Integrated cardiovascular and respiratory reflexes Flashcards
what does the only energy system that can fuel prolonged muscular exercise require
oxygen
what is the challenge of exercise
controlling the CR system so that mitochondrial oxygen consumption and CO2 production can continue, homeostasis is maintained
what causes the challenge of exercise
at onset of exercise there is:
- rapid increase in oxygen consumption
- rapid increase in carbon dioxide production
the body ability to tolerate rapid changes in local PCO2 and PO2 is limited
- CR system must respond rapidly for contraction to continue and PCO2, PO2 homeostasis be maintained
VO2
rate of oxygen uptake by lungs
VCO2
rate of carbon dioxide output by lungs
VE
minute ventialtion
PaO2
partial pressure of arterial oxygen
PAO2
partial pressure of alveolar oxygen
PVO2
partial pressure of mixed venous oxygen
PVCO2
partial pressure of mixed venous carbon dioxide
VO2 at BMR compared to excersie
rest: 250ml/min
exercise: 3000ml/min
VE at BMR compared to exercise
rest: 5l/min
exercise: >150l/min
where do gas partial pressures change the most in exercise
skeletal muscle capillaries.
small changes in venous blood too
Partial pressures at BMR OXYGEN arterial blood skeletal muscle venous blood CARBON D arterial blood skeletal muscle venous blood
Partial pressures at BMR OXYGEN arterial blood- 100mmHg skeletal muscle 40mmHg venous blood 40mmHg CARBON D arterial blood 40mmHg skeletal muscle 46mmHg venous blood 46mmHg
Partial pressures during exercise OXYGEN arterial blood skeletal muscle venous blood CARBON D arterial blood skeletal muscle venous blood
Partial pressures during exercise OXYGEN arterial blood- 100mmHg skeletal muscle 0mmHg venous blood 0mmHg CARBON D arterial blood 30mmHg skeletal muscle 90mmHg venous blood 90mmHg
mmHg : kpA
7.5mmHg : 1 kPa
where does venous blood go
heart
where does arterial blood go
all tissues
what causes the drop in arterial PCO2 in exercise?
drops from 40 at rest to 30, despite raised PCO2 in skeletal muscle.
This is because acidosis causes more CO2 to be exhaled during exercise
how is oxygen carried in blood
- physically dissolved in plasma solution
- chemically bound to Hb
how much oxygen is dissolved in plasma
3ml/L of blood
which oxygen in blood accounts for PO2
only oxygen dissolved in plasma exerts partial pressure
what does PO2 play a role in
- regulation of breathing
- loading of Hb in lungs and release of O2 at tissues
how much oxygen is bound to Hb
197ml / L of blood
how does oxygen bind to Hb
Hb has 4 Fe2+ sites per Hb molecule, each bind to one O2 molecule
total oxygen in blood
200ml per litre of blod
3ml dissolved in plasma
197ml bound to Hb
CO2 carriage in blood
- physically dissolved in plasma
- bound to terminal amine groups of proteins in plasma and RBC
- as bicarbonate ions
what role does PCO2 play
chemical basis for control of breathing
which carbon dioxide in blood accounts for PCO2
only CO2 dissolved in plasma
what does CO2 bind to on RBC
alpha and beta chains in Hb
Role of bicarbonate ions in tissues
CO2 + H2O -> H2CO3 -> HCO3- + H+
H+ is buffered by RBC to maintain pH
Role of bicarbonate ions in lungs
H+ + HCO3- -> H2CO3 -> H2O + CO2
as CO2 leaves the blood, equilibrium is reversed
what is carbonic anhydrase and were is it found
reversibly catabolises conversion of CO2 and H2O to carbonic acid
found in RBC
where is majority of CO2 transported in blood
70% in RBC
30% in plasma
how is ventilation controlled
different negative feedback loops, based on sensors in the body
important sensors in body for controlling ventilation
Central and peripheral chemoreceptors
- detect changes in PO2, PCO2 and pH
- send signals back to respiratory control centres in brain stem
- reflex adjust ventilation to maintain blood gas homeostasis
where are respiratory control neurones
pons, medulla and other regions
what are effectors in ventilation control
respiratory muscles inspiration: - diaphragm - external intercostals expiration - internal intercostals -abdominal muscles
what are the sensors in ventilation control
central and peripheral chemoreceptors are the main ones. Others:
- lung and airway receptors
- joint and muscle receptors
- arterial baroreceptors
- pain and temperature
where are central chemoreceptors
just below viral surface of medusa, bathed in brain extracellular fluid
what stimulates central chemoreceptors
changes in pH when CO2 diffuses out of capilaries
- H+ cannot cross BBB but CO2 can
- CO2 reacts to form carbonic acid once passed BBB
- rapidly dissociates to form bicarbonate and H+ which are detected by chemoreceptors
what happens when central chemoreptors detect change in H+
signal to medullary respiratory neurones which controls adjustment of ventilation
how much of the ventilatory response are chemoreceptors responsible for
70%
where are peripheral chemoreceptors
in carotid bodies - not carotid sinus
what is the primary site for detecting arterlia hypoxia
peripheral chemoreceptors
what do peripheral chemoreceptors detect
- arterial hypoxia (low PaO2)
- sensitive to PC and pH, K+ and other substances like adrenaline
phases of ventilation response to constant load exercise
I) immediate increase at onset
II) exponential rise
III) steady state
- steady state will not be achieved above anaerobic threshold
when is steady state ventilation not achieved
in heavy exercise, above anaerobic threshold
what does ventilation increase proportionately to
metabolic rate
what can ventilation increase to
beyond 150L/minute
what does the relationship between ventilation and metabolic rate tell us
ventilation increases proportionally to metabolic rate, and can increase beyond 150L/min
THEREFORE
control mechanism that drives increase in breathing must be responsible for:
- immediacy of response
- large magnitude of exercise
- tight matching of response to metabolic rate
arterial gas tensions during sub maximal exercise
remain constant, despite increases in metabolic rate
metabolic rate in terms of ventilation
VO2 and VCO2
are arterial gas tensions maintained beyond the anaerobic threshold
no; pH and PaCO2 decrease because of acidoses and hyperventilation
how does PaCO2, PaO2 and pH remain constant in sub maximal exercise
breathing increase is
- immediate at onset of exercise
- has magnitude proportional to change in metabolic rate
- O2 delivery to muscles in CV system is proportionate to workload and VO2
what controls the breathing response to exercise?
poorly understood:
- no error signal for chemoreceptors bc PaCO2, PaO2 and pH remain constant
- there are changes in the venous blood, but that isn’t where chemoreceptors are located
?????
speculations of how breathing response to exercise is controlled
- mixed venous chemoreceptors, would be perfectly located to detect changes in metabolic rate, but none have been found
- neural feedback from skeletal muscle afferent nerves
- neural feedforward signals from motor regions in the brain; central command
- humeral stimuli from blood-born factors; circulating K+, adrenaline, , which could increase chemoreceptor sensitivity to minute changes o PaO2 and PaCO2
multiple mechanisms responsible for breathing response to exercise
neural-humoral theory
argued that only a mixture of mechanisms could explain the characteristics of breathing response:
- neural mechanism responsible for immediacy of response in phase I
- humoral mechanism responsible for fine tuning of response to tightly match ventilation with metabolic rate
neural-humoral theory
breathing response to exercise
evidence for neural mechanisms of breathing response
feedforward central command, and neural feedback mechanisms of skeletal afferent nerves are known to be important in CV control
- evidence suggests the control CR too
evidence for humoral mechanisms
not PaO2, PaCO2 or pH cus they don’t change in sub max exercise
- increase in sensitivity of chemoreceptors, giving a bigger response to same stimuli - conflicting data and only small effect size
- plasma K+ and adrenaline increase in exercise and experiments suggest they case increased ventilation, but very small effect size
conclusions of breathing response to exercise
- ventilation is closely matched to work load and respiratory control mechanisms exist that maintain arterial blood gas homeostasis
- unsure how this is coordinated but like likely central command feed forward and muscle afferent feedback play a role
- likely that no single proposed mechanism accounts for the response
- element of redundancy
VO2 measured at mouth during exercise
rises linearly with work rate during an incremental exercise task
- because oxygen consumption of working muscles increases
how is increased VO2 in active muscles achieved
- central mechanisms which increase CO
- peripheral mechanisms which redistribute blood to exercising muscles
- all occur along side respiratory response
CV responses during dynamic whole body exercise
- HR and stroke volume increase = increase CO - increase vasodilation of active muscles -some vasoconstriction of inactive muscles = decreased TPR - increased CO - decreased TPR = increased MABP
what happens to systolic BP during exercise
increases as stroke volume increases
what happens to MABP during exercise
increases as CO increases and TPR decreases
what happens to diastolic BP
remains constant because of balances vasodilation and vasoconstriction of active and inactive muscles (redirection of blood flow)
CV response to dynamic incremental exercise
- linear increase in HR with work loud
- increase in stroke volume, then plateaus
- close to linear increase in CO
- Decrease in TPR due to muscle vasodilation
- increase in SV tends to increase SBP
- TPR tends to keep DBP constant, but may decrease
- MABP increases moderately because = CO x TPR
why does vasodilation and vasoconstriction both occur
must have a balance
- vasodilation increases O2 delivery to working muscles
- vasoconstriction maintains BP
what would happen to MAP without vasoconstriction
MAP would plummet becuase of widespread vasodilation of other beds and increase in CO
what controls CV response to exercise
- autonomic nervous system
- local mechanisms
role of autonomic nerves system in CV response to exercise
- controls increase in HR, SV and vasoconstriction of inactive muscle and other orgas
role of local mechanisms in CV response to exercise
controls increased vasodilation in working muscles
- e.g build up of muscle metabolites
how is HR increased during exercise
ANS
combination of:
-reduced vagal/parasympathetic stimulation of SA node
- increase beta adrenergic sympathetic stimulation of SA node
how is stroke volume increased in exercise
ANS
- increased sympathetic activity to:
- increase central venous pressure
- increase ventricular contractility
how does increased central venous pressure result in increased stroke volume
-decreased venous compliance
- increased atrial contractility
= force of contraction via frank starling mechanism
CO during exercise
increased total CO, and additional blood flow carefully redirected to where it is needed
role of vasodilation during exercise
at active muscle for oxygen delivery
at skin for thermoregulation
role of vasoconstriction during exercise
of inactive muscles and other tissues to maintain BP
what drives vasodilation in exercise
local mechanisms
what rives vasoconstriction in exercise
widespread increase in sympathetic vascular tone (ANS)
what controls the ANS in exercise
multiple mechanisms, hence complex response
- feedforward via central command
- reflex feedback via:
- -metabolically and mechanically sensitive skeletally muscle afferents
- arterial baroreceptor afferents
= coordinated autonomic adjustments to increase HR, SV, CO, BP and arterial resistance
central command
concept that the higher brain simultaneously activates two seperate networks:
- neuromotor control systems of active skeletal muscles
- autonomic neural control of CV system & possible respiratory control centres
theory of feedforward central command
theorised that the CV system can anticipate the demands of exercise and so is a feedforward control mechanism
concept for feedforward
- Krogh and Lindhard
- HR and ventilation increase immediately with dynamic exercise
- immediacy suggests not a feedback mechanism
two methods for assessing feedforward CC theory
- uncoupling motor drive of CC from muscle force/work
- identifying neurocircitry of CC
Uncoupling motor drive of CC from muscle force/work
isometric handgrip exercise performed with and without neuromuscle block NMB, curare
- with NMB, attempted hand grip produced almost zero force as forearms effectively paralysed
- in these conditions, CC mechanism won’t be affected but there will be no neural feedback from muscle as no force produced
- NMB attempt resulted in similar HR response to normal contraction, but smaller increase in MSNA and MAP
= suggests that CC has greater role in regulation HR in these workloads
curare
neuromuscular block
NMB
neuromuscular block, e.g curare
Identifying the neurocircuitry
cat was stimulated in the sub thalamic motor region
= increased BP during spontaneous locomotion
cat was the paralysed, therefore no neural feedback from muscle for movement
- cat stimulated again and there was a CV and respiratory response even though cat didn’t more
summary of central command theory
- feedforward thought to provide instant and gross matching or CR responses to metabolic needs
- compelling but indirect evidence that CR system controlled by feedforward too
- animal evidence strong
- hard to obtain evidence in humans
- evidence that other mechanisms also play a role
reflex feedback control of CV response to exercise evidene
Alam and Smirk 1963 used PECO experiment to show that ANS is modulated by not just feedforward. PECO showed that metabolites trapped in muscle were driving an exercise pressor reflex EPR
PECO
Post Exercise Circulatory Occlusions
animal studies demonstrated that group III and IVE afferents in muscle are responsible for EPR
- stimulating ventral roots results in muscle contraction and increased BP
- PECO sustains BP
-cutting dorsal root afferents abolishes the BP response (GI-IV)
- BUT selective blocking of thinly myelinated and non-myelenisted fibres (III-IV) via local anaesthetic did abolish the response
- Group III and IV afferents drive EPR
which group fo afferents dove EPR
III and IV
what is EPR
exercise pressor reflex
anatomy of Group III afferents
- thinly myelinated
- largely mechanosensitive
- passive muscle stretch in humans causes:
- vagal withdrawal (PNA)
- increases in HR
PNA
parasympathetic neural activity
SNA
sympathetic neural activity
Anatomy of group IV afferent
- non-myelinated
- largely metabosensitive
- PECO in humans results in
- large insures in SNA and BP
- effect on HR debated
which fibres are metabosensitive
Grou IV
which fibres are non myelinated
group IV
Which fibres are mechanosensitive
Group III
which fibres are thinly myelinated
Group III
recent evidence for afferent feedback
injection of opiod agonist fentanyl inhibits feedback fro III and IV sensory efferents
reduced HR and MAP during cycling at different workloads
reduced ventilatory response despite similar VO2
summary for afferent feedback mechanism
- provide sensory feedback on conditions of working muscle
- compelling evidence that CV system is partly controlled by skeletal muscle afferent feedback … and may drive respiratory response too
- attractive mechanism bc accounts for rapid CR response at onset, along side CC, and how metabolic rate is matched
- stimulation can results in increased SNA and reduced cardiac PNA = increased HR and BP
vascular tone control mechanisms for muscle blood flow in exercise
- neural
- endothelial
- hormonal
- myogenic
- metabolic
neural vascular tone
sympathetic adrenergic fibres: - vasoconstrictor - alpha and beta sympathetic cholinergic fibres: - vasodilator
hormonal vascular tone
adrenaline and noradrenaline
endothermic effects on vascular tone
Nitrix oxide
prostaglandins
EDHP factors
myogenic effects on vascular tone
pressure response of vascular smooth muscle
metabolic effects on vascular tone
- potassium
- adenosine
- H+/pH
- lactate
- hypoxia
peripheral resistance to blood flow is dependent on
radius of the vessel which is regulated by the tone of vascular smooth muscle
what regulates the radiator of vessel
tone of vascular smooth muscle
what initiates contraction in VSM
mechanical, electrical an chemical stimuli
sympathetic control of muscular tone
- sympathetic nerves innervate arteries and veins
- most are adrenergic releasing noradrenaline for vasoconstriction
- important for maintaining BP in exercise
- local mechanisms predominate in the exercising muscle causing vasodilation
- increase MSNA in active muscle keeps TPR in check so MABP doesn’t drop
MSNA
muscle sympathetic nerve activity
what do adrenergic sympathetic nerves release
Noradrenaline which stimulates a1 and a2 adrenergic receptors to mediate vasoconstriction
metabolic control of muscular tone
- metabolites act directly on the VSM to decrease tone by vasodilation
- metabolites act indirectly by inhibiting SNA vasoconstriction, which further promotes vasodilation
what organs have variable metabolic rate
heart, brain, skeletal muscle
how is flow graded in organs with variable metabolic rate
flow is graded with tissue metabolism
what is direct action of metabolites for muscular tone
directly act on vascular smooth muscle to decrease tone
decreased tone
vasodilation
what is the indirect action of metabolites for muscular tone
indirectly act, by inhibiting SNA mediated vasoconstriction which means vasodilation is promoted
what are the metabolites that effect muscular tone
No one factor is sufficient on its own to account for all the increase in blood flow - cocktail effect
H+, K+, adenosine, lactate, AP etc
endothelial control of muscle vascular tone
Nitric oxide and prostaglandins are released in response to:
- chemical stimuli like ATP and Ach
- frictional drag force of blood across the vessel surface (sheer stress)
= vessels dilate in response to increased blood flow
interactions between metabolic and endothelial dilation , and sympathetic constriction
- downstream: vasodilation occurs through metabolic factors
- upstream: vasodilation occurs by endothelial factors because metabolites cannot reach here
increased muscle tension with constant muscle length
isometric/static exercise
rhythmic cycles of contraction and relaxation with muscles changing length
dynamic exercise
summary of CV response to Dynamic exercise
- high demand for O2 = increased CO, by increased HR and SR
- increased SV from increased SNA to the heart and increased venous return from muscle pump
- decreased TPR due to active muscle vasodilation
- increased systolic BP
- same or slight lower diastoli BP
- modest increase in MAP
summary of CV response to isometric exercise
-modest demand for O2 results in small change in CO mainly from increased HR
- reduced SV bc:
- increased TPR from local vasodilation being overrides by sustained mechanical compassion of vessels and impeded venous return and blood flow
- valsalva manoeuvre
- increase SNA induces vasoconstriction in on active muscle
- increased TPR
- increased diastolic, stoic and MABP
valsalva manoeuvre
closing mouth and holding nose and blowing helps restore normal heart rate if beating too fast
- causes build up of pressure
phases of heavy weightlifting
I) mechanical compression of blood vessels cause rise in intramuscular pressure to up to 1000mgHg
II) valsalva manoeuvre
III) exercise pressor reflex
blood pressure can rise to extremes e.g 480/350mmHg
what increases during dynamic exercise
HR, venous return, atrial filling and stroke volume
where is increased CO redistributed
active working muscles
what causes vascular beds of inactive tissues to dilate
local mediators / metabolites
what helps maintain BP alongside increased CO
SNA
why does isometric exercise have different CV response
mechanical compression of contracting muscle can override metabolic vasodilation
CV response is regulated by
both feedforward CC and feedback reflex
