1. Renal regulation
Regulation of the
volume and composition
of extracellular fluid (ECF)
1

2. Overview
Text
2

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

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

5. Overview
• What is regulated for
ECF: (outputs)
– water
– Na+
Text
2

6. Overview
• What is regulated for
ECF: (outputs)
– water
– Na+
– K+ Text
2

7. Overview
• What is regulated for
ECF: (outputs)
– water
– Na+
– K+ Text
– other solutes (glucose,
amino acids, etc.)
2

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. 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. 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. 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. 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. 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. Regulation of glomerular
filtration
3

15. As BP goes up, glomerular filtration goes
up 4

16. Keep a list of autoregulation
Autoregulation
5

17. Keep a list of autoregulation
Autoregulation
Apart from neural regulation, there are
2 ways that the kidneys “self-
regulate”.
5

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. 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. Myogenic autoregulation
6

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

22. Myogenic autoregulation
• Arteriolar smooth muscle responds to
stretch like other muscles – by
contracting.
• Therefore, ↑ BP  ↑ stretch 
6

23. Myogenic autoregulation
• Arteriolar smooth muscle responds to
stretch like other muscles – by
contracting.
• Therefore, ↑ BP  ↑ stretch 
↑ contraction  ↓ filtration pressure
6

24. Myogenic autoregulation
• Arteriolar smooth muscle responds to
stretch like other muscles – by
contracting.
• Therefore, ↑ BP  ↑ stretch 
↑ contraction  ↓ filtration pressure
 ↓ GFR (constant)
6

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. 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. Tubuloglomerular Feedback
7

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

29. Tubuloglomerular Feedback
• This effect depends on special
structure – the juxtaglomerular
apparatus.
• macula densa cells of the distal
convoluted tubule (the sensor)
7

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. 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. 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. 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. 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. 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. 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. 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. Sympathetic nerves
9

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

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

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

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. 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. Sympathetic nerves (2)
10

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

46. Sympathetic nerves (2)
• Vasoconstriction of the afferent
arteriole  ↓ blood flow & ↓ GFR
• Constricting the efferent arterioles 
↑ filtration pressure & ↑ GFR
10

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. 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. Hormonal regulation
mainly, effects on the
movement of specific
substances
11

50. Hormone overview:
12

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

52. Hormone overview:
• Any hormone that affects average systemic BP
 effects on GFR:
especially Ang II
12

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. 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. 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. 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. 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. 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. 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. Remember diuresis to remember antiduresis
ADH naming
13

61. Remember diuresis to remember antiduresis
ADH naming
• ADH = anti-diuretic hormone
13

62. Remember diuresis to remember antiduresis
ADH naming
• ADH = anti-diuretic hormone
• diuresis is a condition
13

63. Remember diuresis to remember antiduresis
ADH naming
• ADH = anti-diuretic hormone
• diuresis is a condition
 ↑ volume of dilute urine
13

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. 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. ADH mechanism of action
14

67. ADH mechanism of action
 ↑ water permeability of collecting
tubules
14

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. 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. Regulation of ADH
15

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

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

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. 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. 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. 16

77. 17

78. Aldosterone
18

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

80. Aldosterone
• Aldosterone acts on cells of the distal
tubules 
↑ K+ excretion
18

81. Aldosterone
• Aldosterone acts on cells of the distal
tubules 
↑ K+ excretion
↑ Na+ retention
18

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. 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. 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. Negative FB for K +
19

86. Renin-angiotensin system
20

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

88. Renin-angiotensin system
An example of a regulatory cascade:
Liver  Angiotensinogen in blood
plasma
20

89. Renin-angiotensin system
An example of a regulatory cascade:
Liver  Angiotensinogen in blood
plasma
JG cells of afferent arterioles  renin
20

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. 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. Ang II actions
21

93. Ang II actions
• Ang II is a powerful vasoconstrictor
21

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. 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. 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. 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. 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. 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. ↓ renal BP  ↑ renin
22

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

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

103. ↓ renal BP  ↑ renin
1.  direct stimulation of JG cells 
↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
22

104. ↓ renal BP  ↑ renin
1.  direct stimulation of JG cells 
↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
 ↑ renin
22

105. ↓ renal BP  ↑ renin
1.  direct stimulation of JG cells 
↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
 ↑ renin
3. ↓ nephron flow  ↓
tubuloglomerular
22

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. Hormone table
Hormon Action Stimulu Type of
e Source s s regulation
Epi
ADH
Aldos
Ang II
23

108. Integrated ECF regulation
24

109. Maintaining ECF
25

110. Maintaining ECF
• Maintenance of the ECF operates on:
25

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

112. Maintaining ECF
• Maintenance of the ECF operates on:
– concentrations of electrolytes (& water)
– volume of water in plasma & ECF
25

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. 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. 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. 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. Regulation involved
26

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

119. Regulation involved
• Renal regulation involves a number of
hormonal and paracrine mechanisms,
– and is therefore somewhat slow
(minutes).
26

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. 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. 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. 27

124. Shock
28

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

126. Shock
• Clinically, shock describes a
condition in which the
cardiovascular system is failing:
– ↓ BP
28

127. Shock
• Clinically, shock describes a
condition in which the
cardiovascular system is failing:
– ↓ BP
– HR often ↑ (especially in hypovolemic)
28

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. 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. 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