Oxygen Transport Systems Integration of Ventilation, Cardiac, and Circulatory Functions

Cardiovascular Function  transportation of O 2 and CO 2  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 Ca 2+ release from SR –dependent on Ca 2+ 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 HR VO 2 = HR  SV   (a-v O 2 ) 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 VO 2 = [HR  SV]   (a-v O 2 )  amount of Ca 2+ influx –APs open Ca 2+ channels on t- tubules –also stimulates Ca 2+ release from SR  length-tension relationship –[Ca 2+]- tension relationship  ß 1 -adrenergic modulation –activates cAMP  phosphorylates L-type Ca 2+, SR Ca 2+ channels and pumps, troponin –  Ca 2+ influx and Ca 2+ release from SR  training  LV EDV

Intrinsic control  Frank-Starling Principle –  Ca 2+ 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, [available on-line]available on-line

Cardiovascular Response to Exercise Fick principle VO 2 = Q  (Ca O 2 – Cv O 2 ) VO 2 = [HR  SV]  (Ca O 2 – Cv O 2 ) VO 2 = [BP  TPR]  (Ca O 2 – Cv O 2 )

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 Ca 2+ through L-type Ca 2+ channels stimulates Ca 2+ from SR release channels (Ca 2+ -induced Ca 2+ - release)

Role of Ca 2+ in Cardiac Function  influx of Ca 2+ through L-type Ca 2+ channels stimulates Ca 2+ from SR release channels (Ca 2+ - induced Ca 2+ -release)  amount of Ca 2+ released from SR dependent on sarcomere length  SERCA pumps return Ca 2+ to sarcoplasmic reticulum  sympathetic  -adrenergic stimulation  contractile force and relaxation time –affects Ca 2+ 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 VO 2, Q, and a-v O 2 difference VO 2 (L·min -1 ) Q (L·min -1 ) a-v O 2 difference (ml O 2 ·100 ml -1 ) Untrained man at rest at maximal intensity fold increase1243 Elite endurance male athlete at rest at maximal intensity fold increase

Effect of training and maximal exercise on VO 2, Q, and a-v O 2 difference VO 2 (L·min -1 ) HR (bpm) SV (ml·beat -1 ) a-v O 2 difference (ml O 2 ·100 ml -1 ) Untrained individual at rest at maximal intensity fold increase Elite endurance athlete at rest at maximal intensity fold increase

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 O 2 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 B B cardiac output

Effects of Exercise Intensity on TPR

Effects of Incremental Exercise on BP

Effects of Isometric Exercise on BP

Control of Blood Flow Blood flow to working muscle increases linearly with muscle VO 2

Blood Distribution During Rest

Blood Flow Redistribution During Exercise

Effect of exercising muscle mass on blood flow

Mechanisms of Blood Flow Redistribution  neural-hormonal control –catecholamines –sympathetic control  local control –P O 2, P CO 2, pH, K +, adenosine, temperature –nitric oxide (NO) affects skeletal muscle, myocardium, skin blood flow

Onset of exercise (  1 -adrenergic receptor blocker) 30 s

Local Control of Microcirculation  metabolic factors that cause local vasodilation –PO2–PO2 –  P CO 2 –H+–H+ –adenosine  endothelial factors that cause local vasodilation –nitric oxide (NO) released with  shear stress and EPI redistributed from Hb—greater O 2 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 O 2 -binding heme (iron containing) molecules  combines reversible w/ O 2 (oxy-hemoglobin)  Bohr Effect – O 2 binding affected by –PO2–PO2 –P CO 2 –pH –temperature –2,3-DPG (diphosphoglycerate)

CO 2 transport

Factors affecting Oxygen Extraction Fick principle VO 2 = Q  (Ca O 2 – Cv O 2 )

O 2 extraction during graded exercise Sympathetic stimulation causes spleen to constrict releasing RBC into blood, thus increasing O 2 -carrying capacity

Bohr effect on oxyhemoglobin dissociation  PO 2, pH and  PCO 2, temperature, and 2,3 DPG shift curve to left causing greater O 2 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 VO 2max = HR max  SV max  (a-v O 2 diff) max ~50% of  VO 2max is because of  SV max  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) –  Ca 2+ sensitivity –  Ca 2+ removal

Left ventricular adaptations depend on training type Endurance trained  preload (volume overload) Sedentary Resistance trained  afterload (pressure overload)  LV-EDV  myocardial thickness

Ventilation

P O 2 and P CO 2 in lungs and blood

Humoral Chemoreceptors  P A O2 –not normally involved in control  P A CO2 –central P A CO2 chemoreceptors are 1º control factor at rest H+H+ –peripheral H + chemoreceptors are important factor during high-intensity exercise –CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 -

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

O 2 and CO 2 exchange in alveolar capillaries PO 2 = 40 PCO 2 = 46

Gas Exchange and Transport Oxygen Transport  ~98% of O 2 transported bound to hemoglobin 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 -

Hemoglobin  consists of four O 2 -binding heme (iron containing) molecules  combines reversible w/ O 2 (oxy-hemoglobin)  Bohr Effect – O 2 binding affected by –temperature –pH –PO2–PO2 –P CO 2 –2,3-DPG (diphosphoglycerate)

Bohr effect on oxyhemoglobin dissociation

CO 2 transport

Ventilatory Control of Blood pH

Ventilatory Regulation of Acid- Base Balance CO 2 + H 2 O  H 2 CO 3  H + + HCO 3 -  source of these expired carbons is from bicarbonate ions (HCO 3 - ), NOT substrates  at low-intensity exercise, source of CO 2 is entirely from substrates  at high-intensity exercise, bicarbonate ions also contribute to VCO 2 Can RER every exceed 1.0? When? Explain

VE and VO 2 Response to Incremental Exercise

Ventilatory equivalents for VO 2 (dark blue) and VCO 2 (yellow). Arrow indicates occurrence of ventilatory threshold.