Cardiovascular and Respiratory
Systems: Oxygen Transport
Integration of Ventilation, Cardiac,
and Circulatory Functions
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 on maintaining
arterial PO2 (PaO2)
during graded exercise
to exhaustion
Critical elements of O2 Transport Pathway
 Lungs
 Ventilation
– VE = RR  VT
 O2 diffusion into blood
– PO2 gradient determines O2 movement
– Hb
 Heart and circulation
– Q = HR  SV
– cardiac output = muscle blood flow
 O2 diffusion into mitochondria
– oxyhemoglobin dissociation relationship
– Fick principle [VO2 = Q  (CaO2 – CvO2)]
 Control of cardiorespiratory system
– central control
– peripheral inputs
– maintenance of blood pH
Ventilation and Diffusion
Getting O2 from air into blood
A. Major
pulmonary
structure
B. General view
showing alveoli
C. Section of
lung showing
individual alveoli
D. Pulmonary
capillaries within
alveolar walls
Pulmonary Gas Exchange
 gases move because of pressure
(concentration) gradients
 alveolar thickness is ~ 0.1 µm
 total alveolar surface area is ~70 m2
 at rest, RBCs remain in pulmonary capillaries
for 0.75 s (capillary transit time)
– transit time = 0.4-0.5 s at maximal exercise
• adequate time to release CO2
• marginal time to take up O2
PO2 and PCO2 gradients in body
Pressure gradients for gas transfer at rest: Time required for
gas exchange in lungs (left) and tissue (right)
What would be the effect on the saturation of
arterial blood with O2 (SaO2) when
pulmonary blood flow is faster than RBC
can uptake O2?
a.
b.
c.
SaO2 would remain unchanged
SaO2 would be decreased
SaO2 would be increased
What effect might a decreased SaO2 have on
O2 utilization by mitochondria?
a.
b.
c.
no effect on mitochondrial VO2
will decrease mitochondrial VO2
will increase mitochondrial VO2
Pulmonary circulation
 Pulmonary circulation varies with
cardiac output
Single alveoli at rest
showing individual RBCs
RBC
Single alveoli under high flow
showing increased RBCs
Gas Exchange and Transport
Oxygen transport
 ~98% of O2 transported bound to
hemoglobin
 1-2% of O2 is dissolved in blood
Hemoglobin
 consists of four O2-binding heme (iron
containing) molecules
 combines reversibly w/ O2 (forms oxyhemoglobin)
Rate of gas diffusion is dependent
upon pressure (concentration)
gradient.
Erythrocyte (RBC) ~98% of O2 is
bound up with hemoglobin (Hb)
and transported from lungs to
working muscle.
Transport of O2 and CO2 in blood
CO2 + H2O  H2CO3  H+ + HCO3-
Predict the relative O2 pressure differences
between alveoli (PAO2) and arterial blood
(PaO2)
a.
b.
c.
PAO2 > PaO2
PAO2 = PaO2
PAO2 < PaO2
Role of the Heart
Moving O2 from lungs to working
muscle
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
Control of cardiac function and
ventilation
Parallel activations
Reflex control of cardiac output
Primary regulators
 cardiovascular control center (medulla)
– w/ activation of motor cortex, parallel activation of
sympathetic/parasympathetic nerves
• parasympathetic inhibition predominates at HR <~100 bpm
• sympathetic stimulation predominates at HR >~100 bpm
 skeletal muscle afferents
– sense mechanical and metabolic environment
Secondary regulator
 arterial baroreceptors
– located in carotid bodies and aortic arch
– respond to arterial pressure
• Reset during exercise
Cardiac Regulation
Intrinsic control
 Frank-Starling Principle
–  Ca2+ influx w/ myocardial stretch
Extrinsic control
 autonomic nervous system
– sympathetic NS (1 control at HR >100 bpm)
– parasympathetic NS (1 control at HR <100 bpm)
 peripheral input
– chemoreceptors, baroreceptors, muscle afferents
 hormonal
– EPI, NE (catecholamines)
Humoral Chemoreceptors
 PaO2
– not normally involved in control
 PaCO2
– central PaCO2 chemoreceptors are 1º control factor
at rest
 H+
– peripheral H+ chemoreceptors are important factor
during high-intensity exercise
Control of Ventilation
 Central command and muscle afferents
are primary control mechanisms
 H+ chemoreceptors responsible for
“fine-tuning” ventilation
Describe the mechanisms that control
cardiac output and ventilation.
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
Venus Blood Return to Heart
SV dependent on venous return
Return of blood to heart
 muscle pump
 one-way venous valves
 breathing
Cardiovascular Response to Exercise
Fick equation
VO2 = Q  (aO2 – vO2)
VO2 = [HR  SV]  (aO2 – vO2)
VO2 = [BP  TPR]  (aO2 – vO2)
VO2 = Q  (aO2 – vO2)
How would VO2 be affected if cardiac output/O2
extraction were increased?
a.
b.
c.
d.
increased
decreased
no effect
cannot be determined
Matching O2 delivery
to muscle O2 needs
Regulation of cardiorespiratory system
Effects of Exercise on Cardiac Output
HR and SV responses to exercise intensity
Exercise effects on heart
  HR caused by
–  sympathetic innervation
–  parasympathetic innervation
–  release of catecholamines
  SV, caused by
–  sympathetic innervation
–  venous return
  cardiac output
Increasing Blood Flow to Working
Muscle During Exercise
Blood flow redistribution
Blood
Distribution
During Rest
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 blood flow control
 general sympathetic response occurs with
exercise onset that causes vasoconstriction
 exercise hyperemia = increase in blood flow
to cardiac and skeletal muscle
 blood flow to working muscle increases
linearly with muscle VO2
– muscle metabolic rate is key in controlling muscle
blood flow
– controlled primarily by local factors
(1-adrenergic
receptor blocker)
30 s
Onset of exercise
Blood Flow Redistribution During
Exercise
Capillaries
 flow of blood
– aorta  arteries  arterioles  capillaries 
venules  veins  vena cava
 arterioles regulate blood flow into muscle
– under sympathetic and local control
 precapillary sphincters fine tune blood flow
within muscle
– under only local control
• adenosine, PO2, PCO2, pH, nitric oxide (NO)
What is the primary mechanism to increase
blood flow to working muscle?
a.
b.
c.
d.
baroreceptors
sympathetic innervation
local factors
epinephrine
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
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
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
Carbon dioxide transport
 dissolved in plasma (~7%)
 bound to hemoglobin (~20%)
 as a bicarbonate ion (~75%)
CO2 + H2O  H2CO3  H+ + HCO3-
Ventilatory Control of Blood pH
Ventilatory responses to incremental
exercise
VO2 vs Power
1. What was the
subject doing?
What data support
your response?
7.00
6.00
VO2 (L/min)
5.00
4.00
2. What is the
relationship of VO2
and exercise
intensity?
3.00
2.00
1.00
0.00
0
100
200
300
Power (W)
400
500
Ventilatory responses to incremental
exercise
VCO2 vs VO2
200
5
180
4.5
160
4
140
3.5
VCO2 (L/min)
VE (L/min)
VE vs VO2
120
100
80
3
2.5
2
60
1.5
40
1
20
0.5
0
0
0
1
2
3
4
VO2 (L/min)
5
6
7
0
1
2
3
4
5
VO2 (L/min)
Why is there a breakpoint in the linearity of VE and VCO2?
6
Ventilatory Regulation of Acid-Base
Balance
CO2 + H2O  H2CO3  H+ + HCO3-
 at low-intensity exercise, source of CO2 is
entirely from substrate metabolism
 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
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
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)
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)
Ventilatory
threshold:
breakpoint in VE
linearity—
corresponds to
lactate threshold
A subject completed a treadmill test in which the
end-exercise RER was 0.98. Predict the
subject’s RPE.
a.
b.
c.
d.
very light
moderate
hard
cannot be determined
VCO2 vs VO2
200
5
180
4.5
160
4
140
3.5
VCO2 (L/min)
VE (L/min)
VE vs VO2
120
100
80
3
2.5
2
60
1.5
40
1
20
0.5
0
0
0
1
2
3
4
5
6
7
0
1
VO2 (L/min)
2
3
4
VO2 (L/min)
What is the cause of hyperventilation during
incremental exercise?
a.
b.
c.
d.
e.
muscles cannot get enough O2
sympathetic innervation
accumulation of lactate ions in blood
accumulation of H+ ions in blood
stimulation of PO2 chemoreceptors
5
6
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.
Effects of Exercise on Blood Pressure
BP = Q  TPR
Regulation of Blood Flow and
Pressure
120
Pressure
(mm Hg)
80
Time
blood pressure (BP) = cardiac output (Q) 
total peripheral resistance (TPR)
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
arterioles
B
Peripheral blood pressure
Where is the greatest resistance to blood flow?
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
Effects of isometric exercise on BP
Blood pressure (mm Hg)
225
200
175
150
125
100
75
Systolic BP
Diastolic BP
50
25
0
0
30
60
90
Time (s)
120
150
Comparison of
BP Response
Between Arm
and Leg
Ergometry
Why is the BP response to resistance exercise
greater than cycling exercise?
a.
b.
c.
d.
greater HR response during cycling
greater decrease in TPR during resistance exercise
greater decrease in TPR during cycling exercise
cardiac output is less during resistance exercise
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
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
Heart adaptations to training
Myocardial adaptations to training
Endurance
trained
Sedentary
Resistance
trained
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%
 VO2max affected by:
– genetics (responders vs. nonresponders)
– age
– gender
– specificity of training
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
As the SDSU women’s cross-country coach,
would you be interested in a recruit who has
a VO2max of 29.8 ml/kg/min?
a.
b.
c.
definitely yes
definitely no
maybe
Which of the following would likely result in an
increase of VO2max?
a.
b.
c.
d.
breathing faster and deeper during maximal
exercise
faster HR at maximal exercise
ability to deliver more O2 to muscles during
maximal exercise
more mitochondria
Which of the following does NOT occur
following endurance training?
a.  blood volume
b.  HRmax
c.  SVmax
d.  COmax
e.  mitochondrial volume
f.  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 adaptations likely had the
LEAST influence for explaining why VO2max
increased 12% after completing a cross
country season?
a.  cardiac output
b.
c.
d.
e.
 blood volume
 mitochondrial volume
 capillary density
 number of RBC
Which of the following exercises would likely
decrease TPR the LEAST?
a.
b.
c.
d.
e.
jogging
fast walking
shoveling snow
cycling
all the above would decrease TPR similarly
What is the cause of the sudden increase in VE
when the lactate threshold is reached during
an incremental exercise test?
a.
b.
c.
d.
e.
 muscle afferent activation
 H+ in blood
 stimulation of motor cortex
 PO2 in blood
 PCO2 in blood
What is the primary mechanism for increasing
VE at the onset of exercise?
a.
b.
c.
d.
 PO2 in blood
 PCO2 in blood
 blood pH
neural factors
e.
all of the above are equally responsible