stroke volume =
EDV - ESV
cardiac output =
SV x HR
blood pressure =
Q(cardiac output) x TPR(total peripheral resistance)
venous volume distribution is affected by?
peripheral venous tone, gravity, skeletal muscle pump and breathing
what does central venous pressure determine?
determines the amount of blood flowing back to the heart
this in turn determines stroke volume
flow is primarily changed by?
altering vessel radius
since constriction reduces compliance and venous return
F = (Poiseuille’s equation)
R inversely proportional to?
§ Remember the two important equations and relationships:
𝐹= Δ𝑃/𝑅
𝑅 ∝ 1/𝑟^4
Autoregulation =
Autoregulation = the intrinsic capacity to compensate changes in perfusion pressure by changing vascular resistance.
Myogenic Theory –
Smooth muscle responds directly to tension changes in the vessel wall e.g. stretch sensitive receptors.
Metabolic Theory –
As blood flow decreases, metabolites accumulate and vessels dilate in response.
Injury Theory –
Serotonin release from platelets causes vasoconstriction.
examples of local mechanisms regulating blood flow
autoregulation
myogenic theory
metabolic theory
injury
local endothelium derived hormones
- Nitric Oxide (NO) – vasodilation, produced from arginine, NO diffuses into vascular smooth muscle cells
- Prostacyclin- vasodilator, synthesised from prostacyclin precursor, also has an antiplatelet and anticoagulant effects
- Thromboxane A2 – vasoconstrictor, synthesised from prostacyclin precursor, also heavily synthesised in platelets
- Endothelins – POTENT vasoconstrictors. generated from the nucleus of endothelial cells- has minor vasodilator effects but principally a vasoconstrictor
circulating non-endothelium derived hormones
- Kinins: binds to receptors on endothelial cells and stimulate NO synthesis- vasodilator effects
- ANP (arterial natriuretic peptide): Secreted from the atria in response to stretch. Vasodilator effects to reduce BP.
- Circulating Vasoconstrictors: ADH/Vasopressin from posterior pituitary in response to high blood osmolality. binds to V1 receptors on smooth muscles and causes vasoconstriction.
Angiotensin II from renin secretion: potent vasoconstrictor product from the renin-angiotensin-aldosterone axis. Also stimulates SNS activity and ADH secretion.
Autonomic nervous system includes 2 branches
parasympathetic and sympathetic
SNS is important in?
SNS is important in controlling the circulation.
PNS is important in?
§ PNS is important in regulating heart rate.
Sympathetic innervation to blood vessels:
Sympathetic innervation to blood vessels:
§ SNS nerve fibres innervate ALL vessels except capillaries, pre-capillary sphincters and some metarterioles.
§ Distribution of fibres is variable, more fibres innervate vessels to kidney, gut spleen and skin and less innervate skeletal muscle and the brain.
pre-ganglionic fibres use what as their neurotransmitter?
ACh
PNS post ganglionic NT
ACh
SNS post ganglionic NT
NA
noradrenaline prefers to bind to what receptors?
preferentially binds to alpha-1 adrenoceptors to cause smooth muscle contraction/vasoconstriction.
Circulating adrenaline binds with high affinity to smooth muscle beta-2-adrenoreceptors to cause vasodilation in some organs, however the effect is very concentration-dependent
At high concentrations, adrenaline can bind to ALPHA adrenoreceptors which can override the vasodilatory effects of the beta-2-adrenoreceptor stimulation and produce vasoconstriction
The constriction you see in blood vessels is an alpha-1-adrenoreceptor effect
vasomotor centre location
VMC is located bilaterally in the reticular substance of the medulla and the lower third of the pons
The VMC consists of a:
Vasoconstrictor Area (Pressor)
Vasodilator Area (Depressor)
Cardioregulatory Inhibitory Area
what do each of the different parts do?
- higher centres of the brain
- lateral portions of the VMC
- medial portion of the VMC
Higher centres in the brain (such as the hypothalamus) can exert excitatory and inhibitory effects on the VMC
Lateral Portions of the VMC controls heart activity by influencing heart rate and contractility
Medial Portions of the VMC transmits signals via the vagus nerve to the heart that tends to decrease heart rate
The VMC allows an anticipatory response to exercise - your heart rate and ventilation rate will go up slightly before exercise because of these higher sensors in the brain
nervous control of vessel diameter- how does it work?
Blood vessels receive sympathetic postganglionic innervation
The neurotransmitter involved is NORADRENALINE
There is ALWAYS some tonic activity
At baseline, there is a certain frequency of the impulses which maintains vasomotor tone
If you increase the nerve traffic then you can constrict the vessel
If you decrease the nerve traffic then you can dilate the vessel
So by altering this activity you can make the vessel either dilate or constrict
There is NOT much parasympathetic innervation of the vascular system
Control of Blood Vessel Radius
THREE areas allow control of vessel radius:
Local Controls (Autoregulation)
Circulating Hormones
Sympathetic Vasoconstrictor Nerves
cardiac innervation by dual innervation
what are they and how do they work?
dual innervation - sympathetic and parasympathetic
The sinoatrial nodal cells receive sympathetic and parasympathetic innervation
Normal resting heart rate is around 70 bpm
Parasympathetic slows heart rate down because acetylcholine decreases the gradient of the pacemaker potential - this means that the potential takes longer to reach threshold and fire
Sympathetic increases heart rate because adrenaline and noradrenaline increases the gradient of the pacemaker potential so threshold is reached more quickly
If we cut the sympathetic nerves we lose the ability to increase heart rate so heart rate falls
with no cardiac innervation what is the normal activity?
100bpm
controlling force of contraction can be increased using which law?
Force of contraction can be increased by Starling’s Law
how does controlling force of contraction work using sympathetic activity?
Sympathetic activity will also increase the force of contraction
Noradrenaline binds to Adrenoreceptors which increases the amount of cAMP which activates PKA which phosphorylates the L-type calcium channels and the SR calcium release channel and SERCA
So you get MORE CALCIUM INFLUX and more calcium taken back up into the stores
Action of noradrenaline on beta-1-receptors in the heart will increase contraction
So we can alter heart rate and strength of contraction by sympathetic activity
Strength of contraction CAN NOT be changed by parasympathetic activity
controlling stroke volume by two methods
Increased Sympathetic Activity
Plasma Adrenaline
since:
Intrinsic control of stroke volume: venous return which sets the end-diastolic volume (stretch) which increases the force of contraction
We can get more blood back to the heart (increase venous return) if we increase respiratory movements - decreasing intrathoracic pressure helps the filling of the heart
what occurs as part of the flight or flight response?
We can get rapid changes in RESPIRATORY MOVEMENT, PLASMA ADRENALINE and INCREASE SYMPATHETIC ACTIVITY as part of the fight or flight response
where are baroreceptors located?
aortic arch and in the carotid sinus (carotid bodies)
Baroreceptors in the carotid bodies feedback to
Baroreceptors in the carotid bodies feedback to the vasomotor centre via the glossopharyngeal nerve
The aortic arch baroreceptors feedback to
The aortic arch baroreceptors feedback to the vasomotor centre via the vagus nerve
how do baroreceptors work?
change firing in response to arterial pressure
Carotid sinus baroreceptors respond to pressure between
Carotid sinus baroreceptors respond to pressure between 60 and 80 mmHg
Baroreceptor reflex is most sensitive around
Baroreceptor reflex is most sensitive around 90-100 mmHg
Increase in baroreceptor firing =
Increase in in parasympathetic activity as
When the receptor sees an increase in pressure it fires more - the nerve activity is increased
The sympathetic nerves are connected via a series of inhibitory interneurones which slows down the tonic activity
Increase in baroreceptor firing = DECREASE in sympathetic activity to heart, arterioles and veins
increased parasympathetic stimulation of the heart
decreases heart rate
where are cardioregulatory and vasomotor centres located
medulla oblongata
Increased Blood Pressure =
mechanics
huge increase in firing activity throughout from the baroreceptor
The increase in baroreceptor firing is fed back to the vasomotor centre which triggers increased traffic in the vagus nerve
REMEMBER: parasympathetic activity reflects exactly what happens in terms of baroreceptor activity
Increase in parasympathetic activity causes an increase in acetylcholine production in the SAN which decreases the gradient of the pacemaker potential and causes a decrease in heart rate
Increase in baroreceptor activity also decreases the sympathetic nerve traffic which also brings about a decrease in heart rate
Sympathetic cardiac nerves also have an effect on the force of contraction - so less innervation from sympathetic nerves leads to a decrease in the force of contraction
Decrease in sympathetic activity also leads to an increase in vessel radius
These changes in heart rate, contraction and dilation leads to a DECREASE IN BLOOD PRESSURE
which nerves are involved in control of venous return
sympathetic vasoconstrictor nerves
Mean Systemic Arterial Pressure =
Cardiac Output x Total Peripheral Resistance