Cardiovascular and Respiratory
Systems: Getting Oxygen From
Air to Muscle
Integration of Ventilation, Heart,
and Circulation
Cardiorespiratory System
Functions of cardiorespiratory system:
 transportation of O2 and CO2
 transportation of nutrients/waste products
 distribution of hormones
 thermoregulation
 maintenance of blood pressure
Ability of
cardiorespiratory
system to maintain high
arterial oxygen levels
(PaO2) during graded
exercise to exhaustion
Critical elements of O2 Transport Pathway
 Ventilation
– Moving air in/out of lungs
 External respiration
– Gas exchange between alveoli and blood
 Heart and circulation
 O2 diffusion into mitochondria
Role of the Heart
Moving O2 from lungs to muscle
Oxygen Delivery Determines VO2
(Fick Principle)
VO2 = Q  (CaO2 – CvO2)
VO2 = [HR  SV]  (CaO2 – CvO2)
VO2 = [BP  TPR]  (CaO2 – CvO2)
Cardiac Cycle
 systole  diastole
 cardiac output (Q) = stroke volume (SV) 
heart rate (HR)
examples
– rest: SV = 75 ml; HR = 60 bpm; Q = 4.5 Lmin-1
– exercise: SV = 130 ml; HR = 180 bpm; Q = 23.4 Lmin-1
Cardiac output affected by:
1. preload – end diastolic pressure
(amount of myocardial stretch)
2. afterload – resistance blood
encounters as it leaves ventricles
3. contractility – strength of cardiac
contraction
4. heart rate
Muscle pump and
one-way valves
assist venous
return
Cardiac Output Regulation
Extrinsic control
 autonomic nervous
system
– sympathetic NS (1
control at HR >100 bpm)
• NE released as neural
transmitter
– parasympathetic NS (1
control at HR <100 bpm)
• ACh released as neural
transmitter
 hormonal
– EPI, NE
Ventilation and External
Respiration
Getting O2 from air into blood
A. Major
pulmonary
structures
B. General view
showing alveoli
and blood
vessels
C. Section of
lung showing
individual alveoli
D. Pulmonary
capillaries
surrounding
alveolar walls
Single alveoli at rest
showing individual RBCs
RBC
Single alveoli under high flow
showing increased RBCs
Lungs and Pulmonary Circulation
 alveolar membrane thickness is ~ 0.1 µm
 total alveolar surface area is ~75 m2
 80-90% of alveoli are covered by
capillaries
 pulmonary circulation varies with cardiac
output and matched to ventilation rate
Gases Move Down Pressure Gradients
O2 and CO2 transit time
in lungs (left) and tissue (right) at rest
Notice rapid saturation with O2 by the time RBCs have
traveled ⅓ around alveolus
PO2 in blood returning to the lungs is
____ PO2 in the alveoli.
A. greater than
B. less than
C. similar to
PO2 in arterial blood is ____ PO2 in the
mitochondria.
A. greater than
B. less than
C. similar to
PCO2 in venous blood is ____ PCO2 in
the alveoli.
A. greater than
B. less than
C. similar to
What would be the effect on the saturation of
arterial blood with O2 (SaO2) when pulmonary
blood flow is faster than the diffusion rate of O2?
A. SaO2 would remain unchanged
B. SaO2 would be decreased
C. SaO2 would be increased
Rate of gas diffusion is dependent
upon pressure (concentration)
gradient.
Erythrocyte (RBC)
 ~98% of O2 is bound up with
hemoglobin (Hb)
Hb consists of four O2-binding
heme (iron containing) molecules
combines reversibly w/ O2 (forms
oxy-hemoglobin)
1-2% of O2 is dissolved in plasma
Transport of CO2 in blood
~75%
~5%
~20%
CO2 + H2O  H2CO3  H+ + HCO3-
Oxygen is transported from lungs to
muscle primarily
A. dissolved in blood.
B. bound to hemoglobin.
C. as a bicarbonate ion.
Carbon dioxide is transported from
muscle to the lungs
A.
B.
C.
D.
dissolved in blood.
bound to hemoglobin.
as a bicarbonate ion.
all of the above are transport
mechanisms for CO2
Ventilatory Response to Exercise
and Control of Blood pH
Minute ventilation (VE) response to different exercise intensities
Ventilatory Control Mechanisms
Current thought is that
primary control of
ventilation is:
• from muscle afferents
sensory inputs
• to control arterial
PCO2,(peripheral
PCO2
chemoreceptors)
• to minimize  in blood
pH (peripheral pH
chemoreceptors)
Ventilatory responses to incremental exercise
VE vs VO2
5
200
4.5
180
4
160
3.5
140
VE (L/min)
VCO2 (L/min)
VCO2 vs VO2
3
2.5
2
120
100
80
1.5
60
1
40
0.5
20
0
0
0
1
2
3
VO2 (L/min)
4
5
6
0
1
2
3
4
5
6
VO2 (L/min)
Why are there a breakpoints in the linearity of VE and VCO2?
7
Ventilatory Regulation of Acid-Base
Balance
CO2 + H2O  H2CO3  H+ + HCO3 at low-intensity exercise, source of CO2 is entirely from
substrate metabolism
 bicarbonate (HCO3-) buffers H+ produced during highintensity exercise
 at high-intensity exercise, bicarbonate ions also
contribute to CO2 production
– source of CO2 is from substrates and bicarbonate ions (HCO3-)
  blood [H+] stimulates VE to rid excess CO2 (and H+)
Can RER ever exceed 1.0? When? Explain
Lactate (mM)
Blood Lactate
12
10
8
6
4
2
0
50
100
150
200
250
Treadmill Speed (m/min)
300
350
Blood pH
7.45
7.40
7.35
pH
7.30
7.25
7.20
7.15
7.10
7.05
4
5
6
7
8
9
10
11
12
Treadmill Speed (mph)
13
14
15
Respiratory Exchange Ratio
1.3
RER
1.2
1.1
1.0
RER = VCO2
VO2
0.9
0.8
4
5
6
7
8
9
10
11
12
Treadmill Speed (mph)
13
14
15
CO2 Production
90
VCO2 (ml/kg/min)
80
70
60
50
40
30
20
10
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Treadmill Speed (mph)
Minute Ventilation
Minute Ventilation (L/min)
200
180
160
140
120
100
80
60
40
20
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Treadmill Speed (mph)
VE vs VO2
5
200
4.5
180
4
160
3.5
140
VE (L/min)
VCO2 (L/min)
VCO2 vs VO2
3
2.5
2
120
100
80
1.5
60
1
40
0.5
20
0
0
0
1
2
3
VO2 (L/min)
4
5
6
0
1
2
3
4
5
VO2 (L/min)
What is the primary cause of hyperventilation
during incremental exercise?
A.
B.
C.
D.
E.
muscles cannot get enough O2
sympathetic innervation
accumulation of lactate ions in blood
conscious desire to breath harder
additional stimulation of PCO2 chemoreceptors
6
7
Ventilation Questions
1. Describe how ventilation regulates
blood pH.
2. Explain why the ventilatory threshold
is related to the lactate threshold
3. Can RER ever exceed 1.0? Under
what circumstances? Explain.
Young cowboys in
the old west
Matching O2 delivery
to muscle O2 needs
Regulation of cardiorespiratory system
Vascular system
aorta  arteries  arterioles 
capillaries 
venules  veins  vena cava
Vascular smooth muscle
allows vessels to
constrict in response to
SNS stimulation or local
factors
Arterioles and
Capillaries
 arterioles  terminal arterioles (TA)  capillaries 
collecting venules (CV) 
 arterioles regulate circulation into tissues
– under sympathetic and local control
 precapillary sphincters fine tune circulation within tissue
– under local control
Blood vessels are surrounded by
sympathetic nerves. A feed
artery was stained to reveal
catecholamine-containing nerve
fibers in vascular smooth muscle
cell layer. This rich network
extends throughout arterioles but
not into capillaries or venules.
Local factors that control arterioles
• PO2
• PCO2
• pH
• adenosine
• K+
• Nitric oxide
(1-adrenergic
receptor blocker)
30 s
Rapid adaptation of blood flow
Onset of exercise
Precapillary
sphincters fine-tune
local blood flow
Local control factors
• PO2
• PCO2
• pH
• adenosine
• K+
• temperature
Blood
Distribution
During Rest
Blood Flow Redistribution During
Exercise
At rest, most blood is found in the ______
while at exercise most blood is in _____.
A.
B.
C.
D.
E.
venous system; active muscle
pulmonary circulation; heart
arterioles; capillaries
heart; heart
liver; active muscle
What is the primary mechanism to
increase blood flow to working muscle?
A.
B.
C.
D.
E.
baroreceptors
sympathetic innervation
local factors
epinephrine
central command
What effect would these local conditions (from
resting values) have on arteriole blood flow?
PO2, PCO2, pH, temperature
A.
B.
C.
D.
increase flow
decrease flow
no effect on flow
cannot be determined
O2 Extraction
Moving O2 from blood into muscle
Factors affecting Oxygen Extraction
Fick equation
VO2 = Q  (aO2 – vO2)
O2 extraction
response to
exercise
Represents mixed
venous blood returning
to right heart
a-v O2 difference
 Bohr Effect: effect of local environment on
oxy-hemoglobin binding strength
 amount of O2 released to muscle depends on
local environment
– PO2, pH, PCO2, temperature, 2,3 DPG
 2,3 diphosphoglycerate (DPG)
– produced in RBC during prolonged, heavy
exercise
– binds loosely with Hb to reduce its affinity for O2
which increases O2 release
Bohr effect on
oxyhemoglobin
dissociation
Oxyhemoglobin
binding strength
affected by:
PO2
PCO2
H+
temperature
2,3 DPG
O2 unloading in muscle
O2 loading in lungs
A change in the local metabolic environment
has occurred: pH and PO2 have ; temperature
and PCO2 have .
What effect will these changes have on the
amount of O2 released to the muscle?
A.
B.
C.
D.
increase O2 release
decrease O2 release
no change in O2 release
cannot be determined
A change in the local metabolic environment
has occurred: pH and PO2 have ; temperature
and PCO2 have .
What do these changes in local environmental
suggest has occurred?
A. the muscles changed from an exercise to a
resting state
B. the muscles began to exercise
C. no change
D. cannot be determined
During graded exercise,
A. VCO2 increases linearly
B. A breakpoint occurs in VCO2 that
coincides with lactate threshold
C. A breakpoint occurs in VE that is
caused by increased VO2
D. A breakpoint occurs in VCO2 that
results from increased epinephrine
release
Which of the following would NOT cause
local vasodilation?
A.
B.
C.
D.
E.
 PCO2
 PO2
 temperature
 pH
 nitric oxide production
Which of the following would NOT cause
greater O2 unloading from hemoglobin?
A.
B.
C.
D.
E.
 PCO2
 PO2
 temperature
 pH
 nitric oxide production
Which of the following adaptations likely had the
LEAST influence for explaining why VO2max
increased 12% after completing a cross country
season?
A.  cardiac output
B.  blood volume
C.  mitochondrial volume
D.  capillary density
E.  number of RBC
Which of the following does NOT occur
during exercise?
A. Vasodilation occurs throughout body.
B. Blood is redirected towards exercising
muscle.
C. Local factors loosen binding of O2 to
hemoglobin.
D. Increased venous return causes
increased stroke volume.
E. There is increased afterload to heart.
Which of the following does NOT occur
during moderate-intensity running exercise?
A. Sympathetic stimulation increases blood
flow to working muscles.
B. PCO2 causes greater unloading of O2 to
working muscles from hemoglobin.
C. Sensory inputs from muscle afferent nerves
stimulate ventilation and heart rate.
D. PO2 in alveoli drops to less than the PO2 in
blood returning to the lungs.
E. There is little change to diastolic BP.
Control of cardiac function and
ventilation
Parallel activations
What would be the effect of local arteriole
dilation on BP?
A. Decrease BP
B. Increase BP
C. No effect on BP
During running exercise, total peripheral
resistance ____ because of _____.
A.
B.
C.
D.
increases; sympathetic stimulation
increases; local control factors
decreases; vasoconstriction
decreases; local control factors
Reflex control of cardiac output
Primary regulators
 Central command control center (medulla)
– Input from motor cortex
• parasympathetic inhibition predominates at HR <~100 bpm
• sympathetic stimulation predominates at HR >~100 bpm
– Sensory input from skeletal muscle afferent
• sense mechanical and metabolic environment
Secondary regulator
 arterial baroreceptors
– Provide input to central command
– located in carotid bodies and aortic arch
– respond to arterial pressure
• Reset during exercise
Maintaining Blood Pressure
Pressure is Necessary for Blood Flow
Pressure is
necessary for
blood to flow.
Notice that blood
flow decreases
with BP
Regulation of Blood Flow and
Pressure
Blood flow and pressure determined by:
A. Vessel resistance
(e.g. diameter) to
blood flow
B. Pressure difference
between two ends
A
cardiac
output
A
B
BP = Q  TPR
arterioles
B
Regulation of Blood Flow and
Pressure
120
Pressure
(mm Hg)
80
Time
BP = Q  TPR
At what level
is peripheral
resistance
greatest?
Effects of Exercise on Cardiac Output
Effects of Exercise Intensity on TPR
25
TPR
20
15
10
5
0
0
50
100
150
200
250
300
Treadmill speed (m/min)
350
400
Effects of Incremental Exercise on BP
250
Blood pressure (mm Hg)
225
200
175
150
125
100
75
Systolic BP
Diastolic BP
50
25
0
0
50
100
150
200
Workload (W)
250
300
Cardiovascular Response to Exercise
Fick equation
VO2 = Q  (aO2 – vO2)
VO2 = [HR  SV]  (aO2 – vO2)
VO2 = [BP  TPR]  (aO2 – vO2)
Exercise effects on heart
  HR caused by
–  sympathetic innervation
–  parasympathetic innervation
–  release of catecholamines
  SV, caused by
–  sympathetic innervation
–  venous return
  cardiac output
Cardiorespiratory adaptations
to endurance training
How does endurance training affect
VO2max?
Maximal oxygen consumption (VO2max)
VO2max
– highest VO2 attainable
– maximal rate at which aerobic system
utilizes O2 and synthesizes ATP
– single best assessment of CV fitness
VO2max
VO2
intensity
 VO2max affected by:
– genetics (responders vs. nonresponders)
– age
– gender
– specificity of training
Cardiorespiratory training adaptations
VO2max  ~15% with training
 ventilation?
– training has no effect on ventilation capacity
 O2 delivery?
– CO ( ~15%)
–  plasma volume
–  SV
 O2 utilization?
– mitochondrial volume  >100%
1995 marathon training data (women)
VO2
5 mph
6 mph
RER
5 mph
6 mph
HR
5 mph
6 mph
VO2max
HRmax
Pre-training
30.7
35.5
Post-training
29.8
34.6
0.92
0.95
0.88*
0.92*
168
182
54.4
206
151*
167*
58.5*
198*
*P < 0.05
Heart adaptations to training
 sympathetic
sensitivity
 heart size,
blood volume
Heart adaptations to training
Left ventricular adaptations depend
on training type
myocardial
thickness
LV-EDV
Endurance
trained
 preload
(volume overload)
Sedentary
Resistance
trained
 afterload
(pressure overload)
Normalized data for VO2max (mlkg-1min-1)
Category
%ile
Excellent
>80
Average
Age
20-29
>44
Age
40-49
>39
Age
60+
>33
40-60 36-39
31-35
25-28
Poor
<20
<31
<28
<22
Excellent
>80
>52
>49
>41
39-44
33-36
<28
<22
Average
Poor
40-60 43-47
<20
<31
Aerobic Center Longitudinal Study, 1970-2002
Women
Men
Which of the following would likely result in an
increase of VO2max?
A. breathing faster and deeper during
maximal exercise
B. faster HR at maximal exercise
C. ability to deliver more O2 to muscles
during maximal exercise
D. more mitochondria
Which of the following does NOT occur
following endurance training?
A.
B.
C.
D.
E.
F.
 blood volume
 HRmax
 SVmax
 COmax
 mitochondrial volume
 maximal ventilatory capacity
How would you evaluate a VO2max of 28.9
mL/kg/min for a 22-year-old man?
A.
B.
C.
D.
E.
excellent
above average
average
very low
dead
Which of the following exercises would
likely decrease TPR the LEAST?
A.
B.
C.
D.
E.
jogging
fast walking
shoveling snow
cycling
the above would decrease TPR
similarly
What is the mechanism for the sudden increase
in VE when the lactate threshold is reached
during an incremental exercise test?
A. greater muscle afferent input
B. greater stimulation of peripheral
baroreceptors
C. greater stimulation of peripheral PCO2
chemoreceptors
D. greater stimulation of peripheral PO2
chemoreceptors
E. greater stimulation from motor cortex