Cardiovascular and Respiratory Systems: Oxygen Transport Integration of Ventilation, Cardiac, and Circulatory Functions

Cardiorespiratory System Functions of cardiorespiratory system:  transportation of O 2 and CO 2  transportation of nutrients/waste products  distribution of hormones  thermoregulation  maintenance of blood pressure

Ability of cardiorespiratory system on maintaining arterial PO 2 (PaO 2 ) during graded exercise to exhaustion

Critical elements of O 2 Transport Pathway  Lungs  Ventilation –V E = RR  V T  O 2 diffusion into blood –PO 2 gradient determines O 2 movement –Hb  Heart and circulation –Q = HR  SV –cardiac output = muscle blood flow  O 2 diffusion into mitochondria –oxyhemoglobin dissociation relationship –Fick principle [VO 2 = Q  (CaO 2 – CvO 2 )]  Control of cardiorespiratory system –central control –peripheral inputs –maintenance of blood pH

Ventilation and Diffusion Getting O 2 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 m 2  at rest, RBCs remain in pulmonary capillaries for 0.75 s (capillary transit time) –transit time = s at maximal exercise adequate time to release CO 2 marginal time to take up O 2

PO 2 and PCO 2 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 O 2 (SaO 2 ) when pulmonary blood flow is faster than RBC can uptake O 2 ? a.SaO 2 would remain unchanged b.SaO 2 would be decreased c.SaO 2 would be increased

What effect might a decreased SaO 2 have on O 2 utilization by mitochondria? a.no effect on mitochondrial VO 2 b.will decrease mitochondrial VO 2 c.will increase mitochondrial VO 2

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 O 2 transported bound to hemoglobin  1-2% of O 2 is dissolved in blood

Hemoglobin  consists of four O 2 -binding heme (iron containing) molecules  combines reversibly w/ O 2 (forms oxy- hemoglobin)

Rate of gas diffusion is dependent upon pressure (concentration) gradient. Erythrocyte (RBC) ~98% of O 2 is bound up with hemoglobin (Hb) and transported from lungs to working muscle.

CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 - Transport of O 2 and CO 2 in blood

Predict the relative O 2 pressure differences between alveoli (P A O 2 ) and arterial blood (P a O 2 ) a.P A O 2 > P a O 2 b.P A O 2 = P a O 2 c.P A O 2 < P a O 2

Role of the Heart Moving O 2 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 –  Ca 2+ 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  P aO 2 –not normally involved in control  P aCO 2 –central P a CO 2 chemoreceptors are 1º control factor at rest H+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  muscle pump  one-way venous valves  breathing Return of blood to heart

Vascular system aorta  arteries  arterioles  capillaries  venules  veins  vena cava

Cardiovascular Response to Exercise Fick equation VO 2 = Q   (aO 2 – vO 2 ) VO 2 = [HR  SV]   (aO 2 – vO 2 ) VO 2 = [BP  TPR]   (aO 2 – vO 2 )

VO 2 = Q   (aO 2 – vO 2 ) How would VO 2 be affected if cardiac output/O 2 extraction were increased? a.increased b.decreased c.no effect d.cannot be determined

Matching O 2 delivery to muscle O 2 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.

Matching of Ventilation and Perfusion  100% of cardiac output flows through lungs –low resistance to flow  upper alveoli not opened during rest

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 VO 2 –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

Mechanisms of Blood Flow Redistribution  neural-hormonal control of arterioles –catecholamines –sympathetic control does NOT regulate capillaries  local control of arterioles and precapillary sphincters –P O 2, P CO 2, pH, K +, adenosine, temperature –nitric oxide (NO)

Inside of arterioles are endothelial cells that release nitric oxide (NO) in response to sheer stress, which causes vasodilation

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,  P O 2,  P CO 2,  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

O 2 Extraction Moving O 2 from blood into muscle

Factors affecting Oxygen Extraction Fick equation VO 2 = Q   (aO 2 – vO 2 )

O 2 extraction response to exercise Represents mixed venous blood

a-v O 2 difference  Bohr Effect: effect of local environment on oxy-hemoglobin binding strength  amount of O 2 released to muscle depends on local environment –PO 2, pH, PCO 2, temperature, 2,3 DPG  2,3 diphosphoglycerate (DPG) –produced in RBC during prolonged, heavy exercise –binds loosely with Hb to reduce its affinity for O 2 which increases O 2 release

Bohr effect on oxyhemoglobin dissociation O 2 loading in lungs O 2 unloading in muscle Oxyhemoglobin binding strength affected by: PO 2 PCO 2 H + temperature 2,3 DPG

A change in the local metabolic environment has occurred: pH and PO 2 have  ; temperature and PCO 2 have . What effect will these changes have on the amount of O 2 released to the muscle? a.increase O 2 release b.decrease O 2 release c.no change in O 2 release d.cannot be determined

A change in the local metabolic environment has occurred: pH and PO 2 have  ; temperature and PCO 2 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%) CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 -

Ventilatory Control of Blood pH

Ventilatory responses to incremental exercise 1.What was the subject doing? What data support your response? 2.What is the relationship of VO 2 and exercise intensity?

Ventilatory responses to incremental exercise Why is there a breakpoint in the linearity of VE and VCO 2 ?

Ventilatory Regulation of Acid-Base Balance CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 -  at low-intensity exercise, source of CO 2 is entirely from substrate metabolism  at high-intensity exercise, bicarbonate ions also contribute to CO 2 production –source of CO 2 is from substrates and bicarbonate ions (HCO 3 - ),   blood H + stimulates VE to rid excess CO 2 (and H + ) Can RER ever exceed 1.0? When? Explain

RER = VCO 2 VO 2

Ventilatory threshold: breakpoint in VE linearity— corresponds to lactate threshold

A subject completed a treadmill test in which the end-exercise RER was 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 O 2 b.sympathetic innervation c.accumulation of lactate ions in blood d.accumulation of H + ions in blood e.stimulation of PO 2 chemoreceptors

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 B B cardiac output

Peripheral blood pressure Where is the greatest resistance to blood flow?

Effects of exercise intensity on TPR

Effects of incremental exercise on BP

Effects of isometric exercise on BP

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 VO 2max ?

Maximal oxygen consumption (VO 2max ) VO 2max –highest VO 2 attainable –maximal rate at which aerobic system utilizes O 2 and synthesizes ATP –single best assessment of CV fitness intensity VO 2 VO 2max

1995 marathon training data (women)

Heart adaptations to training

Myocardial adaptations to training Endurance trained Sedentary Resistance trained

Cardiorespiratory training adaptations VO 2max  ~15% with training  ventilation? –training has no effect on ventilation capacity  O 2 delivery? –CO (  ~15%) –  plasma volume –  SV  O 2 utilization? –mitochondrial volume  >100%

 VO 2max affected by: –genetics (responders vs. nonresponders) –age –gender –specificity of training

Normalized data for VO 2max (ml  kg -1  min -1 ) Women Men

As the SDSU women’s cross-country coach, would you be interested in a recruit who has a VO 2max 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 VO 2max ? 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.  blood volume b.  HR max c.  SV max d.  CO max e.  mitochondrial volume f.  maximal ventilatory capacity

Quiz 5 1.  fat use;  RER 2.  ß-oxidation enzymes 3.endurance;  mitochondrial enzymes 4.shifted LT to right;  ß- oxidation enzymes 5.d 6.a 7.c 8.a 9.  PO 2,  PCO 2,  pH,  temp,  NO release 10.d 11.b 12.  BP w/ weight lifting; slow contracting muscle occludes blood flow; TPR doesn’t  as much as during running 13.d 14.d 15.a 16.d 17.a, c 18.a)  ; b)  ; c)  ; d)  ; e)  ; f)  ; g) 

How would you evaluate a VO 2max 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 VO 2max 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 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? a.  muscle afferent activation b.  H + in blood c.  stimulation of motor cortex d.  PO 2 in blood e.  PCO 2 in blood

What is the primary mechanism for increasing VE at the onset of exercise? a.  PO 2 in blood b.  PCO 2 in blood c.  blood pH d.neural factors e.all of the above are equally responsible