Renal regulation

    Regulation of the
volume and composition
of extracellular fluid (ECF)

                              1
Overview



   Text




           2
Overview
• What is regulated for
  ECF: (outputs)


                          Text




                                 2
Overview
• What is regulated for
  ECF: (outputs)
  – water

                          Text




                          ...
Overview
• What is regulated for
  ECF: (outputs)
  – water
  – Na+
                          Text




                   ...
Overview
• What is regulated for
  ECF: (outputs)
  – water
  – Na+
  – K+                    Text




                   ...
Overview
• What is regulated for
  ECF: (outputs)
  –   water
  –   Na+
  –   K+                     Text

  –   other sol...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Overview
• What is regulated for         • Sensors for ECF
  ECF: (outputs)                  composition: (inputs)
  –   w...
Regulation of glomerular
        filtration




                           3
As BP goes up, glomerular filtration goes
up                                          4
Keep a list of autoregulation


Autoregulation




                                 5
Keep a list of autoregulation


          Autoregulation
Apart from neural regulation, there are
  2 ways that the kidneys...
Keep a list of autoregulation


          Autoregulation
Apart from neural regulation, there are
   2 ways that the kidney...
Keep a list of autoregulation


          Autoregulation
Apart from neural regulation, there are
   2 ways that the kidney...
Myogenic autoregulation




                          6
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.




      ...
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.
• Therefor...
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.
• Therefor...
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.
• Therefor...
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.
• Therefor...
Myogenic autoregulation
• Arteriolar smooth muscle responds to
  stretch like other muscles – by
  contracting.
• Therefor...
Tubuloglomerular Feedback




                            7
Tubuloglomerular Feedback
• This effect depends on special
  structure – the juxtaglomerular
  apparatus.




            ...
Tubuloglomerular Feedback
• This effect depends on special
  structure – the juxtaglomerular
  apparatus.
• macula densa c...
Tubuloglomerular Feedback
• This effect depends on special
  structure – the juxtaglomerular
  apparatus.
• macula densa c...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Thousands of nefrons are all regulated to give regular flow.
Increased flow to the glomerulus leads to increased filtratio...
Sympathetic nerves




                     9
Sympathetic nerves
• The sympathetic division of the ANS
  innervates both:




                                        9
Sympathetic nerves
• The sympathetic division of the ANS
  innervates both:
  – afferent arterioles




                  ...
Sympathetic nerves
• The sympathetic division of the ANS
  innervates both:
  – afferent arterioles
  – efferent arteriole...
Sympathetic nerves
• The sympathetic division of the ANS
  innervates both:
  – afferent arterioles
  – efferent arteriole...
Sympathetic nerves
• The sympathetic division of the ANS
  innervates both:
  – afferent arterioles
  – efferent arteriole...
Sympathetic nerves (2)




                         10
Sympathetic nerves (2)
• Vasoconstriction of the afferent
  arteriole  ↓ blood flow & ↓ GFR




                          ...
Sympathetic nerves (2)
• Vasoconstriction of the afferent
  arteriole  ↓ blood flow & ↓ GFR
• Constricting the efferent ar...
Sympathetic nerves (2)
• Vasoconstriction of the afferent
  arteriole  ↓ blood flow & ↓ GFR
• Constricting the efferent ar...
Sympathetic nerves (2)
• Vasoconstriction of the afferent
  arteriole  ↓ blood flow & ↓ GFR
• Constricting the efferent ar...
Hormonal regulation

  mainly, effects on the
  movement of specific
      substances


                           11
Hormone overview:




                    12
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:




                                 ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II




           ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Hormone overview:
• Any hormone that affects average systemic BP
   effects on GFR:
  
 especially Ang II
• 3 hormones  ...
Remember diuresis to remember antiduresis

      ADH naming




                                            13
Remember diuresis to remember antiduresis

             ADH naming
• ADH = anti-diuretic hormone




                     ...
Remember diuresis to remember antiduresis

             ADH naming
• ADH = anti-diuretic hormone
• diuresis is a condition...
Remember diuresis to remember antiduresis

             ADH naming
• ADH = anti-diuretic hormone
• diuresis is a condition...
Remember diuresis to remember antiduresis

                ADH naming
•   ADH = anti-diuretic hormone
•   diuresis is a co...
Remember diuresis to remember antiduresis

                ADH naming
•   ADH = anti-diuretic hormone
•   diuresis is a co...
ADH mechanism of action




                          14
ADH mechanism of action

  ↑ water permeability of collecting
  tubules




                                         14
ADH mechanism of action

  ↑ water permeability of collecting
  tubules

  ↑ passive diffusion of water
  (“osmosis”) du...
ADH mechanism of action

  ↑ water permeability of collecting
  tubules

  ↑ passive diffusion of water
  (“osmosis”) du...
Regulation of ADH




                    15
Regulation of ADH
• ↑ osmotic pressure  “osmoreceptors”
  of the hypothalamus with no blood-
  brain barrier




        ...
Regulation of ADH
• ↑ osmotic pressure  “osmoreceptors”
  of the hypothalamus with no blood-
  brain barrier
• The osmore...
Regulation of ADH
• ↑ osmotic pressure  “osmoreceptors”
  of the hypothalamus with no blood-
  brain barrier
• The osmore...
Regulation of ADH
• ↑ osmotic pressure  “osmoreceptors”
  of the hypothalamus with no blood-
  brain barrier
• The osmore...
Regulation of ADH
• ↑ osmotic pressure  “osmoreceptors”
  of the hypothalamus with no blood-
  brain barrier
• The osmore...
16
17
Aldosterone




              18
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 




                                            18
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 

 
 
    
   ↑ K+ excretion




                        ...
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 

 
 
    
   ↑ K+ excretion

 
 
    
   ↑ Na+ retention...
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 

 
 
    
    ↑ K+ excretion

 
 
    
    ↑ Na+ retenti...
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 

 
 
    
    ↑ K+ excretion

 
 
    
    ↑ Na+ retenti...
Aldosterone
• Aldosterone acts on cells of the distal
  tubules 

 
 
    
    ↑ K+ excretion

 
 
    
    ↑ Na+ retenti...
Negative FB for   K +




                        19
Renin-angiotensin system




                           20
Renin-angiotensin system
An example of a regulatory cascade:




                                      20
Renin-angiotensin system
An example of a regulatory cascade:

 Liver  Angiotensinogen in blood
  plasma




             ...
Renin-angiotensin system
An example of a regulatory cascade:

 Liver  Angiotensinogen in blood
  plasma

 JG cells of aff...
Renin-angiotensin system
An example of a regulatory cascade:

 Liver  Angiotensinogen in blood
  plasma

 JG cells of aff...
Renin-angiotensin system
An example of a regulatory cascade:

 Liver  Angiotensinogen in blood
  plasma

 JG cells of aff...
Ang II actions




                 21
Ang II actions
• Ang II is a powerful vasoconstrictor




                                         21
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
Ang II actions
• Ang II is a powerful vasoconstrictor
  – Ang II also “resets” the sensitivity of the
    CV regulatory re...
↓   renal BP  ↑ renin




                         22
↓        renal BP  ↑ renin
1.  direct stimulation of JG cells 




                                        22
↓        renal BP  ↑ renin
1.  direct stimulation of JG cells 

 
      
    ↑ renin




                              ...
↓       renal BP  ↑ renin
1.  direct stimulation of JG cells 

 
      
    ↑ renin
2. baroreceptor reflex  ↑ sympathet...
↓       renal BP  ↑ renin
1.  direct stimulation of JG cells 

 
      
    ↑ renin
2. baroreceptor reflex  ↑ sympathet...
↓       renal BP  ↑ renin
1.  direct stimulation of JG cells 

 
      
    ↑ renin
2. baroreceptor reflex  ↑ sympathet...
↓       renal BP  ↑ renin
1.  direct stimulation of JG cells 

 
      
    ↑ renin
2. baroreceptor reflex  ↑ sympathet...
Hormone table
Hormon          Action   Stimulu Type of
e        Source s        s       regulation
Epi


ADH


Aldos


Ang...
Integrated ECF regulation




                            24
Maintaining ECF




                  25
Maintaining ECF
• Maintenance of the ECF operates on:




                                        25
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)




                   ...
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)
  – volume of water in ...
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)
  – volume of water in ...
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)
  – volume of water in ...
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)
  – volume of water in ...
Maintaining ECF
• Maintenance of the ECF operates on:
  – concentrations of electrolytes (& water)
  – volume of water in ...
Regulation involved




                      26
Regulation involved
• Renal regulation involves a number of
  hormonal and paracrine mechanisms,




                     ...
Regulation involved
• Renal regulation involves a number of
  hormonal and paracrine mechanisms,
  – and is therefore some...
Regulation involved
• Renal regulation involves a number of
  hormonal and paracrine mechanisms,
  – and is therefore some...
Regulation involved
• Renal regulation involves a number of
  hormonal and paracrine mechanisms,
  – and is therefore some...
Regulation involved
• Renal regulation involves a number of
  hormonal and paracrine mechanisms,
  – and is therefore some...
27
Shock




        28
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:




                   ...
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:
  – ↓ BP




          ...
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:
  – ↓ BP
  – HR often ↑...
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:
  – ↓ BP
  – HR often ↑...
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:
  – ↓ BP
  – HR often ↑...
Shock
• Clinically, shock describes a
  condition in which the
  cardiovascular system is failing:
  – ↓ BP
  – HR often ↑...
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  • 7 A Renal Reg

    1. 1. Renal regulation Regulation of the volume and composition of extracellular fluid (ECF) 1
    2. 2. Overview Text 2
    3. 3. Overview • What is regulated for ECF: (outputs) Text 2
    4. 4. Overview • What is regulated for ECF: (outputs) – water Text 2
    5. 5. Overview • What is regulated for ECF: (outputs) – water – Na+ Text 2
    6. 6. Overview • What is regulated for ECF: (outputs) – water – Na+ – K+ Text 2
    7. 7. Overview • What is regulated for ECF: (outputs) – water – Na+ – K+ Text – other solutes (glucose, amino acids, etc.) 2
    8. 8. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – Na+ – K+ Text – other solutes (glucose, amino acids, etc.) 2
    9. 9. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – baroreceptors – Na+ – K+ Text – other solutes (glucose, amino acids, etc.) 2
    10. 10. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – baroreceptors – Na+ – volume receptors – K+ Text – other solutes (glucose, amino acids, etc.) 2
    11. 11. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – baroreceptors – Na+ – volume receptors – K+ Text – osmoreceptors – other solutes (glucose, amino acids, etc.) 2
    12. 12. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – baroreceptors – Na+ – volume receptors – K+ Text – osmoreceptors – other solutes (glucose, – K+ amino acids, etc.) 2
    13. 13. Overview • What is regulated for • Sensors for ECF ECF: (outputs) composition: (inputs) – water – baroreceptors – Na+ – volume receptors – K+ Text – osmoreceptors – other solutes (glucose, – K+ amino acids, etc.) – Na+ 2
    14. 14. Regulation of glomerular filtration 3
    15. 15. As BP goes up, glomerular filtration goes up 4
    16. 16. Keep a list of autoregulation Autoregulation 5
    17. 17. Keep a list of autoregulation Autoregulation Apart from neural regulation, there are 2 ways that the kidneys “self- regulate”. 5
    18. 18. Keep a list of autoregulation Autoregulation Apart from neural regulation, there are 2 ways that the kidneys “self- regulate”. 1. myogenic autoregulation – responses to stretch of the arteriolar smooth muscle 5
    19. 19. Keep a list of autoregulation Autoregulation Apart from neural regulation, there are 2 ways that the kidneys “self- regulate”. 1. myogenic autoregulation – responses to stretch of the arteriolar smooth muscle 2. tubuloglomerular autoregulation – responses to flow through the distal tubules 5
    20. 20. Myogenic autoregulation 6
    21. 21. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. 6
    22. 22. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. • Therefore, ↑ BP  ↑ stretch  6
    23. 23. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. • Therefore, ↑ BP  ↑ stretch  ↑ contraction  ↓ filtration pressure 6
    24. 24. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. • Therefore, ↑ BP  ↑ stretch  ↑ contraction  ↓ filtration pressure  ↓ GFR (constant) 6
    25. 25. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. • Therefore, ↑ BP  ↑ stretch  ↑ contraction  ↓ filtration pressure  ↓ GFR (constant) • The reverse, ↓ BP  little myogenic response, because the renal arterioles are normally nearly completely relaxed; 6
    26. 26. Myogenic autoregulation • Arteriolar smooth muscle responds to stretch like other muscles – by contracting. • Therefore, ↑ BP  ↑ stretch  ↑ contraction  ↓ filtration pressure  ↓ GFR (constant) • The reverse, ↓ BP  little myogenic response, because the renal arterioles are normally nearly completely relaxed; net effect is ↓ GFR due to ↓ BP directly. 6
    27. 27. Tubuloglomerular Feedback 7
    28. 28. Tubuloglomerular Feedback • This effect depends on special structure – the juxtaglomerular apparatus. 7
    29. 29. Tubuloglomerular Feedback • This effect depends on special structure – the juxtaglomerular apparatus. • macula densa cells of the distal convoluted tubule (the sensor) 7
    30. 30. Tubuloglomerular Feedback • This effect depends on special structure – the juxtaglomerular apparatus. • macula densa cells of the distal convoluted tubule (the sensor) • neighboring juxtaglomerular cells of the afferent arteriole of the same nephron (the effector) 7
    31. 31. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) 8
    32. 32. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule 8
    33. 33. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule  stimulation of macula densa cells 8
    34. 34. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule  stimulation of macula densa cells  release of paracrine secretions 8
    35. 35. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule  stimulation of macula densa cells  release of paracrine secretions (including NO) 8
    36. 36. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule  stimulation of macula densa cells  release of paracrine secretions (including NO) The neighboring afferent arteriole cells respond with ↑ constriction  ↓ GFR & ↓ flow 8
    37. 37. Thousands of nefrons are all regulated to give regular flow. Increased flow to the glomerulus leads to increased filtration. This leads to more flow of fluid through the nefron. Tubuloglomerular (2) ↑ flow of fluid through the distal tubule  stimulation of macula densa cells  release of paracrine secretions (including NO) The neighboring afferent arteriole cells respond with ↑ constriction  ↓ GFR & ↓ flow This is a simple negative feedback to maintain ~ constant flow through the 8
    38. 38. Sympathetic nerves 9
    39. 39. Sympathetic nerves • The sympathetic division of the ANS innervates both: 9
    40. 40. Sympathetic nerves • The sympathetic division of the ANS innervates both: – afferent arterioles 9
    41. 41. Sympathetic nerves • The sympathetic division of the ANS innervates both: – afferent arterioles – efferent arterioles 9
    42. 42. Sympathetic nerves • The sympathetic division of the ANS innervates both: – afferent arterioles – efferent arterioles • α receptors mediate vasoconstriction in response to sympathetic activity. 9
    43. 43. Sympathetic nerves • The sympathetic division of the ANS innervates both: – afferent arterioles – efferent arterioles • α receptors mediate vasoconstriction in response to sympathetic activity. • The 2 types of arterioles can be separately controlled. 9
    44. 44. Sympathetic nerves (2) 10
    45. 45. Sympathetic nerves (2) • Vasoconstriction of the afferent arteriole  ↓ blood flow & ↓ GFR 10
    46. 46. Sympathetic nerves (2) • Vasoconstriction of the afferent arteriole  ↓ blood flow & ↓ GFR • Constricting the efferent arterioles  ↑ filtration pressure & ↑ GFR 10
    47. 47. Sympathetic nerves (2) • Vasoconstriction of the afferent arteriole  ↓ blood flow & ↓ GFR • Constricting the efferent arterioles  ↑ filtration pressure & ↑ GFR • Most of the important regulation involves the afferent arterioles. 10
    48. 48. Sympathetic nerves (2) • Vasoconstriction of the afferent arteriole  ↓ blood flow & ↓ GFR • Constricting the efferent arterioles  ↑ filtration pressure & ↑ GFR • Most of the important regulation involves the afferent arterioles. • But a large ↓ in systemic BP  strong sympathetic vasoconstriction  ↓ GFR 10
    49. 49. Hormonal regulation mainly, effects on the movement of specific substances 11
    50. 50. Hormone overview: 12
    51. 51. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: 12
    52. 52. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II 12
    53. 53. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: 12
    54. 54. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin) 12
    55. 55. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin)  regulation of water reabsorption 12
    56. 56. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin)  regulation of water reabsorption – aldosterone  12
    57. 57. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin)  regulation of water reabsorption – aldosterone  • ↑ Na+ retention 12
    58. 58. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin)  regulation of water reabsorption – aldosterone  • ↑ Na+ retention • ↑ K+ excretion 12
    59. 59. Hormone overview: • Any hormone that affects average systemic BP  effects on GFR: especially Ang II • 3 hormones  selective effects on the kidneys: – antidiuretic hormone (ADH, vasopressin)  regulation of water reabsorption – aldosterone  • ↑ Na+ retention • ↑ K+ excretion – atrial natriuretic peptide (ANP) opposite effects to aldosterone 12
    60. 60. Remember diuresis to remember antiduresis ADH naming 13
    61. 61. Remember diuresis to remember antiduresis ADH naming • ADH = anti-diuretic hormone 13
    62. 62. Remember diuresis to remember antiduresis ADH naming • ADH = anti-diuretic hormone • diuresis is a condition 13
    63. 63. Remember diuresis to remember antiduresis ADH naming • ADH = anti-diuretic hormone • diuresis is a condition  ↑ volume of dilute urine 13
    64. 64. Remember diuresis to remember antiduresis ADH naming • ADH = anti-diuretic hormone • diuresis is a condition  ↑ volume of dilute urine • ADH at physiological concentrations prevents diuresis 13
    65. 65. Remember diuresis to remember antiduresis ADH naming • ADH = anti-diuretic hormone • diuresis is a condition  ↑ volume of dilute urine • ADH at physiological concentrations prevents diuresis • “vasopressin” describes an “emergency” action at unphysiological LARGE concentrations of ADH 13
    66. 66. ADH mechanism of action 14
    67. 67. ADH mechanism of action  ↑ water permeability of collecting tubules 14
    68. 68. ADH mechanism of action  ↑ water permeability of collecting tubules  ↑ passive diffusion of water (“osmosis”) due to the concentration of NaCl in the ECF of the medulla of the kidney 14
    69. 69. ADH mechanism of action  ↑ water permeability of collecting tubules  ↑ passive diffusion of water (“osmosis”) due to the concentration of NaCl in the ECF of the medulla of the kidney  ↑ net water reabsorption from kidneys  ↓ osmotic pressure of plasma and ECF 14
    70. 70. Regulation of ADH 15
    71. 71. Regulation of ADH • ↑ osmotic pressure  “osmoreceptors” of the hypothalamus with no blood- brain barrier 15
    72. 72. Regulation of ADH • ↑ osmotic pressure  “osmoreceptors” of the hypothalamus with no blood- brain barrier • The osmoreceptors: 15
    73. 73. Regulation of ADH • ↑ osmotic pressure  “osmoreceptors” of the hypothalamus with no blood- brain barrier • The osmoreceptors: are close to the cell bodies that synthesize ADH 15
    74. 74. Regulation of ADH • ↑ osmotic pressure  “osmoreceptors” of the hypothalamus with no blood- brain barrier • The osmoreceptors: are close to the cell bodies that synthesize ADH  ↑ ADH secretion from pituitary 15
    75. 75. Regulation of ADH • ↑ osmotic pressure  “osmoreceptors” of the hypothalamus with no blood- brain barrier • The osmoreceptors: are close to the cell bodies that synthesize ADH  ↑ ADH secretion from pituitary • [negative feedback for regulation of osmotic pressure via a neurohormone] 15
    76. 76. 16
    77. 77. 17
    78. 78. Aldosterone 18
    79. 79. Aldosterone • Aldosterone acts on cells of the distal tubules  18
    80. 80. Aldosterone • Aldosterone acts on cells of the distal tubules  ↑ K+ excretion 18
    81. 81. Aldosterone • Aldosterone acts on cells of the distal tubules  ↑ K+ excretion ↑ Na+ retention 18
    82. 82. Aldosterone • Aldosterone acts on cells of the distal tubules  ↑ K+ excretion ↑ Na+ retention • Aldosterone is secreted by cells of the adrenal cortex in response to: 18
    83. 83. Aldosterone • Aldosterone acts on cells of the distal tubules  ↑ K+ excretion ↑ Na+ retention • Aldosterone is secreted by cells of the adrenal cortex in response to: ↑ [K+] or chronically ↓ [Na+] 18
    84. 84. Aldosterone • Aldosterone acts on cells of the distal tubules  ↑ K+ excretion ↑ Na+ retention • Aldosterone is secreted by cells of the adrenal cortex in response to: ↑ [K+] or chronically ↓ [Na+] ↑ Ang II 18
    85. 85. Negative FB for K + 19
    86. 86. Renin-angiotensin system 20
    87. 87. Renin-angiotensin system An example of a regulatory cascade: 20
    88. 88. Renin-angiotensin system An example of a regulatory cascade: Liver  Angiotensinogen in blood plasma 20
    89. 89. Renin-angiotensin system An example of a regulatory cascade: Liver  Angiotensinogen in blood plasma JG cells of afferent arterioles  renin 20
    90. 90. Renin-angiotensin system An example of a regulatory cascade: Liver  Angiotensinogen in blood plasma JG cells of afferent arterioles  renin Renin cleaves angiotensinogen  Ang I 20
    91. 91. Renin-angiotensin system An example of a regulatory cascade: Liver  Angiotensinogen in blood plasma JG cells of afferent arterioles  renin Renin cleaves angiotensinogen  Ang I Angiotensin converting enzyme (ACE) from endothelial cells cleaves Ang I  Ang II 20
    92. 92. Ang II actions 21
    93. 93. Ang II actions • Ang II is a powerful vasoconstrictor 21
    94. 94. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla 21
    95. 95. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla – both work together  ↑ BP 21
    96. 96. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla – both work together  ↑ BP • Ang II stimulates ↑ aldosterone secretion 21
    97. 97. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla – both work together  ↑ BP • Ang II stimulates ↑ aldosterone secretion –  ↑ Na+ reabsorption in the distal tubules 21
    98. 98. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla – both work together  ↑ BP • Ang II stimulates ↑ aldosterone secretion –  ↑ Na+ reabsorption in the distal tubules – and ↑ K+ excretion 21
    99. 99. Ang II actions • Ang II is a powerful vasoconstrictor – Ang II also “resets” the sensitivity of the CV regulatory region in the RF of the medulla – both work together  ↑ BP • Ang II stimulates ↑ aldosterone secretion –  ↑ Na+ reabsorption in the distal tubules – and ↑ K+ excretion • Ang II acts in the hypothalamus  thirst 21
    100. 100. ↓ renal BP  ↑ renin 22
    101. 101. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  22
    102. 102. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  ↑ renin 22
    103. 103. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  ↑ renin 2. baroreceptor reflex  ↑ sympathetic NS 22
    104. 104. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  ↑ renin 2. baroreceptor reflex  ↑ sympathetic NS  ↑ renin 22
    105. 105. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  ↑ renin 2. baroreceptor reflex  ↑ sympathetic NS  ↑ renin 3. ↓ nephron flow  ↓ tubuloglomerular 22
    106. 106. ↓ renal BP  ↑ renin 1.  direct stimulation of JG cells  ↑ renin 2. baroreceptor reflex  ↑ sympathetic NS  ↑ renin 3. ↓ nephron flow  ↓ tubuloglomerular  ↓ NO  ↑ renin 22
    107. 107. Hormone table Hormon Action Stimulu Type of e Source s s regulation Epi ADH Aldos Ang II 23
    108. 108. Integrated ECF regulation 24
    109. 109. Maintaining ECF 25
    110. 110. Maintaining ECF • Maintenance of the ECF operates on: 25
    111. 111. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) 25
    112. 112. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) – volume of water in plasma & ECF 25
    113. 113. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) – volume of water in plasma & ECF • Regulation of plasma and ECF composition depends mainly on: 25
    114. 114. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) – volume of water in plasma & ECF • Regulation of plasma and ECF composition depends mainly on: – kidneys 25
    115. 115. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) – volume of water in plasma & ECF • Regulation of plasma and ECF composition depends mainly on: – kidneys – but also, thirst 25
    116. 116. Maintaining ECF • Maintenance of the ECF operates on: – concentrations of electrolytes (& water) – volume of water in plasma & ECF • Regulation of plasma and ECF composition depends mainly on: – kidneys – but also, thirst • Emergency conditions also involve the cardiovascular system. 25
    117. 117. Regulation involved 26
    118. 118. Regulation involved • Renal regulation involves a number of hormonal and paracrine mechanisms, 26
    119. 119. Regulation involved • Renal regulation involves a number of hormonal and paracrine mechanisms, – and is therefore somewhat slow (minutes). 26
    120. 120. Regulation involved • Renal regulation involves a number of hormonal and paracrine mechanisms, – and is therefore somewhat slow (minutes). • Cardiovascular reflexes respond to some of the same hormones, 26
    121. 121. Regulation involved • Renal regulation involves a number of hormonal and paracrine mechanisms, – and is therefore somewhat slow (minutes). • Cardiovascular reflexes respond to some of the same hormones, – but also are exquisitely responsive to NS commands; 26
    122. 122. Regulation involved • Renal regulation involves a number of hormonal and paracrine mechanisms, – and is therefore somewhat slow (minutes). • Cardiovascular reflexes respond to some of the same hormones, – but also are exquisitely responsive to NS commands; – fast (seconds) 26
    123. 123. 27
    124. 124. Shock 28
    125. 125. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: 28
    126. 126. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: – ↓ BP 28
    127. 127. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: – ↓ BP – HR often ↑ (especially in hypovolemic) 28
    128. 128. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: – ↓ BP – HR often ↑ (especially in hypovolemic) • It is named by its cause. (“cardiogenic”, “hypovolemic”, etc.) 28
    129. 129. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: – ↓ BP – HR often ↑ (especially in hypovolemic) • It is named by its cause. (“cardiogenic”, “hypovolemic”, etc.) • It can be life threatening because ↓ CO  ↓ tissue perfusion and damage. 28
    130. 130. Shock • Clinically, shock describes a condition in which the cardiovascular system is failing: – ↓ BP – HR often ↑ (especially in hypovolemic) • It is named by its cause. (“cardiogenic”, “hypovolemic”, etc.) • It can be life threatening because ↓ CO  ↓ tissue perfusion and damage. 28 –  dangerous positive feedback

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