Topic 47 - The maintenance of Isosmosis; ADH- mechanism

Question 1

Words to include

Answer 1

• Blood volume ↓
• Fluid intake ↓
• Dehydration
• Concentration of dissolved salts ↑
• Osmotic pressure ↑
• Receptors in hypothalamus (reacts to the shift in osmotic pressure)
  
  • Posterior lobe of pituitary
    
    • ADH release
• Hypothalamic thirst center (responds to ADH release)
  
  • ​Water intake
• EC hyperosmosis

The role of ADH maintaining isosmosis

• Vasopressin = antidiuretic hormone (ADH)
• Ensures:
  
  • ​Isosmosis & water conservation
    
    • V2 receptor effect
      
      • cAMP mediated
  • Smooth muscle contraction
    
    • V1 receptor
      
      • IP3 mediated
• Hyposomitc urine
  
  • Ø endocrine mechanisms
    
    • ADH readjust isosmosis
• Damage to hypothalamic ADH secreting locus
  
  • Hyposmotic urine
• Diuresis ↑ → extra H₂O load
  
  • Blocked by ADH
• Hydropenia
  
  • Blood-ADH increase

ADH mediated H₂O transport

• Hypothalamus
  
  • Nucl. supraopticus
  • Nucl. paraventricularis
• Neurohypophysis
• Osmotic concentration of blood ↑
  
  • Water retention
• Collecting ducts
  
  • V2 receptor
  • AQP-2 water channels
• Luminal side
  
  • Transparent to water
    
    • Reabsorbed according to osmotic gradient
• Blood pressure ↑
  
  • Ø ADH production
    
    • Baroreceptors
• Aquaporine-1
• Aquaporine-2

ADH mechanism of action

• Level of action:
  
  • Connecting part of distal tubule
  • Collecting duct
• H₂O permabilty

Hyperosmosis

• Substances not reabsorbed after filtration
  
  • Mannit
  • Glucose
  • Substances reabsorbed after filtration
    
    • Sodium

1. Hyperosmosis
2. Hyperosmotic isovolemia (EC and IC balance)
3. Hypothalamic osmoreceptor activity ↑
4. Blood ADH level ↑
5. AQP-2 expression ↑ (distal tubule)
6. Free water clearance, water retention
7. Isosmotic hypervolemia

Hyposmosis

• ADH inhibition → no H₂O retention → hypovolemic isoosmosis

Figure

• ADH secretion from neurohypophysis
• Hyperosmosis of plasma (EC) +
  
  • Primary factor
• Osmoreceptors (hypothalamus) +
• Stress +
• Pain +
• Baroreceptors (arcus aortae, sinus aorticus) ÷
  
  • Blood pressure ↑
• Stress, volume receptors (left atrium, lungs) ÷
• ANP production (central and atrial) ÷
• External effects
  
  • AQP-2 expression
  • Water retention
• Bleeding
  
  • V1 receptor stimulation
    
    • Vessel contraction
• ACTH-like
  
  • Corticoid production ↑
• Renal effects +
  
  • AQP-2 expression
    
    • Water retention
• DCT and collecting duct
  
  • AQP-2 expression
    
    • Water retention

Question 2

The maintainance of isosmosis

Answer 2

• When blood volume is reduced as a result of decreased fluid intake or injury, the body gets dehydrated
• Concentration of salts dissolved in the blood increases
  
  • Causing a rise in osmotic pressure
• Receptors in the hypothalamus react to the shift in osmotic pressure
  
  • ​Trigger posterior lobe of the pituitary to activate release of ADH
• At the same time, the thirst center in hypothalamus responds by stimulating the sensation of thirst → water intake
• Adequate stimulus is the EC hyperosmosis

Hyperosmosis

• Can be created by:
  
  • Substances which can not be reabsorbed after filtration
    
    • ​Eg. Mannit and glucose
  • Substances which can be reabsorbed after filtration
    
    • ​Eg. Na⁺

1. Hyperosmosis
2. EC and IC getting balance: 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

Hyposmosis

• ADH inhibition → no H₂O retention → isosmotic hypovolemia
• In case of reduced salt intake or primary salt loss the osmotic concentration of EC ↓

Question 3

ADH

Define ADH

Answer 3

• Vasopressin = antidiuretic hormone (ADH)
• It is a hormone made by the hypothalamus and stored in the posterior pituitary gland
• Role:
  
  • It tells the kidneys how much water to conserve
  • Regulates and balances the amount of water in blood

Question 4

ADH

The role of ADH maintaining isosmosis

Answer 4

ADH effects on the kidney:

• Ensures isosmosis and water conservation
  
  • Effect via V2 receptor (cAMP mediated)
• Smooth muscle contraction effect
  
  • Effect via V1 receptor (IP3 mediated)

1. The most important effect of ADH is to conserve body water by reducing the loss of water in urine
   
   • ​A diuretic is an agent that increases urine formation
2. ADH stimulates water reabsorption by stimulating insertion of aquaphorins (water channels) into the membranes of the kidney tubules. These channels transport water through tubular cells and back into blood
   
   • ​Result:
     
     • Plasma osmolarity of urine ↓
     • ​Osmolarity of urine↑

• Experimentally perfused kidney produces hyposmotic urine
  
  • Reason:Ø endocrine mechanisms → ADH readjusts isosmosis
• Damage to hypothalamic ADH secreting locus
  
  • ​Results: Hyposmotic urine
• Increased diuresis → extra H₂O load can be promptly blocked by ADH
• Hydropenia
  
  • ​Result: immediate blood-ADH increase

ADH effect on the vascular system

• High concentration of ADH cause vasoconstriction of arterioles → arterial pressure ↑

Question 5

ADH

Mechanism of action

Answer 5

• Level of action:
  
  • Connecting part of distal tubule
  • Collecting duct
• Result: H₂O permability

Question 6

ADH

ADH mediated H₂O transport

Answer 6

• ADH is produced in the hypothalamus
  
  • ​Nucl. supraoticus
  • Nucl. paraventricularis
• Gets to neurohypophysis
• Released when osmotic concentration of the blood ↑
• Above 300 mosmol/l, plasma osmolarity ADH production ↑
  
  • ​Result: water retention
• V2 receptors of the collecting ducts stimulate the apperance of aquaphorpine-2, water channe proteins
• The luminal side becomes transparent to water
  
  • Water according to the osmotic gradient is reabsorbed
• ADH production is inhibited by increase in blood pressure
  
  • ​Through baroreceptors

Question 7

ADH

• Give example of an pathological condition*
• Ikke nødvendig å kunne*

Answer 7

• Diabetes insipidus, can arise from two situations
  
  • Hypothalamic diabetes: ​Deficiency in secretion of ADH from the posterior pituitary
  • Nephrogenic diabetes: The kidney is unable to respond to ADH
• Symptoms: excessive urine production

Question 8

ADH

Mechanism, figure

Answer 8