Ang II actions
1

Ang II actions
• Ang II is a powerful vasoconstrictor
1

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
1

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
1

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 - half done by potassium,
half done by Ang II
1

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 - half done by potassium,
half done by Ang II
–  ↑ Na+ reabsorption in the distal tubules
1

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 - half done by potassium,
half done by Ang II
–  ↑ Na+ reabsorption in the distal tubules
– and ↑ K+ excretion
1

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 - half done by potassium,
half done by Ang II
–  ↑ Na+ reabsorption in the distal tubules
– and ↑ K+ excretion
• Ang II acts in the hypothalamus  1

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
1.  direct stimulation of JG cells by ↓
blood flow  ↑ renin
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
1.  direct stimulation of JG cells by ↓
blood flow  ↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
1.  direct stimulation of JG cells by ↓
blood flow  ↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
 ↑ renin
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
1.  direct stimulation of JG cells by ↓
blood flow  ↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
 ↑ renin
3. ↓ nephron flow  ↓
tubuloglomerular
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Rate limiting step is amt of renin
↓ renal BP  ↑ renin
1.  direct stimulation of JG cells by ↓
blood flow  ↑ renin
2. baroreceptor reflex  ↑ sympathetic
NS
 ↑ renin
3. ↓ nephron flow  ↓
tubuloglomerular
 ↓ NO  ↑ renin
Renin and angiotensin II are very important
because there are three different ways of 2
getting it

Hormone table
Hormon Action Stimulu Type of
e Source s s regulation
Epi
ADH
Aldos
Ang II
3

Integrated ECF
Read part in the text book about this.
4

Maintaining ECF
5

Maintaining ECF
• Maintenance of the ECF operates on:
5

Maintaining ECF
• Maintenance of the ECF operates on:
– concentrations of electrolytes (& water)
5

Maintaining ECF
• Maintenance of the ECF operates on:
– concentrations of electrolytes (& water)
– volume of water in plasma & ECF
5

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:
5

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
5

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
5

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.
5

Regulation involved
6

Regulation involved
• Renal regulation involves a number of
hormonal and paracrine mechanisms,
6

Regulation involved
• Renal regulation involves a number of
hormonal and paracrine mechanisms,
– and is therefore somewhat slow
(minutes).
6

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,
6

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;
6

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)
6

Systems are integrated 7

Shock
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
– ↓ BP
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
– ↓ BP
– HR often ↑ (especially in hypovolemic)
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
– ↓ BP
– HR often ↑ (especially in hypovolemic)
• It is named by its cause.
(“cardiogenic”, “hypovolemic”, etc.)
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
– ↓ 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.
8

Shock
• Clinically, shock describes a condition
in which the cardiovascular system is
failing (and can’t keep up):
– ↓ 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.
–  dangerous positive feedback
8

Acid-Base Balance
9

many many acids are produced during
metabolism
The “problem”
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
– organic acids (lactic, etc.)
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
– organic acids (lactic, etc.)
– CO2
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
– organic acids (lactic, etc.)
– CO2
But normal pH in ECF is tightly
regulated:
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
– organic acids (lactic, etc.)
– CO2
But normal pH in ECF is tightly
regulated:
7.40 ± 0.02
10

many many acids are produced during
metabolism
The “problem”
metabolism  net production of acids
– organic acids (lactic, etc.)
– CO2
But normal pH in ECF is tightly
regulated:
7.40 ± 0.02
CSF and brain ECF are even more
precisely regulated.
10

3 methods of pH control
buffer capacity runs low quickly, major pH
change is problematic
Increases or decreases in ventilation changes
system pH
11

3 methods of pH control
1. buffering: mainly by HCO3- ions;
buffer capacity runs low quickly, major pH
also: change is problematic
Increases or decreases in ventilation changes
system pH
11

3 methods of pH control
1. buffering: mainly by HCO3- ions;
buffer capacity runs low quickly, major pH
also: change is problematic
– phosphate buffer system
Increases or decreases in ventilation changes
system pH
11

3 methods of pH control
1. buffering: mainly by HCO3- ions;
buffer capacity runs low quickly, major pH
also: change is problematic
– phosphate buffer system
– proteins
Increases or decreases in ventilation changes
system pH
11

3 methods of pH control
1. buffering: mainly by HCO3- ions;
buffer capacity runs low quickly, major pH
also: change is problematic
– phosphate buffer system
– proteins
2. respiration: rapid changes possible
through changes in ventilation 
CO2 Increases or decreases in ventilation changes
system pH
11

3 methods of pH control
1. buffering: mainly by HCO3- ions;
buffer capacity runs low quickly, major pH
also: change is problematic
– phosphate buffer system
– proteins
2. respiration: rapid changes possible
through changes in ventilation 
CO2 Increases or decreases in ventilation changes
system pH
3. kidney transport: actually a number
of different mechanisms, of which we
will focus on H+ and HCO - 11

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
carbonic anhydrase catalyzes 1st
step
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
carbonic anhydrase catalyzes 1st
step
• ↑ CO2 shifts the equilibrium “to the
right” 
↑ H+ and HCO3-
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
carbonic anhydrase catalyzes 1st
step
• ↑ CO2 shifts the equilibrium “to the
right” 
↑ H+ and HCO3-
Remember that ↑ CO2  ↑ H+ (roughly)
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
carbonic anhydrase catalyzes 1st
step
• ↑ CO2 shifts the equilibrium “to the
right” 
↑ H+ and HCO3-
Remember that ↑ CO2  ↑ H+ (roughly)
and therefore ↓ pH.
12

double check if we are being asked for H+ or
pH and are we giving the answer in the right
direction
Hydration of CO2
• CO2 is closely related to ventilation
equilibrium with H+ and HCO3-
carbonic anhydrase catalyzes 1st
step
• ↑ CO2 shifts the equilibrium “to the
right” 
↑ H+ and HCO3-
Remember that ↑ CO2  ↑ H+ (roughly)
and therefore ↓ pH.
• ↑ H+ combines with abundant HCO3-
to drive the equilibrium “to the left”  12

HCO3- buffering
13

HCO3- buffering
HCO3- is a useful buffer:
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
• works in the physiological range
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
• works in the physiological range
• can be adjusted by the:
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
• works in the physiological range
• can be adjusted by the:
– kidneys via both H+ and HCO3- regulation
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
• works in the physiological range
• can be adjusted by the:
– kidneys via both H+ and HCO3- regulation
– lungs indirectly via regulation of
ventilation
13

HCO3- buffering
HCO3- is a useful buffer:
• lots of HCO3- available
• works in the physiological range
• can be adjusted by the:
– kidneys via both H+ and HCO3- regulation
– lungs indirectly via regulation of
ventilation
• However, for relatively large changes,
the buffering mechanism is too 13

Respiratory changes
14

Respiratory changes
• Carbonic anhydrase in many tissues
catalyzes rapid hydration of CO2.
14

Respiratory changes
• Carbonic anhydrase in many tissues
catalyzes rapid hydration of CO2.
• CO2 is closely related to respiratory
exchange.
14

Respiratory changes
• Carbonic anhydrase in many tissues
catalyzes rapid hydration of CO2.
• CO2 is closely related to respiratory
exchange.
• Therefore, large shifts in respiration
14

Respiratory changes
• Carbonic anhydrase in many tissues
catalyzes rapid hydration of CO2.
• CO2 is closely related to respiratory
exchange.
• Therefore, large shifts in respiration
 changes in PCO2  pH changes :
14

Respiratory changes
• Carbonic anhydrase in many tissues
catalyzes rapid hydration of CO2.
• CO2 is closely related to respiratory
exchange.
• Therefore, large shifts in respiration
 changes in PCO2  pH changes :
termed respiratory changes in acid-
base balance.
14

Metabolic changes
15

Metabolic changes
• Altered metabolism may  ↑ amounts
of H+ (↓ pH).
15

Metabolic changes
• Altered metabolism may  ↑ amounts
of H+ (↓ pH).
• Also, loss of either ion may occur:
15

Metabolic changes
• Altered metabolism may  ↑ amounts
of H+ (↓ pH).
• Also, loss of either ion may occur:
– H+
15

Metabolic changes
• Altered metabolism may  ↑ amounts
of H+ (↓ pH).
• Also, loss of either ion may occur:
– H+
– HCO3-
15

Metabolic changes
• Altered metabolism may  ↑ amounts
of H+ (↓ pH).
• Also, loss of either ion may occur:
– H+
– HCO3-
termed metabolic changes in acid-
base balance
15

Henderson-Hasselbalch
equation
16

Henderson-Hasselbalch
equation
• The relationships among pH, HCO3-
and PCO2 are given by the equilibrium
equation for physiological conditions:
16

Henderson-Hasselbalch
equation
• The relationships among pH, HCO3-
and PCO2 are given by the equilibrium
equation for physiological conditions:
• pH = pK + log{[HCO3-] / α(PCO2)}
16

Henderson-Hasselbalch
equation
• The relationships among pH, HCO3-
and PCO2 are given by the equilibrium
equation for physiological conditions:
• pH = pK + log{[HCO3-] / α(PCO2)}
– pK = 6.1
16

Henderson-Hasselbalch
equation
• The relationships among pH, HCO3-
and PCO2 are given by the equilibrium
equation for physiological conditions:
• pH = pK + log{[HCO3-] / α(PCO2)}
– pK = 6.1
– α = 0.03
16

Acid-base disturbances
17

Acid-base disturbances
• Any combination of causes (metabolic
or respiratory) may occur with changes
in acid-base balance. (Table 20-2, p
670)
17

Acid-base disturbances
• Any combination of causes (metabolic
or respiratory) may occur with changes
in acid-base balance. (Table 20-2, p
670)
• Respiratory changes can be partially
compensated by renal adjustments.
17

Acid-base disturbances
• Any combination of causes (metabolic
or respiratory) may occur with changes
in acid-base balance. (Table 20-2, p
670)
• Respiratory changes can be partially
compensated by renal adjustments.
• Metabolic changes can be partially
compensated by both mechanisms :
17

Acid-base disturbances
• Any combination of causes (metabolic
or respiratory) may occur with changes
in acid-base balance. (Table 20-2, p
670)
• Respiratory changes can be partially
compensated by renal adjustments.
• Metabolic changes can be partially
compensated by both mechanisms :
– respiratory
17

Acid-base disturbances
• Any combination of causes (metabolic
or respiratory) may occur with changes
in acid-base balance. (Table 20-2, p
670)
• Respiratory changes can be partially
compensated by renal adjustments.
• Metabolic changes can be partially
compensated by both mechanisms :
– respiratory
– renal
17

Acid-base disturbances (2)
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
– or ↓ [HCO3-]
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
– or ↓ [HCO3-]
• Alkalosis refers to ↑ pH
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
– or ↓ [HCO3-]
• Alkalosis refers to ↑ pH
– ↓ [H+] production
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
– or ↓ [HCO3-]
• Alkalosis refers to ↑ pH
– ↓ [H+] production
– or ↑ [HCO3-]
18

Acid-base disturbances (2)
• Acidosis refers to a relative shift  ↓
pH
– ↑ [H+] production
– or ↓ [HCO3-]
• Alkalosis refers to ↑ pH
– ↓ [H+] production
– or ↑ [HCO3-]
• Complex combinations of effects may
occur over time with partial
compensation (renal and/or 18

Respiratory acidosis
19

Respiratory acidosis
• Cause: ↓ ventilation
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
– ↓ pH
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
– ↓ pH
– ↑ HCO3-
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
– ↓ pH
– ↑ HCO3-
• Compensation: renal (slow: hours -
days)
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
– ↓ pH
– ↑ HCO3-
• Compensation: renal (slow: hours -
days)
– ↑ excretion of H+
19

Respiratory acidosis
• Cause: ↓ ventilation
• Primary effect: ↑ PCO2
• Results: (equilibrium  R)
– ↓ pH
– ↑ HCO3-
• Compensation: renal (slow: hours -
days)
– ↑ excretion of H+
– ↑ retention of HCO3- 19

Respiratory alkalosis
20

Respiratory alkalosis
• Cause: ↑ ventilation
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
– ↑ pH
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
– ↑ pH
– ↓ HCO3-
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
– ↑ pH
– ↓ HCO3-
• Compensation: renal (slow)
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
– ↑ pH
– ↓ HCO3-
• Compensation: renal (slow)
– ↑ retention of H+
20

Respiratory alkalosis
• Cause: ↑ ventilation
• Primary effect: ↓ PCO2
• Results: (equilibrium  L)
– ↑ pH
– ↓ HCO3-
• Compensation: renal (slow)
– ↑ retention of H+
– ↑ excretion of HCO3-
20

[Aside: G.I. tract & H+/HCO3-]
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
leaving HCO3- in blood
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
leaving HCO3- in blood
Pancreas & duodenum secrete +++
HCO3- ,
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
leaving HCO3- in blood
Pancreas & duodenum secrete +++
HCO3- ,
but, the secretory process leaves H+ in
blood
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
leaving HCO3- in blood
Pancreas & duodenum secrete +++
HCO3- ,
but, the secretory process leaves H+ in
blood
Normally these activities  neutrality
over time.
21

[Aside: G.I. tract & H+/HCO3-]
Stomach secretes +++ H+,
leaving HCO3- in blood
Pancreas & duodenum secrete +++
HCO3- ,
but, the secretory process leaves H+ in
blood
Normally these activities  neutrality
over time.
HCO3- added to duodenum
neutralizes acid
ntering from
e 21

22

Metabolic acidosis
23

Metabolic acidosis
• Causes:
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
– or, ↓ HCO3- (usually via diarrhea)
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
– or, ↓ HCO3- (usually via diarrhea)
• Primary effect: ↑ H+
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
– or, ↓ HCO3- (usually via diarrhea)
• Primary effect: ↑ H+
• Results: (equilibrium  L)
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
– or, ↓ HCO3- (usually via diarrhea)
• Primary effect: ↑ H+
• Results: (equilibrium  L)
– ↓ pH
23

Metabolic acidosis
• Causes:
– ↑ production of H+ (diabetes mellitus)
– or, ↓ HCO3- (usually via diarrhea)
• Primary effect: ↑ H+
• Results: (equilibrium  L)
– ↓ pH
– ↓ HCO3-  hallmark feature
23

Metabolic acidosis (2)
24

Metabolic acidosis (2)
• Compensation: respiratory (fast: /
min)
24

Metabolic acidosis (2)
• Compensation: respiratory (fast: /
min)
– ↑ ventilation  ↑ loss of CO2 and H+
24

Metabolic acidosis (2)
• Compensation: respiratory (fast: /
min)
– ↑ ventilation  ↑ loss of CO2 and H+
• Compensation: renal (slow)
24

Metabolic acidosis (2)
• Compensation: respiratory (fast: /
min)
– ↑ ventilation  ↑ loss of CO2 and H+
• Compensation: renal (slow)
– ↑ excretion of H+
24

Metabolic acidosis (2)
• Compensation: respiratory (fast: /
min)
– ↑ ventilation  ↑ loss of CO2 and H+
• Compensation: renal (slow)
– ↑ excretion of H+
– ↑ retention of HCO3-
24

Metabolic alkalosis
25

Metabolic alkalosis
• Causes:
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
– ↑ HCO3- from antacids
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
– ↑ HCO3- from antacids
• Primary effect: ↑ pH and ↑ HCO3-
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
– ↑ HCO3- from antacids
• Primary effect: ↑ pH and ↑ HCO3-
• Results: (equilibrium  R)
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
– ↑ HCO3- from antacids
• Primary effect: ↑ pH and ↑ HCO3-
• Results: (equilibrium  R)
– ↑ pH
25

Metabolic alkalosis
• Causes:
– ↓ H+ due to vomiting
– ↑ HCO3- from antacids
• Primary effect: ↑ pH and ↑ HCO3-
• Results: (equilibrium  R)
– ↑ pH
– ↑ HCO3-  hallmark feature
25

Metabolic alkalosis (2)
26

Metabolic alkalosis (2)
• Compensation: respiratory (fast)
26

Metabolic alkalosis (2)
• Compensation: respiratory (fast)
– ↓ ventilation
26

Metabolic alkalosis (2)
• Compensation: respiratory (fast)
– ↓ ventilation
• Compensation: renal (slow)
26

Metabolic alkalosis (2)
• Compensation: respiratory (fast)
– ↓ ventilation
• Compensation: renal (slow)
– ↑ retention of H+
26

Metabolic alkalosis (2)
• Compensation: respiratory (fast)
– ↓ ventilation
• Compensation: renal (slow)
– ↑ retention of H+
– ↑ excretion of HCO3-
26

Regulation of Respiration
Generating a rhythmic pattern
for the skeletal muscles of
respiration
27

Special somatic motor process
28

Special somatic motor process
• This uses skeletal muscles:
28

Special somatic motor process
• This uses skeletal muscles:
– diaphragm
28

Special somatic motor process
• This uses skeletal muscles:
– diaphragm
– intercostal muscles (+ others)
28

Special somatic motor process
• This uses skeletal muscles:
– diaphragm
– intercostal muscles (+ others)
• At rest, only inhalation is active.
28

Special somatic motor process
• This uses skeletal muscles:
– diaphragm
– intercostal muscles (+ others)
• At rest, only inhalation is active.
exhalation depends on “elastic recoil”
28

Special somatic motor process
• This uses skeletal muscles:
– diaphragm
– intercostal muscles (+ others)
• At rest, only inhalation is active.
exhalation depends on “elastic recoil”
• Therefore, alternating bursts of AP
activity and “pauses”  α motor
neurons of these muscles.
28

29

Respiratory CPG’s
30

Respiratory CPG’s
• Neurons of the RF of the medulla
establish the basic rhythmic activity.
(CPG for resp)
30

Respiratory CPG’s
• Neurons of the RF of the medulla
establish the basic rhythmic activity.
(CPG for resp)
These partially overlap RF neurons that
regulate CV function.
30

Respiratory CPG’s
• Neurons of the RF of the medulla
establish the basic rhythmic activity.
(CPG for resp)
These partially overlap RF neurons that
regulate CV function.
• Other areas of the RF assist, including
neurons in the RF of the pons.
30

Phases of respiration
31

Phases of respiration
1. I phase: inspiration (inhalation)
31

Phases of respiration
1. I phase: inspiration (inhalation)
2. PI phase: post-inspiratory relaxation
of inspiratory muscles
31

Phases of respiration
1. I phase: inspiration (inhalation)
2. PI phase: post-inspiratory relaxation
of inspiratory muscles
3. E-2 phase: expiration (exhalation)
31

Simple model oscillator
32

Simple model oscillator
1. 2 populations of neurons:
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
– expiratory
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
– expiratory
2. Members of a given population are:
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
– expiratory
2. Members of a given population are:
– mutually excitatory (epsp’s)
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
– expiratory
2. Members of a given population are:
– mutually excitatory (epsp’s)
– inhibitory to other population (ipsp’s)
32

Simple model oscillator
1. 2 populations of neurons:
– inspiratory
– expiratory
2. Members of a given population are:
– mutually excitatory (epsp’s)
– inhibitory to other population (ipsp’s)
3. Depolarize spontaneously following
inhibition (or “pacemakers”?)
32

Oscillator function
33

Oscillator function
• Early active inspiratory neuron excites
others 
33

Oscillator function
• Early active inspiratory neuron excites
others 
– positive feedback burst of AP’s (I phase)
33

Oscillator function
• Early active inspiratory neuron excites
others 
– positive feedback burst of AP’s (I phase)
– inhibition of expiratory neurons
33

Oscillator function
• Early active inspiratory neuron excites
others 
– positive feedback burst of AP’s (I phase)
– inhibition of expiratory neurons
• Membrane properties limit duration
and frequency of inspiratory AP’s (PI
phase)
33

Oscillator function
• Early active inspiratory neuron excites
others 
– positive feedback burst of AP’s (I phase)
– inhibition of expiratory neurons
• Membrane properties limit duration
and frequency of inspiratory AP’s (PI
phase)
• Expiratory neurons “escape” inhibition
and fire their own burst. (E-2 phase)
33