Control of Water Balance - Muster

Question 1

If a patient has a POSITIVE water balance or low plasma osmolality (<285), what would be the resulting compensatory urine osmolality and the urine volume?

Answer 1

• LOW plasma/serum osmolality →
  
  • low urine osmolality
  • increased urine volume

Question 2

If a patient has a NEGATIVE water balance or high plasma osmolality (>300), what would be the resulting compensatory urine osmolality and the urine volume?

Answer 2

• HIGH plasma/serum osmolality →
  
  • high urine osmolality
    
    • heavily concentrated
  • low urine volume
    
    • (want to hang onto water)

Question 3

What/Where are the systemic sensors for maintenance of water balance?

Answer 3

• Osmolality
  
  • Osmoreceptors in Brain
    
    • sense high sodium
• Volume
  
  • Carotid and Atrial Baroreceptors
    
    • sense changes in MAP = CO x SV

Question 4

What is the role of ADH in water homeostasis? Primary mode of action? Location of effect?

Answer 4

• Regulates reabsorption of water
  
  • alters the availability of water channels (AQP2)
  • Insert aquaporins into collecting tubules in distal medullary space

Question 5

What is the role of the Vasa Recta in helping to maintain a high interstitial medullary gradient?

Answer 5

• Track the shape of the Loop of Henle
  
  • hairpin configuration
• Maintain interstitial concentration gradient
  
  • helps get H₂O back into circulation
  • allows production of concentrated urine

Question 6

How does ADH upregulate aquaporins in the collecting tubule?

Answer 6

• Posterior pituitary => makes ADH
  
  • enters systemic circulation
• ADH leaves peritubular capillaries near collecting ducts
• Binds to V₂ receptor
• G-protein couple receptor → causes conformational change
• Upregulation of cAMP
• Activates cAMP
• Activates cAMP Response Element Binding Protein (CREB-P)
  
  • transcription factor
• CREB-P promotes txn & translation of Aquaporins
• Microtubules allow AQP2 to insert into luminal side of collecting duct
  
  • reabsorb water from urine!

Question 7

What drug blocks the V₂ receptor that ADH binds to in the collecting duct and forces H₂O diuresis?

Answer 7

Tolvaptan

(approved for heart failure)

Question 8

What does a genetic mutation of the V₂ receptor in the collecting tubule result in?

Answer 8

Nephrogenic Diabetes Insipidus

• prevent adequate response to ADH
• causes water loss

Question 9

What percentage of water is reabsorbed in each tubular section of the nephron?

Answer 9

• Proximal Tubule = 65%
• Loop of Henle = 10%
• Collecting Duct = 5-24.5%
  
  • largely variable

Question 10

What is the theoretical excretion of filtered water with/without ADH in Liters?

Answer 10

• With ADH
  
  • 0.5% → <1L
• Without ADH
  
  • 20% → 36L

Question 11

What is the physiology in the loop of henle that contributes to water balance?

Answer 11

• Descending limb
  
  • permeable to water
  • luminal osmolality starts at 300 mOsm
• Ascending limb
  
  • NKCC pump
  • UT2 (transport urea down gradient)
• Interstitial osmolality
  
  • variable
    
    • 300-600 without ADH (NaCl)
    • 300-1200 with ADH (NaCl + Urea)

Question 12

What is the physiology in the collecting duct that contributes to water balance?

Answer 12

• Transporters with ADH (reabsorb H₂O)
  
  • UT1 (transport urea down gradient)
  • AQP2 (allow diffusion of water)
• Interstitial osmolality
  
  • variable
    
    • 300-600 without ADH (NaCl)
    • 300-1200 with ADH (NaCl + Urea)
• Luminal osmolality
  
  • Highly variable
    
    • 50-1,000 mOsms