Oxygen Transport Systems

Integration of Ventilation, Cardiac, and Circulatory Functions

Cardiovascular Function

transportation of O2 and CO2

transportation of nutrients/waste products distribution of hormones thermoregulation maintenance of blood pressure

Long Refractory Period in Cardiac Muscle Prevents Tetany

Cardiac Fibers Develop Graded Tension

Frank-Starling Law of the Heart

graded Ca2+ release from SR– dependent on

Ca2+ influx through DHP channels

Autorhythmic cells depolarize spontaneously– leaky

membrane– SA and AV

node

Central command input and output

Group III

Cardiac output affected by:

1. preload – end diastolic pressure (amount of myocardial stretch)

affected by venous return

2. afterload – resistance blood encounters as it leaves ventricles

affected by arterial BP

3. contractility – strength of cardiac contraction

4. heart rate

Mechanisms affecting HRVO2 = HR SV (a-v O2)

Sinoatrial node is pacemaker for heart– spontaneously depolarizes

• leakiness to Na+

– influenced by autonomic NS• training down-regulates ß-adrenergic system

causing bradycardia

Cardiac Output Regulation

Extrinsic control autonomic nervous

system– sympathetic NS (1

control at HR >100 bpm)– parasympathetic NS (1

control at HR <100 bpm)– stimulates ß-adrenergic

receptors on myocardium hormonal

– EPI, NE

Mechanisms affecting SV VO2 = [HR SV] (a-v O2)

amount of Ca2+ influx– APs open Ca2+ channels on t-

tubules– also stimulates Ca2+ release

from SR length-tension relationship

– [Ca2+]-tension relationship

ß1-adrenergic modulation– activates cAMP

phosphorylates L-type Ca2+, SR Ca2+ channels and pumps, troponin

Ca2+ influx and Ca2+ release from SR

training LV EDV

Intrinsic control Frank-Starling

Principle Ca2+ influx w/

myocardial stretch– stretched fibers work

at optimal length-tension curve

Dotted lines indicate end-systole and end-diastole

Cardiovascular Response to Exercise

Laughlin, M.H. Cardiovascular responses to exercise. Adv. Physiol. Educ. 22(1): S244-S259, 1999. [available on-line]

Cardiovascular Response to Exercise

Fick principle

VO2 = Q (CaO2 – CvO2)

VO2 = [HR SV] (CaO2 – CvO2)

VO2 = [BP TPR] (CaO2 – CvO2)

Exercise Effects on Cardiac Output

HR caused by sympathetic innervation parasympathetic innervation release of catecholamines

SV, caused by sympathetic innervation venous return

Myocardial Mechanisms Influencing SV During Exercise

SV = EDV – ESV Factors that influence SV

– Heart size (LVV)– LV compliance during diastole

Progressive in ESV with graded exercise is from contractility– Attributed to sympathetic NS, length-tension

changes• Influx of Ca2+ through L-type Ca2+ channels stimulates

Ca2+ from SR release channels (Ca2+-induced Ca2+-release)

Role of Ca2+ in Cardiac Function

influx of Ca2+ through L-type Ca2+ channels stimulates Ca2+ from SR release channels (Ca2+-induced Ca2+-release)

amount of Ca2+ released from SR dependent on sarcomere length

SERCA pumps return Ca2+ to sarcoplasmic reticulum sympathetic -adrenergic stimulation contractile

force and relaxation time– affects Ca2+ sensitivity through phosphorylation– increases length of diastole to filling time

HR and Q responses to exercise intensity

SV during graded running

Zhou et al., MSSE, 2001

Effect of training and maximal exercise on VO2, Q, and a-v O2 difference

VO2 (L·min-1)

Q(L·min-1)

a-v O2

difference (ml O2·100 ml-1)

Untrained man

at rest 0.25 5.0 5.0

at maximal intensity 3.00 20.0 15.0

fold increase 12 4 3

Elite endurance male athlete

at rest 0.25 5.0 5.0

at maximal intensity 6.00 37.5 16.0

fold increase 24 7.5 3.2

Effect of training and maximal exercise on VO2, Q, and a-v O2 difference

VO2 (L·min-1)

HR(bpm)

SV(ml·beat-1)

a-v O2

difference (ml O2·100 ml-1)

Untrained individual

at rest 0.25 72 70 5.0

at maximal intensity 3.00 200 100 15.0

fold increase 12 2.8 0.7 3.0

Elite endurance athlete

at rest 0.25 40 125 5.0

at maximal intensity 6.00 195 192 16.0

fold increase 24 4.9 1.5 3.2

Effects of Exercise on Blood Pressure

BP = Q TPR

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

capillary density 1 determinant of O2 diffusion

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

0

5

10

15

20

25

0 50 100 150 200 250 300 350 400

Treadmill speed (m/min)

TP

R

Effects of Exercise Intensity on TPR

Effects of Incremental Exercise on BP

0

25

50

75

100

125

150

175

200

225

250

0 50 100 150 200 250 300

Workload (W)

Blo

od

pre

ssu

re (

mm

Hg

)

Systolic BP

Diastolic BP

Effects of Isometric Exercise on BP

0

25

50

75

100

125

150

175

200

225

0 30 60 90 120 150

Time (s)

Blo

od

pre

ssu

re (

mm

Hg

)

Systolic BP

Diastolic BP

Control of Blood Flow

Blood flow to working muscle increases linearly with muscle VO2

Blood Distribution During Rest

Blood Flow Redistribution During Exercise

Effect of exercising muscle mass on blood flow

Onset of exercise

(1-adrenergic receptor blocker)

30 s

Local Control of Microcirculation

metabolic factors that cause local vasodilation PO2

PCO2

H+

– adenosine endothelial factors that cause local vasodilation

– nitric oxide (NO)• released with shear stress and EPI• redistributed from Hb—greater O2 release from Hb induces

NO release as well

Adenosine metabolism in myocytes and endothelial cells

ATP ADP AMP adenosine

Adenosine is released in response to hypoxia, ischemia, or increased metabolic work

Single layer of endothelial cells line innermost portion of arterioles that releases nitric oxide (NO) causing

vasodilation

Hemoglobin

consists of four O2-binding heme (iron containing) molecules

combines reversible w/ O2 (oxy-hemoglobin)

Bohr Effect – O2 binding affected by

– PO2

– PCO2

– pH

– temperature

– 2,3-DPG (diphosphoglycerate)

CO2 transport

Factors affecting Oxygen Extraction

Fick principle

VO2 = Q (CaO2 – CvO2)

O2 extraction during graded exercise

Sympathetic stimulation causes spleen to constrict releasing RBC into blood,

thus increasing O2-carrying capacity

Bohr effect on oxyhemoglobin

dissociation

PO2, pH and PCO2, temperature,

and 2,3 DPG shift curve to left causing

greater O2 release

Cardiovascular Adaptations to Training

HR and Q responses to exercise intensity

SV during graded running

Zhou et al., MSSE, 2001

Cardiovascular Adaptations to Endurance Training

VO2max = HRmax SVmax (a-v O2 diff)max

~50% of VO2max is because of SVmax

1 mechanism is from LV-EDV compliance (ability to stretch) myocardial growth (longitudinal and cross-

sectional)• longitudinal growth doesn’t affect sarcomere length

contractility (systolic function) and relaxation (diastolic function) Ca2+ sensitivity Ca2+ removal

Left ventricular adaptations depend on training type

Endurance trained preload

(volume overload)

SedentaryResistance

trained afterload

(pressure overload)

LV-EDV myocardial thickness

Ventilation

PO2 and PCO2 in lungs and blood

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

– CO2 + H2O H2CO3 H+ + HCO3-

Matching of Ventilation and Perfusion

100% of cardiac output flows through lungs– low resistance to flow

pulmonary capillaries cover 70-80% of alveolar walls

upper alveoli not opened during rest

Pulmonary Gas Exchange

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)– 0.4-0.5 s at maximal exercise

• adequate to release CO2; marginal to take up O2

O2 and CO2 exchange in alveolar capillaries

PO2 = 40PCO2 = 46

Gas Exchange and Transport

Oxygen Transport ~98% of O2 transported bound to

hemoglobin

Carbon Dioxide Transport dissolved in plasma (~7%) bound to hemoglobin (~20%) as a bicarbonate ion (~75%)

CO2 + H2O H2CO3 H+ + HCO3-

Hemoglobin

consists of four O2-binding heme (iron containing) molecules

combines reversible w/ O2 (oxy-hemoglobin)

Bohr Effect – O2 binding affected by– temperature

– pH

– PO2

– PCO2

– 2,3-DPG (diphosphoglycerate)

Bohr effect on oxyhemoglobin

dissociation

CO2 transport

Ventilatory Control of Blood pH

Ventilatory Regulation of Acid-Base Balance

CO2 + H2O H2CO3 H+ + HCO3-

source of these expired carbons is from bicarbonate ions (HCO3

-), NOT substrates at low-intensity exercise, source of CO2 is

entirely from substrates at high-intensity exercise, bicarbonate ions

also contribute to VCO2

Can RER every exceed 1.0? When? Explain

Minute Ventilation

0.0

20.0

40.0

60.0

80.0

100.0

120.0

140.0

160.0

180.0

200.0

2 3 4 5 6 7 8 9 10 11 12 13 14 15

Treadmill Speed (mph)

Min

ute

Ven

tila

tio

n (

L/m

in)

VE and VO2 Response to

Incremental Exercise

Blood pH

7.05

7.10

7.15

7.20

7.25

7.30

7.35

7.40

7.45

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

Treadmill Speed (mph)

pH

CO2 Production

0

10

20

30

40

50

60

70

80

90

2 3 4 5 6 7 8 9 10 11 12 13 14 15

Treadmill Speed (mph)

VC

O2

(m

l/k

g/m

in)

Respiratory Exchange Ratio

0.8

0.9

1.0

1.1

1.2

1.3

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

Treadmill Speed (mph)

RE

R

Ventilatory equivalents for VO2 (dark blue) and VCO2 (yellow). Arrow indicates occurrence of ventilatory threshold.

15

20

25

30

35

100 125 150 175 200 225 250 275 300 325 350 375

Treadmill Speed (m/min)

VE

/VO

2