What does total peripheral resistance mean?
Combined resistance of resistance vessels which determine distribution and flow;
measurement of the difficulty of blood leaving vessels.
What is blood draining into the veins determined by?
The balance between:
Rate at which blood enters the veins
Rate at which the heart pumps it out
This all determines how distended the veins become in particular the central veins.
What happens when total peripheral resistance changes and cardiac output remains the same?
When TPR decreases (easier for blood to leave the arteries), arterial pressure will fall (does not have to rise as high to push the same amount of blood out), venous pressure will rise (alters in opposite direction).
When TPR increased, arterial pressure will rise and venous pressure will fall.
What happens if cardiac output changes and TPR stays the same?
If cardiac output rises and TPR does not change (more blood is pumped through a given resistance), arterial pressure will rise and venous pressure will fall (as more blood is removed from the heart to be pumped out).
If cardiac output falls, arterial pressure will fall and venous pressure will rise.
Describe changes in demand for blood
TPR is inversely proportional to the body's need for blood.
Within individual tissues, the actions of vasodilator metabolites and other mechanisms will modify flow resistance through arterioles to suit metabolic demand.
Across the whole body the effect of these mechanisms is to make up the total peripheral resistance.
If metabolism changes, TPR changes and generates signals in the form of changes in arterial and venous pressure.
What happens after eating a meal?
The gut needs more blood.
Gut tissues produce local vasodilators which dilate arterioles.
Total peripheral resistance falls.
If cardiac output does not change, arterial pressure will fall due to decreased total peripheral resistance and venous pressure will rise.
Blood pressure may drop so low fainting could occur.
What is demand-led pumping?
If the body needs more blood, the heart needs to pump more to meet the demand.
Demand is expressed as changes in arterial and venous pressure signals.
Heart is sensitive to these changes therefore it is able to meet demand and restore pressures back to normal.
If the heart responds to falls in arterial pressure and rises in venous pressure by pumping more blood, then it will meet the demand and bring arterial and venous pressures back to normal.
What is Stroke Volume?
The difference between: End diastolic volume (after filling during diastole) and End systolic volume (after contraction during systole).
Note: ventricles rare fill to the maximum volume - max diastolic volume.
What happens during ventricular filling?
In diastole the ventricles are isolated from the arteries (valves are closed) and connected to the veins.
Venous pressure drives blood into the ventricles.
The ventricle fills as the walls stretch passively until the intra-ventricular pressure is equal to venous pressure (at this point there is no pressure gradient driving the filling of blood therefore ventricular filling stops).
Describe the relationship between venous filling and ventricular volume
The higher the venous pressure, the more the heart fills in diastole (within limits).
Venous pressure alters stretch of muscle fibres.
As increased blood causes ventricles to rub against rigid pericardium, curve becomes more steep.
Relationship between venous pressure and ventricular volume is known as the ventricular compliance curve.
Stroke volume increases if venous pressure increases.
Stroke volume is determined by how much the ventricles contract during systole. All myocardial cells normally contract so active tension is changed by factors which act directly upon individual myocardial cells. Discuss the mechanical factors acting on the myocardium.
Because of the valves, the mechanical forces are different in diastole and systole.
In diastole, the ventricle is connected to the veins so venous pressure determines the end diastolic stretch or 'pre-load' on the myocardium.
Once systole begins, the ventricles are isolated from the veins but connected to the arteries and the force necessary to expel blood into the arteries or the 'after load' determined what happens during systole.
Preload and afterload may vary independently.
What is Starlings Law?
If ventricular muscle is stretched (I.e. The more it fills) before contracting (the preload is increased), it contracts harder (up to a limit) during systole.
Therefore if all other things are equal, increases in venous pressure and therefore in end diastolic volume will lead to increases in stroke volume (the harder it contracts the bigger the stroke volume).
Rise in venous pressure automatically lead to rises in stroke volume
The heart responds to changes in venous pressure by pumping more or less blood (altering stroke volume). "More in more out!"
What is the Starling Curve?
Relates stroke volume to venous pressure
Slope is known as the contractility of the ventricle.
Increase in contractility --> increase in stroke volume.
The extent to which the increase in force of contraction is related to the increase in venous pressure.
What does afterload determine?
The effect of a given force of contraction during systole.
If it is easy to eject blood then the volume in the ventricle will fall a lot in systole but pressure will only rise a little.
Therefore falls in total peripheral resistance increase stroke volume by reducing after load.
If it is difficult to eject blood because blood will not readily leave the arteries (TPR high), then the stroke volume will be less but a much higher arterial pressure will be generated.
What is the End Systolic Volume dependent on?
How much the ventricle empties depends on:
How hard the ventricle contracts (the harder it contracts, the more it ejects).
How hard it is to eject blood (for a given force of contraction)
What is the force of contraction determined by?
End diastolic volume (according to Starling's law: the more heart fills the harder it contracts)
Contractility (slope of curve relating stroke volume to venous pressure).
Contractility is increased by sympathetic activity (so more blood is ejected). Heart failure reduces contractility.
What does aortic impedance depend on?
Total peripheral resistance
The harder it is to eject blood the higher the pressure rises in the arteries
Aortic impedance also depends on stretchiness of artery.
What happens if arterial pressure falls?
The easier it is to eject blood, the more comes out in systole so if arterial pressure falls, end systolic volume will fall and stroke volume will rise.
What are the chemical factors that can affect contractility (dependent on intracellular [Ca2+})?
The force of contraction of the ventricle always arises with pre-load but the slope of this relationship - the contractility - can be affected by neurotransmitters, hormones or drugs acting on the myocardium.
Noradrenaline and adrenaline increase contractility (how much calcium is available intracellularly) (positive inotropy) so increases in sympathetic activity will increase stroke volume at a given pre-load and after load.
What are the direct effects of arterial and venous pressures on stroke volume?
If venous pressure rises, stroke volume will rise
If arterial pressure falls, stroke volume will rise
Describe the control of Heart Rate
Sympathetic activity increases HR
Parasympathetic activity decreases HR
At rest parasympathetic activity predominates (~60bpm)
Increases in heart rate can be produced by turning off the parasympathetic system and increasing sympathetic stimulation.
The ANS can therefore influence cardiac output by changing heart rate and contractility (sympathetic branch only)
What do baroreceptors do?
Monitor arterial blood pressure.
Located in the walls of the aorta and the carotid sinus at the bifurcation of the common carotid artery, they detect changes in arterial pressure.
This information is released to the medulla where collections of neurones - the cardiovascular centre- modify the behaviour of the heart and circulation via the ANS.
What happens when Baroreceptors detect falls in arterial pressure?
Increase heart rate by reducing parasympathetic activity and increasing sympathetic activity
Increase contractility by increasing sympathetic activity.
So heart rate and stroke volume (dependent on two independent factors: contractility and preload) rise.
So via the ANS, falls in arterial pressure increase cardiac output.
What happens when venous pressure rises?
Sensed by receptors in right atrium and great veins which lead to reduced parasympathetic activity and so a rise in heart rate.
A rise in venous pressure also increases stroke volume (Starlings Law)
This is known as the Bainbridge reflex but this a minor effect of venous pressure on heart rate.
What happens if TPR falls?
Then arterial pressure will fall and venous pressure will rise.
The heart will respond by pumping more which will increase arterial pressure and reduce venous pressure so restoring the status quo - a stable system.
What is the effect on cardiac output when venous pressure rises or arterial pressure falls?
Cardiac output RISES
Rules of the CVS: at a constant cardiac output
Falls in TPR INCREASE venous pressure and DECREASE arterial pressure.
Rises in TPR INCREASE arterial pressure and DECREASE venous pressure.
Rules of the CVS: at a constant total peripheral resistance (at a given value)
Increases in cardiac output DECREASE venous pressure (more blood is removed from the veins) and INCREASE arterial pressure (more blood is pumped into the arteries).
Decreases in cardiac output INCREASE venous pressure and DECREASE arterial pressure.
Rules of the CVS: how do changes in arterial and venous pressure affect cardiac output?
Increases in venous pressure increase cardiac output
Decreases in arterial pressure increase cardiac output
How does arterial pressure changing affect total peripheral resistance and venous capacitance?
Falls in arterial pressure increase total peripheral resistance to certain tissues (non-critical organs such as skin and gut, which can tolerate a lower blood supply than their metabolism demands temporarily).
Falls in arterial pressure lead to veno-constriction of smooth muscle in the walls of veins reducing venous capacitance.
This compresses the veins and temporarily increases the pressure within the veins.
What do the CVS rules do?
Temporarily stabilise the system.
Protective short term mechanism in order to protect critical organs from an insufficient blood supply (which would be very damaging) by re-distributing blood.
The rules allow prediction of how the CVS will change in the short term under different circumstances.
What happens when an individual at rest eats a meal?
Increased activity of the gut leads to local vasodilation (production of vasodilator mediators and metabolites by the wall of the gut and other tissues) so local resistance falls as extra blood tries to flow to gut.
Total peripheral resistance falls which leads to increased venous pressure and decreased arterial pressure (easier for blood to leave the arteries).
Rise in venous pressure causes a rise in cardiac output (increased venous pressure --> increased stroke volume - Starlings Law).
Ventricular filling increases so the heart muscles contract harder and more blood is ejected during systole.
The fall in arterial pressure is detected by baroreceptors which triggers a rise in heart rate and stroke volume --> cardiac output increases.
The resulting increased cardiac output reduces venous pressure (venous pressure is reduced by extra pumping of the heart) back down to normal and raises arterial pressure back up to normal
Heart responds automatically; Demand - extra blood flow to gut - is met and the system is stable - blood flow to other organs is not compromised.
Total flow through the CVS rises and falls automatically with changes in metabolic demand.
Describe the changes in heart rate alone (in an artificial environment, e.g. After heart surgery, patient is on a pacemaker)
If heart rate increases with no other change, initially cardiac output will tend to rise but total peripheral resistance remains the same (due to no change in the metabolic activity - no increase in demand).
The increase in cardiac output reduces venous pressure so stroke volume falls (filling of the heart steadily reduces as there's less pressure to drive blood into the heart) and cardiac output returns back to original value (despite elevated heart rate).
This shows that the heart cannot drive the circulation - the circulation drives the heart (as far as the systemic circulation is concerned).
If the heart cannot drive the circulation (as far as the systemic circulation is concerned), what can change the cardiac output?
Change in the metabolic need of the body.
What happens to the pre-capillary sphincters as soon as you begin to exercise?
In skeletal muscle, local vasodilators produced act on local resistance vessels (pre-capillary sphincters).
Each fibre is adjacent to a capillary - has its own blood supply.
If the muscle is not active, most capillaries have no blood supply due to contraction of the pre-capillary sphincter - blocks the blood supply.
As soon as you begin to exercise, pre-capillary sphincters open up and this produces a huge fall in resistance - to allow huge amount of blood to flow through.
This reflects a rapid drop in total peripheral resistance.
Exercise produces a large increase in metabolic demand for blood flow. What happens?
As exercise begins, there is massive vasodilation in muscles which tends to produce a large fall in arterial pressure.
The fall in TPR and 'muscle pumping' tends to produce a large rise in venous pressure.
Muscle pumping drives extra blood back to the heart.
In the absence of other mechanisms, the fall in arterial pressure + TPR and increase in venous pressure would be so great that the heart would be driven to the top of the Starling curve by the venous pressure changes. How?
Venous pressure would rise greatly.
Arterial pressure and TPR would fall greatly.
These changes may be too big to cope with.
The great increase in venous pressure is the main problem as it tends to overfill the heart - pushes the ventricles onto the flat part of the Starling curve
.The heart is so full that further expansions do not trigger an increase in cardiac output and may trigger a decrease in cardiac output - starling curve is no longer useful as control mechanisms are no longer working properly because of the magnitude and rapidity of the change.
Why is there a risk of pulmonary oedema when there is ventricular overfilling?
The outputs of the right and left ventricles cannot be matched due to the sudden rush of blood returning to the left ventricle.
The two ventricles have different amounts of muscle.
Both sides of the heart beat at the same rate so can only match by matching stroke volume - which relies on a Starling curve; if the right heart pumps more, the left heart fills more and so pumps more.
But if on the top of the Starling curve, left heart can't respond to the right so blood accumulates in the lungs (pulmonary oedema) - the pressure in the lungs forces fluid into the interstitial space in the lungs from the circulation.
Blood is being pumped faster into the lungs than blood is being removed because the left side of the heart cannot respond.
How is overfilling of the ventricles prevented in normal individuals?
By a rise in heart rate at the onset of exercise, triggered by activation of the sympathetic system.
This rise occurs before large changes in arterial and venous pressure so the rush of blood returning to heart at the onset of exercise is preceded by a rise in heart rate which prevents venous pressure riding by pumping the extra blood immediately into the arteries.
Heart can cope with extra blood and keep the stroke volume down.
This 'pre-emptive strike' on heart rate presents large changes in arterial and venous pressure at the onset of exercise; sympathetic reflexes therefore maintain the system in the optimal state for other regulatory mechanisms to operate.
This is how we cope with intense exercise.
Describe what happens when we stand up
Blood 'pools' in the superficial veins of the legs because of gravity so central venous pressure falls (transiently); the effect of gravity increase transmural (the pressure within) pressure of the superficial veins in the lower extremities
These superficial veins are partly surrounded by air so gravity acts upon it less.
The pressure within the vein becomes substantially greater than the pressure outside the vein so the veins swell up. The veins are holding more blood.
This blood has not returned to the heart (so central venous pressure - the pressure within the great veins falls).
What happens when the central venous pressure falls after standing up?
By Starlings law, cardiac output falls (due to decrease in venous pressure relating to decrease in stroke volume) so arterial pressure falls.
Now both arterial and venous pressures are changing in the same direction which cannot be corrected by normal mechanisms and is a potentially dangerous situation.
Baroreceptors detect fall in arterial pressure and signal to raise heart rate but venous pressure is still low.
What changes do Baroreceptors trigger (when they detect the fall in arterial pressure and signal to raise Heart Rate) after standing?
Baroreceptors trigger rise in heart rate, vasoconstriction (therefore reducing blood flow) in skin and gut (sympathetic activity stimulating) to increase total peripheral resistance (so the venous pressure increases) and venoconstriction to drive more blood back towards the heart.
TPR is increased (by reducing blood flow to certain tissues such as skin and gut) to stabilise arterial pressure and maintain perfusion of vital organs such as the brain, but at the temporary expense of reduced blood flow to some tissues"
Changes in venomotor tone and flow through non-essential organs can be used to stabilise the system.
What is postural hypotension?
Low blood pressure - happens when blood pressure drops when you rise from a lying position to a standing position.
When reflexes don't work.
What happens to venous pressure when there is a haemorrhage?
70% of blood volume lies in veins so normally venous volume is lost from wounds - reduced blood volume lowers venous pressure (less blood in the venous capacitance).
So cardiac output falls (according to Starlings law) - the heart fills less, heart pumps less. TPR hasn't changed at this point.
Arterial pressure falls which is detected by Baroreceptors which signal to raise HR. Total peripheral resistance is increased - marked vasoconstriction.
But rise in heart rate lowers venous pressure further - making problem worse - low venous pressure is exacerbated both by attempts to raise cardiac output and the rise in total peripheral resistance.
What can happen as a result when venous pressure is lowered further during a haemorrhage?
Heart rate can become very high (vicious cycle)
Very rapid feeble pulse (stroke volume is low because there is low pressure to drive the heart)
White appearance (blood supply to shut down as much as possible especially to tissues at the skin)
Evidence of sympathetic activity - sweating.
So rise in TPR helps arterial pressure rise (so more blood is kept in the arteries) but lowers venous pressure so does not solve original problem.
In order to break the vicious cycle and survive the haemorrhage (if the haemorrhage is moderate), the venous pressure needs to be increased. How?
Veno-constriction of the muscles of the walls in the veins so blood is squeezed in the veins (increased venous pressure which drives blood into the heart) (physiologically)
Auto transfusion (fluid tends to move from extracellular space into the circulation so blood volume is gained); if the venous pressure goes down, hydrostatic pressure in the capillaries falls which causes fluid to move into the circulation which increases volume in the veins. The water, electrolytes and red cells are eventually replaced by homeostatic mechanisms which eventually replace blood volume lost (over time) and system stabilises again (as long as haemorrhage is moderate).
NOTE: control systems find it difficult to cope if arterial and venous pressure change in the same direction.
Describe the effects of a long term increase in blood volume
The kidney controls blood volume (by amount of sodium) so if blood volume increases for days (e.g. Due to changes in the kidney or diet), blood volume tends to increase so venous pressure increases (sustained).
Increased diastolic filling leads to increased cardiac output (due to increased stoke volume) which leads to increased, sustained arterial pressure.
At this stage TPR has not changed.
Compensatory mechanisms cannot bring cardiac output down.
How can you measure central venous pressure?
Measuring jugular venous pulse in the neck
What is average arterial pressure?
Determined by the volume of blood.
The higher the volume of blood, the higher the arterial pressure.
In the long term, the kidneys control the arterial pressure (depending on balance of sodium and fluid).
What is the effect of increased cardiac output when there is a long term increase in blood volume?
Increased CO forces more blood into the tissues which auto-regulate (through blood vessels contracting, increasing peripheral resistance - increasing arteriolar tone to return blood flow to normal).
But arterial pressure increases even more and stays up.
If the blood vessels go on contracting for a longer period of time, arterioles get bigger and stronger and contract harder so TPR stays elevated.
Cardiac output returns more or less to normal but arterial pressure is permanently raised (hypertension).
Turbulent and rapid flow damages arteries and causes problems in the circulation - very dangerous.
What is the long term effect of long term increase in blood volume
Blood volume control mechanisms control mean blood pressure; the sustained increase in arteriolar tone in many vascular beds leads to long term changes in resistance vessel walls, which render the TPR more or less permanent, so arterial pressure is now persistently elevated.
Reversal of the rise in blood volume will, particularly in the early stages, reduce blood pressure back towards normal.
This is achieved with diuretics, which alter the body sodium balance by interaction with the hormonal control of kidney.
What is Mean Filling Pressure?
Pressure in the arteries and veins when the heart stops.
Why at the top end of this 'Starling Curve', does stroke volume fall with increasing venous pressure?
The muscle fibres reach a critical length beyond which they are unable to contract efficiently.
This may be due largely to the passive stiffness of cardiac muscle fibres.
What is the physiological range for central venous pressure?
What factors can increase or decrease central venous pressure?
- Physiological range: 1-10mmHg
- Factors increasing CVP: venoconstriction, transfusion (increasing blood volume)
- Factors decreasing CVP: orthostasis (postural hypotension), factors lowering blood volume e.g. haemorrhage or dehydration
- CVP depends on the total blood in the circulation and the distribution of the blood.
What mechanism ensures that the right and left side of the heart pump the same amoutn of blood per minute?
- Frank-Starling mechanism matches venous return to cardiac output.
- Increased cardiac output in one ventricle automatically increases the venous return to the other ventricle.
- The consequent increase in myocardial diastolic fibre length in this ventricle results in an increased output which would match the other side.
What is Contractility?
The force of contraction for a given fibre length.
The force of contraction of the ventricle depends on both contractility and fibre length.
Under what circumstances might a sudden increase in parasympathetic activity to the heart occur? Why might this be dangerous?
- Cold ice on the face or plunging into cold water could cause sudden slowing of the heart rate and collapse. This can sometimes be a factor in drowning.
- Valsalva manoeuvre e.g. coughing, straining increases parasympathetic activity and can slow heart rate.
- Carotid sinus massage also increases parasympathetic activity to the heart
What happens to the output of the baroreceptors if htere is a sustained rise in arterial pressure lasting hours or days?
They 'reset' at a higher level
(Baroreceptors are good at controlling short-term changes in BP, but are not so effective over longer timescales as they rese).