeability

Question 11

žDescribe the three components involved in the generation of the hyperosmotic medulla

Answer 11

1. Loop of Henle
   
   • Remove NaCl and deposit in interstitium of renal medulla
   • Salt reabsorption increases the osmolality of the interstitium and decreases osmolality of the fluid within the lumen
   • Because NaCl is pumped out of the rather water-impermpeable loop of Henle, the tubule fluid at the end is hypo-osmotic in both antidiuresis and water diuresis
   • Countercurrent system can enhance the osmotic gradient
   • ADH augments NaCl reabsorption in the thick ascending limb
2. Urea concentration contributes to the high osmolality of the medullary interstitium
   
   • Augmented by ADH
3. Vasa recta
   
   • Maintains the osmotic gradient

Question 12

Antidiuresis

Answer 12

• Excrete 15% of filtered urea
• IMCD reabsorbs 55% of urea into the medullary interstitium
• Vasa Recta and Loop of Henle reabsorb solute from the medullary interstitium

Question 13

žDescribe the clinical outcomes when:

žLow urea levels

Answer 13

• Low urea levels
  
  • Low protein intake
  • Children < 1 yo
• Reduced capacity to concentrate their urine

Question 14

Countercurrent Multiplier of the Loop of Henle

Answer 14

• Countercurrent arrangement of the loop of Henle magnifies the osmotic work that a single ascending limb can perform
• At any level, osmolality in the lumen of the ascending limb is lower than it is in the interstitium
• Depends on NaCl reabsorption in the thick ascending limb and countercurrent flow in the descending and ascending limbs of the loop of Henle
• Augmented by ADH
  
  • Presence of ADH increases the size of the corticopapillary osmotic gradient

Question 15

Vasa Recta

Answer 15

• Countercurrent configuration that traps solutes in the medulla
• Only 5-10% of total renal plasma flow
  
  • Passive exchange of water and solutes
  • Descending vasa recta to gain solute and lose water
  • Ascending to lose solute and gain water
    
    • Descending and ascending vessels exchange solutes and water at the expense of the medullary interstitium
    • Medullary blood flow increases in states of low ADH

Question 16

Water Intake overview

Answer 16

• Water Intake
  
  • Decreases Posm
• Inhibits osmoreceptors in anterior hypothalamus
  
  • Decreases secretion of ADH from posterior pituitary
    
    • Decreases water permeability of late distal tubule and collecting duct
      
      • Decreases water reabsorption
• Decreases Uosm and increases Vurine
  
  • Increases Posm toward normal

Question 17

How is urine diluted by location

water diuresis

Answer 17

• Decreased levels of ADH
  
  • Proximal tubule: no change in osm
  • Loop of Henle:
    
    • hypotonic to plasma
      
      • by the end of the thick ascending limb (diluting segment)
  • CDT:
    
    • decrease in ADH
    • limited water permeability
      
      • pumping salt out of tubule
  • CCT:
    
    • pumping salt out of tubule
  • MCD:
    
    • pumping salt out of tubule

Question 18

žDescribe the clinical outcomes for:

Primary polydipsia

Answer 18

• Excessive fluid intake in the absence of physiological stimuli to drink
• Serum ADH = Decreased
• Serum Osm = Decreased
• Urine Osm = Hyposmotic
• Urine flow rate = High
• CH₂O = Positive

Question 19

žDescribe the clinical outcomes for:

Central diabetes Insipidus

Answer 19

• Failure of ADH secretion
• Serum ADH = Decreased
• Serum Osm = Increased (too much H₂O excretion)
• Urine Osm = Hyposmotic
• Urine flow rate = High
• CH₂O = Positive

Question 20

žDescribe the clinical outcomes for:

Nephrogenic diabetes Insipidus

Answer 20

• Kidneys don’t respond to ADH
• Serum ADH = Increased
• Serum Osm = Increased (too much H₂O excretion)
• Urine Osm = Hyposmotic
• Urine flow rate = High
• CH₂O = Positive

Question 21

žDescribe the clinical outcomes for:

Water deprivation

Answer 21

• No water intake
• Serum ADH = Increased
• Serum Osm = High - normal
• Urine Osm = Hyperosmotic
• Urine flow rate = Low
• CH₂O = Negative

Question 22

žDescribe the clinical outcomes for:

SIADH

(Syndrome of inappropriate antidiuretic hormone secretion)

Answer 22

• Secrete high levels of ADH
  
  • Increases water reabsorption by the collecting ducts
• Serum ADH = Super Increased
• Serum Osm = Decreased- reabsorption of too much H2O
• Urine Osm = Hyperosmotic
• Urine flow rate = Low
• CH₂O = Negative
• Oat Cell carcinomas of the lung may secrete ADH that is unregulated.
  
  • As a result, blood levels of ADH can become extraordinarily high.

Question 23

Diabetes Insipidus:

žCentral DI vs. žNephrogenic DI

Answer 23

• Central DI
  
  • Failure of ADH secretion
  • Administer ADH
  • Rapidly increases urine osmolarity more than 50%
• Nephrogenic DI
  
  • Kidneys respond inadequately to ADH (receptors!)
  • Administer ADH
  • Less of an increase in urine osmolarity compared to central DI