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. SaO2 would remain unchanged

b. SaO2 would be decreased

c. SaO2 would be increased

What effect might a decreased SaO2 have on O2 utilization by mitochondria?

a. no effect on mitochondrial VO2

b. will decrease mitochondrial VO2

c. will increase mitochondrial VO2

Pulmonary circulation

Pulmonary circulation varies with cardiac output

RBC

Single alveoli at rest showing individual RBCs

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 oxy-hemoglobin)

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.

CO2 + H2O H2CO3 H+ + HCO3-

Transport of O2 and CO2 in blood

Predict the relative O2 pressure differences between alveoli (PAO2) and arterial blood (PaO2)

a. PAO2 > PaO2

b. PAO2 = PaO2

c. 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 Lmin-1

– exercise: SV = 130 ml; HR = 180 bpm; Q = 23.4 Lmin-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 HeartSV dependent on venous return

muscle pump one-way venous valves breathing

Return of blood to heart

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. increased

b. decreased

c. no effect

d. 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

Onset of exercise

(1-adrenergic receptor blocker)

30 s

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. baroreceptors

b. sympathetic innervation

c. local factors

d. epinephrine

At rest, most blood is found in the ______ while at exercise most blood is in _____.

a. venous system; active muscle

b. pulmonary circulation; heart

c. arterioles; capillaries

d. heart; heart

e. 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

O2 loading in lungsO2 unloading in muscle

Oxyhemoglobin binding strength

affected by:PO2

PCO2

H+

temperature2,3 DPG

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. increase O2 release

b. decrease O2 release

c. no change in O2 release

d. 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 exercisec. no changed. 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

VO2 vs Power

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Power (W)

VO

2 (

L/m

in)

Ventilatory responses to incremental exercise

1. What was the subject doing? What data support your response?

2. What is the relationship of VO2 and exercise intensity?

VE vs VO2

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VO2 (L/min)

VE

(L/m

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VCO2 vs VO2

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Ventilatory responses to incremental exercise

Why is there a breakpoint in the linearity of VE and VCO2?

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

7.05

7.10

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7.35

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7.45

4 5 6 7 8 9 10 11 12 13 14 15

Treadmill Speed (mph)

pH

Respiratory Exchange Ratio

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Treadmill Speed (mph)

RE

R

RER = VCO2

VO2

Minute Ventilation

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CO2 Production

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VC

O2

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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. very light

b. moderate

c. hard

d. cannot be determined

What is the cause of hyperventilation during incremental exercise?

a. muscles cannot get enough O2

b. sympathetic innervationc. accumulation of lactate ions in bloodd. accumulation of H+ ions in blood

e. stimulation of PO2 chemoreceptors

VE vs VO2

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VO2 (L/min)

VE

(L/m

in)

VCO2 vs VO2

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VO2 (L/min)

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(L/m

in)

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

Time

120

Pressure(mm Hg)

80

blood pressure (BP) = cardiac output (Q) total peripheral resistance (TPR)

Regulation of Blood Flow and Pressure

Blood flow and pressure determined by:

arterioles

B. Pressure difference between two ends

A. Vessel resistance (e.g. diameter) to blood flow

A

A BB

cardiac output

Peripheral blood pressure

Where is the greatest resistance to blood flow?

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Treadmill speed (m/min)

TP

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Effects of exercise intensity on TPR

Effects of incremental exercise on BP

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Effects of isometric exercise on BP

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Time (s)

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Comparison of BP Response Between Arm

and Leg Ergometry

Why is the BP response to resistance exercise greater than cycling exercise?

a. greater HR response during cycling

b. greater decrease in TPR during resistance exercise

c. greater decrease in TPR during cycling exercise

d. 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

intensity

VO2VO2max

1995 marathon training data (women)

VO2 Pre-training Post-training 5 mph 30.7 29.8 6 mph 35.5 34.6

RER 5 mph 0.92 0.88* 6 mph 0.95 0.92*

HR 5 mph 168 151* 6 mph 182 167*

VO2max 54.4 58.5* HRmax 206 198*

*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 (mlkg-1min-1)

Category %ile Age 20-29

Age 40-49

Age 60+

Excellent >80 >44 >39 >33

Average 40-60 36-39 31-35 25-28

Poor <20 <31 <28 <22

Excellent >80 >52 >49 >41

Average 40-60 43-47 39-44 33-36

Poor <20 <31 <28 <22

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. definitely yes

b. definitely no

c. maybe

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?

. 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. excellent

b. above average

c. average

d. very low

e. dead

Which of the following adaptations likely had the LEAST influence for explaining why VO2max increased 12% after completing a cross country season?

. cardiac output

b. blood volume

c. mitochondrial volume

d. capillary density

e. number of RBC

Which of the following exercises would likely decrease TPR the LEAST?

a. jogging

b. fast walking

c. shoveling snow

d. cycling

e. 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?

. muscle afferent activation

b. H+ in blood

c. stimulation of motor cortex

d. PO2 in blood

e. PCO2 in blood

What is the primary mechanism for increasing VE at the onset of exercise?

. PO2 in blood

b. PCO2 in blood

c. blood pH

d. neural factors

e. all of the above are equally responsible