This document discusses the regulation of nutrient levels in the bloodstream (plasma). It describes sensors like the pancreas and hypothalamus that detect plasma nutrient levels. It also describes effectors like hormones that are secreted to change the body's metabolic activity and maintain nutrient homeostasis, such as insulin promoting anabolism and glucagon promoting catabolism.

1. Sensors & effectors
1

2. Sensors & effectors
• For this type of regulation, sensors
detect plasma levels of nutrients. - For
example: glucose
1

3. Sensors & effectors
• For this type of regulation, sensors
detect plasma levels of nutrients. - For
example: glucose
– islets of Langerhans of the pancreas
1

4. Sensors & effectors
• For this type of regulation, sensors
detect plasma levels of nutrients. - For
example: glucose
– islets of Langerhans of the pancreas
– hypothalamus (certain cells)
1

5. Sensors & effectors
• For this type of regulation, sensors
detect plasma levels of nutrients. - For
example: glucose
– islets of Langerhans of the pancreas
– hypothalamus (certain cells)
• The same cells (or closely related
ones) change the secretory rate of a
hormone. - Cartoon (kinds of
metabolic activity) diagram
1

6. Sensors & effectors
• For this type of regulation, sensors
detect plasma levels of nutrients. - For
example: glucose
– islets of Langerhans of the pancreas
– hypothalamus (certain cells)
• The same cells (or closely related
ones) change the secretory rate of a
hormone. - Cartoon (kinds of
metabolic activity) diagram
• Many types of cells in the body are 1

7. 2

8. Anabolic state
Building stuff up
3

9. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
3

10. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
• glucose  glycogen
3

11. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
• glucose  glycogen
• fatty acids  triglyceride (“fat”)
3

12. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
• glucose  glycogen
• fatty acids  triglyceride (“fat”)
• amino acids  protein
3

13. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
• glucose  glycogen
• fatty acids  triglyceride (“fat”)
• amino acids  protein
3

14. Anabolic state
Building stuff up
High nutrient levels (after a meal) 
nutrient storage:
• glucose  glycogen
• fatty acids  triglyceride (“fat”)
• amino acids  protein
• Hormones alter cellular enzymatic
activities to regulate nutrient storage
& use 3

15. Catabolic state
pneumonic: cat’s tend to take things apart
4

16. Catabolic state
pneumonic: cat’s tend to take things apart
Between meals, or with high rates of
nutrient use, nutrient levels fall in
plasma.
4

17. Catabolic state
pneumonic: cat’s tend to take things apart
Between meals, or with high rates of
nutrient use, nutrient levels fall in
plasma.
• Stored nutrients are “mobilized” to
support blood levels of major
nutrients.
4

18. Catabolic state
pneumonic: cat’s tend to take things apart
Between meals, or with high rates of
nutrient use, nutrient levels fall in
plasma.
• Stored nutrients are “mobilized” to
support blood levels of major
nutrients.
4

19. Catabolic state
pneumonic: cat’s tend to take things apart
Between meals, or with high rates of
nutrient use, nutrient levels fall in
plasma.
• Stored nutrients are “mobilized” to
support blood levels of major
nutrients.
• A different pattern of hormones
regulates cellular target enzymes.
4

20. 5

21. Missing the slides on GI Portal Circulation -
however they are located at the end of 9A
Pancreatic hormones
regulate the balance of
nutrient storage and
mobilization
6

22. Gastro Portal System notes
• 1st capillaries collect:
• nutrients absorbed from intestine
(stomach)
• pancreatic hormones (especially
insulin)
also secreted during cephalic; gastric
phases
• mixing
7

23. GI Portal notes cont.
• 2nd capillaries target liver cells
• main target --> first place of nutrient
absorption
8

24. Insulin is anabolic
• source: Beta cells of the islets of
Langerhans in the pancreas
• major targets: liver, skeletal muscle,
adipose (most cells of the body
• target actions: nutriet storage
• glucose --> glycogen
• fatty acids --> triglyceride
• amino acids --> protein
9

25. Insulin mechanisms of action
• insulin --> glucose uptake by many
kinds of cells
• many actions on enzymes of glucose
utilization (especially in the liver)
10

26. Glucagon is catabolic
7

27. Glucagon is catabolic
• source: α cells of the pancreatic islets
7

28. Glucagon is catabolic
• source: α cells of the pancreatic islets
• major target: the liver
7

29. Glucagon is catabolic
• source: α cells of the pancreatic islets
• major target: the liver
• target action: glycogenolysis
7

30. Glucagon is catabolic
• source: α cells of the pancreatic islets
• major target: the liver
• target action: glycogenolysis
• stimulus for glucagon secretion:
7

31. Glucagon is catabolic
• source: α cells of the pancreatic islets
• major target: the liver
• target action: glycogenolysis
• stimulus for glucagon secretion:
↓ blood glucose (negative feedback)
7

32. Stimuli for insulin secretion
• In general, a meal --> insulin
secretion
– cephalic phase (via vagues) yields an
increase in insulin
– GI hormones --> increase in insulin
• gastrin
• CCk
• secretin
12

33. Glucagon cells around the periphery 8

34. It shows that there is gluconeogenesis - does not happen
physiologically (takes a lot more glycogen than usual to have this 9
during a fasting state).

35. 10

36. Other catabolic hormones
11

37. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
11

38. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
11

39. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
11

40. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
11

41. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
• [Cortisol  conversion of protein  ↑
BG
11

42. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
• [Cortisol  conversion of protein  ↑
BG
protective in chronic ↓ food intake, stress]
11

43. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
• [Cortisol  conversion of protein  ↑
BG
protective in chronic ↓ food intake, stress]
• [Growth hormone indirectly  ↑ BG
11

44. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
• [Cortisol  conversion of protein  ↑
BG
protective in chronic ↓ food intake, stress]
• [Growth hormone indirectly  ↑ BG
has “anti-insulin” actions]
11

45. Other catabolic hormones
• Epinephrine stimulates glycogenolysis
In coordination with its other actions,
Epi  ↑ BG for strenuous exercise
• blocks insulin (verify later)
• [Cortisol  conversion of protein  ↑
BG
protective in chronic ↓ food intake, stress]
• [Growth hormone indirectly  ↑ BG
has “anti-insulin” actions]
• causes peptides that compete with insulin 11

46. Why so many catabolic hormones?
12

47. Why so many catabolic hormones?
• Note the stimuli for secretion!
12

48. Why so many catabolic hormones?
• Note the stimuli for secretion!
• Differing physiological states have
separate regulation to ↑ BG
12

49. Abnormalities of glucose
regulation
13

50. Hypoglycemia
14

51. Hypoglycemia
• [a rare condition]
14

52. Hypoglycemia
• [a rare condition]
• Prolonged ↓ BG may be caused by an
insulin-secreting tumor.
14

53. Hypoglycemia
• [a rare condition]
• Prolonged ↓ BG may be caused by an
insulin-secreting tumor.
• Once thought to be caused by
prolonged insulin secretion following
a meal. (?)
14

54. Not enough glucose around
Diabetes mellitus symptoms
15

55. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
15

56. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
15

57. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
• glucose in the urine
15

58. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
• glucose in the urine
• abnormal metabolism (metabolic
acidosis)
15

59. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
• glucose in the urine
• abnormal metabolism (metabolic
acidosis)
• (↑ appetite)
15

60. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
• glucose in the urine
• abnormal metabolism (metabolic
acidosis)
• (↑ appetite)
• dehydration, fainting, shock G
15

61. Not enough glucose around
Diabetes mellitus symptoms
• ↑ BG
• diuresis
• glucose in the urine
• abnormal metabolism (metabolic
acidosis)
• (↑ appetite)
• dehydration, fainting, shock G
• ↓ immune function
15

62. Type I (insulin dependent)
16

63. Type I (insulin dependent)
• causes?
16

64. Type I (insulin dependent)
• causes?
– may follow a viral infection
16

65. Type I (insulin dependent)
• causes?
– may follow a viral infection
– autoimmune condition
16

66. Type I (insulin dependent)
• causes?
– may follow a viral infection
– autoimmune condition
• effects:
16

67. Type I (insulin dependent)
• causes?
– may follow a viral infection
– autoimmune condition
• effects:
– insulin lack
16

68. Type I (insulin dependent)
• causes?
– may follow a viral infection
– autoimmune condition
• effects:
– insulin lack
– abnormal metabolism  ketoacidosis
16

69. Type I (insulin dependent)
• causes?
– may follow a viral infection
– autoimmune condition
• effects:
– insulin lack
– abnormal metabolism  ketoacidosis
• treatment: administration of insulin
16

70. 17

71. Type II (insulin resistant)
18

72. Type II (insulin resistant)
• causes – reduced responses to insulin
18

73. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
18

74. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
18

75. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
18

76. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
• effects:
18

77. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
• effects:
– ↑ BG, ↑ insulin, (↑ glucagon)
18

78. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
• effects:
– ↑ BG, ↑ insulin, (↑ glucagon)
• treatment:
18

79. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
• effects:
– ↑ BG, ↑ insulin, (↑ glucagon)
• treatment:
– lifestyle
18

80. Type II (insulin resistant)
• causes – reduced responses to insulin
– a modern “epidemic”
– associated with obesity (link to adipose
stores)
– genetic / cultural
• effects:
– ↑ BG, ↑ insulin, (↑ glucagon)
• treatment:
– lifestyle
– drugs
18

81. Hypothalamus
Integrating center for
internal regulation
19

82. 20

83. Overview
21

84. Overview
• Sensors
21

85. Overview
• Sensors
– branches of many peripheral sensory
systems
21

86. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
21

87. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
• Effector systems
21

88. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
• Effector systems
– somatic motor systems
21

89. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
• Effector systems
– somatic motor systems
– autonomic nervous system
21

90. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
• Effector systems
– somatic motor systems
– autonomic nervous system
– hormonal regulation via the pituitary
gland
21

91. Overview
• Sensors
– branches of many peripheral sensory
systems
– intrinsic sensors for local conditions
• Effector systems
– somatic motor systems
– autonomic nervous system
– hormonal regulation via the pituitary
gland
• Site of integration for feedback 21

92. Temperature
regulation
22

93. Temperature regions
23

94. Temperature regions
• body “core”:
23

95. Temperature regions
• body “core”:
– deep within the body
23

96. Temperature regions
• body “core”:
– deep within the body
– best regulated (~98.6° F or ~37° C)
23

97. Temperature regions
• body “core”:
– deep within the body
– best regulated (~98.6° F or ~37° C)
– ex: brain, heart, deep abdominal
23

98. Temperature regions
• body “core”:
– deep within the body
– best regulated (~98.6° F or ~37° C)
– ex: brain, heart, deep abdominal
• surface temperatures vary
23

99. Temperature regions
• body “core”:
– deep within the body
– best regulated (~98.6° F or ~37° C)
– ex: brain, heart, deep abdominal
• surface temperatures vary
~85 – 95° F (or ~30 – 35° C)
23

100. Sensors
24

101. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
24

102. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
24

103. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
• cold receptors:
24

104. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
• cold receptors:
– most common
24

105. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
• cold receptors:
– most common
– ↑ AP frequency with ↓ temperature
24

106. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
• cold receptors:
– most common
– ↑ AP frequency with ↓ temperature
• warm receptors ↑ AP frequency with ↑ temp
24

107. Sensors
Peripheral receptors are most active for
temperatures outside ~ 85 - 95° F.
• They signal changes best (significant
adaptation).
• cold receptors:
– most common
– ↑ AP frequency with ↓ temperature
• warm receptors ↑ AP frequency with ↑ temp
• relative # of active neurons  perceived temp
24

108. 25

109. Sensors (2)
26

110. Sensors (2)
Several locations within the CNS also
have neurons that ↑ activity in
response to temperature changes
(“central” receptors).
26

111. Sensors (2)
Several locations within the CNS also
have neurons that ↑ activity in
response to temperature changes
(“central” receptors).
• Warming or cooling of regions of the
hypothalamus  changes in activity
here.
26

112. Sensors (2)
Several locations within the CNS also
have neurons that ↑ activity in
response to temperature changes
(“central” receptors).
• Warming or cooling of regions of the
hypothalamus  changes in activity
here.
• These neurons are highly sensitive to
changes of only a fraction of a ° C.
26

113. Sensors (2)
Several locations within the CNS also
have neurons that ↑ activity in
response to temperature changes
(“central” receptors).
• Warming or cooling of regions of the
hypothalamus  changes in activity
here.
• These neurons are highly sensitive to
changes of only a fraction of a ° C.
• The hypothalamus integrates central
and (peripheral) temperatures. 26

114. Effectors: Heat gain & loss
27

115. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
27

116. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
usually warmer than the environment (Ta)
27

117. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
usually warmer than the environment (Ta)
• At steady state,
27

118. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
usually warmer than the environment (Ta)
• At steady state,
total heat gain = total heat loss
27

119. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
usually warmer than the environment (Ta)
• At steady state,
total heat gain = total heat loss
• Many of the mechanisms of heat gain
and heat loss are controllable,
27

120. Effectors: Heat gain & loss
• At steady state, body temperature (Tb)
is ~37° C (~98.6 ° F);
usually warmer than the environment (Ta)
• At steady state,
total heat gain = total heat loss
• Many of the mechanisms of heat gain
and heat loss are controllable,
therefore can be used for regulation.
27

121. External heat exchange
28

122. External heat exchange
4 physical processes exchange heat:
28

123. External heat exchange
4 physical processes exchange heat:
• radiation: heat transfer through
infrared and other wavelengths
28

124. External heat exchange
4 physical processes exchange heat:
• radiation: heat transfer through
infrared and other wavelengths
• conduction: heat transfer through
contact
28

125. External heat exchange
4 physical processes exchange heat:
• radiation: heat transfer through
infrared and other wavelengths
• conduction: heat transfer through
contact
• convection: heat transfer through air
movement
28

126. External heat exchange
4 physical processes exchange heat:
• radiation: heat transfer through
infrared and other wavelengths
• conduction: heat transfer through
contact
• convection: heat transfer through air
movement
• evaporation: cooling through the
conversion of liquid water to water
vapor 28

127. 29

128. Internal heat production
30

129. Internal heat production
• general cellular metabolism (including,
“basal” heat production)
30

130. Internal heat production
• general cellular metabolism (including,
“basal” heat production)
• skeletal muscle contraction (including,
shivering)
30

131. Internal heat production
• general cellular metabolism (including,
“basal” heat production)
• skeletal muscle contraction (including,
shivering)
• [brown adipose tissue in infant
mammals, and true hibernators]
30

132. Behavior
Most vertebrates (not just mammals) are
adept at using behavior to assist in
temperature regulation.
31

133. 32

134. 33

135. 34

136. 35

137. 36

138. 37

139. Working to regulate
38

140. Working to regulate
• When Ta is between ~27.8 - 30° C
basal metabolic processes provide
enough heat to maintain the 37 ° Tb.
38

141. Working to regulate
• When Ta is between ~27.8 - 30° C
basal metabolic processes provide
enough heat to maintain the 37 ° Tb.
• Outside that narrow range (both
warmer and cooler), physiological
mechanisms in addition to behavior
consume more metabolic energy to
maintain Tb.
38

142. Effector processes
39

143. Effector processes
• Behavior! (many activities;
telokinetic)
39

144. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
39

145. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
– vasoconstriction: ↓ heat loss
39

146. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
– vasoconstriction: ↓ heat loss
– vasodilation: ↑ heat loss
39

147. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
– vasoconstriction: ↓ heat loss
– vasodilation: ↑ heat loss
– postganglionic sympathetic neurons w
ACh
39

148. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
– vasoconstriction: ↓ heat loss
– vasodilation: ↑ heat loss
– postganglionic sympathetic neurons w
ACh
– arteriovenous anastomoses bypass
surface capillaries (↓ heat loss)
39

149. Effector processes
• Behavior! (many activities;
telokinetic)
• Cutaneous blood flow
– vasoconstriction: ↓ heat loss
– vasodilation: ↑ heat loss
– postganglionic sympathetic neurons w
ACh
– arteriovenous anastomoses bypass
surface capillaries (↓ heat loss)
• Sweating ( evaporative cooling; 39

150. Effector processes (2)
40

151. Effector processes (2)
• Shivering: rhythmic contractions of
particular muscle groups (somatic
motor)
40

152. Effector processes (2)
• Shivering: rhythmic contractions of
particular muscle groups (somatic
motor)
• Nonshivering thermogenesis:
(general metabolic processes; via
hormones in adults)
40

153. Hypothalamus
41

154. Hypothalamus
• The hypothalamus acts as a closed
loop negative feedback temperature
controller.
41

155. Hypothalamus
• The hypothalamus acts as a closed
loop negative feedback temperature
controller.
– Heating the hypothalamus  integrated
heat loss responses.
41

156. Hypothalamus
• The hypothalamus acts as a closed
loop negative feedback temperature
controller.
– Heating the hypothalamus  integrated
heat loss responses.
– Cooling the hypothalamus  integrated
heat gain responses.
41

157. Hypothalamus
• The hypothalamus acts as a closed
loop negative feedback temperature
controller.
– Heating the hypothalamus  integrated
heat loss responses.
– Cooling the hypothalamus  integrated
heat gain responses.
• Under physiological conditions,
(surface) and hypothalamic
temperature are integrated. 41

158. 42

159. Feldberg’s cats
43

160. Feldberg’s cats
• Chronic cannulation of the cerebral ventricles
permits infusion of transmitters / drugs that
“bypass” the blood-brain barrier systems to
reach brain neurons via CSF.
43

161. Feldberg’s cats
• Chronic cannulation of the cerebral ventricles
permits infusion of transmitters / drugs that
“bypass” the blood-brain barrier systems to
reach brain neurons via CSF.
• If NE or serotonin (5-HT) reach the
hypothalamus  integrated thermoregulation:
43

162. Feldberg’s cats
• Chronic cannulation of the cerebral ventricles
permits infusion of transmitters / drugs that
“bypass” the blood-brain barrier systems to
reach brain neurons via CSF.
• If NE or serotonin (5-HT) reach the
hypothalamus  integrated thermoregulation:
– NE  heat loss responses
43

163. Feldberg’s cats
• Chronic cannulation of the cerebral ventricles
permits infusion of transmitters / drugs that
“bypass” the blood-brain barrier systems to
reach brain neurons via CSF.
• If NE or serotonin (5-HT) reach the
hypothalamus  integrated thermoregulation:
– NE  heat loss responses
– 5-HT  heat gain responses
43

164. Feldberg’s cats
• Chronic cannulation of the cerebral ventricles
permits infusion of transmitters / drugs that
“bypass” the blood-brain barrier systems to
reach brain neurons via CSF.
• If NE or serotonin (5-HT) reach the
hypothalamus  integrated thermoregulation:
– NE  heat loss responses
– 5-HT  heat gain responses
• Normal temperature is a balance of NE / 5-HT
43

165. Fever
44

166. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
44

167. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
• Infection, inflammation  regulatory cascade
that  this resetting.
44

168. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
• Infection, inflammation  regulatory cascade
that  this resetting.
• Cytokines  prostaglandin (PG) synthesis
(hypothalamus)
44

169. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
• Infection, inflammation  regulatory cascade
that  this resetting.
• Cytokines  prostaglandin (PG) synthesis
(hypothalamus)
 ↑ 5-HT  heat gain responses
44

170. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
• Infection, inflammation  regulatory cascade
that  this resetting.
• Cytokines  prostaglandin (PG) synthesis
(hypothalamus)
 ↑ 5-HT  heat gain responses
 new, higher Tb
44

171. Fever
• Fever is a resetting of the “thermostat” to a
higher set point. (allostatic adjustment)
• Infection, inflammation  regulatory cascade
that  this resetting.
• Cytokines  prostaglandin (PG) synthesis
(hypothalamus)
 ↑ 5-HT  heat gain responses
 new, higher Tb
• Thermoregulation will then take place around
this new set point.
44

172. Drugs that reduce fever
45

173. Drugs that reduce fever
• PG synthesis requires an initial
enzyme, cyclooxygenase (COX)
45

174. Drugs that reduce fever
• PG synthesis requires an initial
enzyme, cyclooxygenase (COX)
• Drugs that reduce fever vary widely,
45

175. Drugs that reduce fever
• PG synthesis requires an initial
enzyme, cyclooxygenase (COX)
• Drugs that reduce fever vary widely,
but all inhibit this particular COX.
45

176. Drugs that reduce fever
• PG synthesis requires an initial
enzyme, cyclooxygenase (COX)
• Drugs that reduce fever vary widely,
but all inhibit this particular COX.
• Thus, the ↑ 5-HT is prevented,
blocking the final steps in the fever
“cascade”.
45