Topic 48 - The maintenance of isovolemia; the renin angiotensin system (RAS), ANP and aldosterone

Question 1

Words to include in the maintainance of isovolemia

Answer 1

• Constant volume

Volume regulation

• ​NaCl uptake and excretion is in balance
• Hyperosmosis
  
  • Extra salt intake
  • Verney-mechanism
• Isosmosis
  
  • Extra salt and water in EC space
  • Hypervolemia
• Effects of extra volume of water on circulation
  
  • Blood voume ↑
  • Arterial pressure ↑
  • Baroreceptors stimulated
  • Periheric vasodilation
  • Oncotic pressure ↓
  • Hemodilution
  • Fluid leaves circulation → interstitium

Question 2

Words to include in the renin angiotensin system (RAS)

Answer 2

• Hypovolemia (regulatory mechanism against)
• Granular cells
• Renin secretion
  
  • Hypovolemia lower Na⁺ load
  • Blood pressure ↓
• Angiotensinogen
  
  • Alpha-2-globulin
  • Liver
• Angiotensin convertase enzyme (ACE)
  
  • Angiotensin-I → angiotensin-II
• Effects opf RAS:
  
  • Renin:
    
    • No direct effect
  • Angiotensin-I
    
    • No direct effect, precursor
  • Angiotensin-II
    
    • Active form
    • Pressor effect
      
      • Peripheral resistance ↑
    • Direct salt retention
      
      • Renal venal constriction
      • RBF/GFR ↓
    • Indirect salt retention
      
      • Stimulator of aldosterone secretion → salt retention
    • Effect on nervous system
      
      • Arterial pressure ↑ by stimulating 4^th ventricle
      • Dypsogenic
      • Peripheral catecholamine synthesis ↑
      • RBF/GFR ↓
      • ADH stimulation
  • Angiotensin-III
    
    • Pressor effect
    • Stimulator of aldosterone secretion

Question 3

Words to include in ANP

Answer 3

• Artial natriuretic peptide (ANP)
• Muscle elements of atria
• Atria stretched → blood stream
• Antihypervolemic effect
  
  • Salt excretion ↑
  • Water retention ↓
• Effects:
  
  • Tubular cells of collecting duct
    
    • cGMP formation
    • cGMP↑= GFR ↑
• Brain Natriueric Peptide (BNP)
  
  • Secreted in ventricles

Question 4

Words to include in aldosterone

Answer 4

Synthesis

• Mineralocorticoid
• Steroid hormone
• Adrenal cortex
  
  • Zona glomerulosa

Role

• Regulator of K⁺ excretion
• Na⁺ reabsorption
  
  • Angiotensin-II induced
• Volume and osmoregulation
  
  • Regulates Na⁺ content of body (EC volume)
    
    • RAS member
• CNS
  
  • Salt hunger ↑

Stimulating factors

• Primary stimulus
  
  • Hyperkalemia
    
    • K⁺ content in plasma
• EC volume or blood pressure ↓→ aldosterone production
• Hypophysis ACTH

Site of action

• Distal tubule
• Connecting duct - cortical section
• Collecting duct - cortical section
• Bind to IC receptor → nucleus
  
  • Na⁺/K⁺ ATPase pump
  • Na⁺ & K⁺​ channel proteins
  • Amiloride
    
    • Inhibits Na⁺ channel
    • Luminal side
• Same effect on:
  
  • ​Salivary gland
  • Sweat gland
  • Epithelial cells of large intestines

Question 5

Topics to include in the essay

Answer 5

1. The maintainance of isovolemia
   
   1. Volume regulation
   2. Effects of extra volume of water on circulation
2. Renin angiotensin system (RAS)
   
   1. Role
   2. Effects of RAS
      
      1. Renin
      2. Angiotensin-I
      3. Angiotensin-II
      4. Angiotensin-III
3. ANP
   
   1. Definition
   2. Site of production
   3. Function
   4. Effects
4. Aldosterone
   
   1. Synthesis
   2. Role
   3. Stimulating factors
   4. Site of action

Question 6

The maintainance of isovolemia

Answer 6

• Isovolemia = constant volume

Volume regulation

• Physological status: NaCl uptak and excretion is balanced
• Extra salt load: elimination takes 1-2 days
• Mechanism: Extra salt intake → hyperosmosis
  
  • ​Turns on the Verney mechanism
• Isosmis is reset within 1-2 hours, but extra salt and water stay in the EC space
  
  • EC spce is extended → hypervolemia

Effect of the extra volume of water on circulation

• Effects:
  
  • Blood volume ↑
  • Arterial pressure ↑
  • Baroreceptors are stimulated
• Result:
  
  • Peripheral vasodilation and oncotic pressure ↓,due to thehemodilution, and therefore fluid leaves thecirculation→interstitium

Question 7

Renin angiotensin system (RAS)

Answer 7

• Regulatory mechanism against hypovolemia
• In the granular cells of JGA the hypovolemia lower Na⁺ load and the fall of the blood pressure elicit renin secretion
• Angiotensinogen:
  
  • ​Belongs to alpha-2-globulin
  • Produced by the liver
• Angiotensin convertase enzyme (ACE) transform angiotensin-I → angiotensin-II

Effects of RAS

• Renin:
  
  • ​No direct effect
• Angiotensin-I:
  
  • No direct effect, precursor
• Angiotensin-II:
  
  • ​Active form
  • Pressor effect: ​peripheral resistance ↑
  • Direct salt retention: stimulator of aldosterone secretion
    
    • ​Result: salt retention
  • Effect on nervous system:
    
    • Increased arterial pressure by stimulating 4^th ventricle
    • Dpsogenic
    • Peripheral catecholamine synthesis ↑
    • RBF/GFR ↓
    • ADH stimulation
• Angiotensin-III
  
  • ​Pressor effect 50% lower than angiotensin-II
  • Stimulation of aldosterone secretion is equivalent with angiotensin-II

Question 8

ANP

Answer 8

• ANP = Atrial Natriuretic Peptide
• Production;
  
  • Produced and stored in the muscle elements of the atria
  • Released into the blood when the atria is stretched
• Function:
  
  • Antihypervolemic effect
    
    • Salt excretion ↑
    • Water retention ↓
• Effects:
  
  • Stimulates the cGMP formation in the tubular cells of the collecting duct
    
    • ​↑ cGMP inhibits the Na⁺ retention​
  • ↑ tubular amount of Na⁺ (GFR↑)
    
    • ​Dialates vas afferent and efferent
    • ↑ RPF → ↑ GFR
• BNP = Brain Natriuretic Peptide
  
  • ​Secreted by cardiac muscle cells in the heart ventricle
  • Similar to ANP in effect

Question 9

Aldosterone

1. Synthesis
2. Role
3. Stimulating factors
4. Site of action

Answer 9

Synthesis

• Mineralocorticoids
• Steroid hormone
• Produced in the zona glomerulosa of the adrenal cortex

Role

• Regulator of the K⁺ excretion
• One of the factors of Na⁺ reabsorption induced by angiotensin-II
• Activation of RAS by either:
  
  1. Dimishing Na⁺ reserves
  2. Reduction in the EC volume
  3. Fall of blood pressure
  • Activation of RAS → Angiotensine-II stimulates the aldosterone production
• Compared to ADH in the volume and osmoregulation:
  
  • ADH: setting the plasma osmolality
  • Aldosterone: regulates the Na⁺ content of the body (EC volume)
    
    • As a member of RAS
• CNS: salt hunger ↑

Stimulating factors

1. Primary stimulus of aldosterone secretion:
   
   • ​​Hyperkalemia (K⁺ concentration in plasma)
2. Aldosterone production is increased when either:
   
   1. EC volume↓
   2. Blood pressure ↓
3. Hypophysis ACTH

Site of action

• Mine site of aldosterone:
  
  • Distal tubule
  • Connecting duct - cortical section
  • Collecting duct - cortical section
• Aldosterone binds to an IC receptor and enters the nucleus
  
  • ​Here it elicits the expression of the:
    
    • Na⁺/K⁺ ATPase pump
    • Na⁺ channel proteins
      
      • ​Amiloride inhibits the Na⁺ channel on the luminal side
    • K⁺ channel proteins
• Aldosterone has the same effect in the:
  
  • Salivary gland
  • Sweat gland
  • Epithelial cells of the large intestines