The control of arterial blood pressure Flashcards
How is ABP relates to other factors
The mean arterial blood pressure (ABP) is the principal variable controlled by the cardiovascular system. By
keeping ABP constant, blood flow to individual tissues can be regulated simply by controlling the local arteriolar resistance, and the circulation thereby approximates a constant pressure / variable flow system. Its principal determinants are Cardiac Output (CO) and Total Peripheral Resistance (TPR).
Physiological and pathological
processes cause significant changes in TPR and CO; for example, exercise greatly reduces TPR, and blood loss
reduces MSFP and hence CO. Thus, control processes are necessary to maintain a relatively constant ABP.
Arterial blood pressure (ABP)
During each cardiac cycle, the heart rapidly ejects
blood into the aorta, causing the pressure to rise to
a peak called the systolic blood pressure, which is
normally about 120 mmHg (Figure 16). This creates
a pressure gradient towards the rest of the
circulation, so blood flows away from the aorta and the aortic pressure reduces to a trough value, the
diastolic blood pressure of about 80 mmHg, before
the next heart beat raises pressures again to
systolic values (and this occurs about 2.5 billion
times in an average lifespan!) Note that the fall
from systolic to diastolic pressure is not smooth – a
so-called dicrotic notch exists. This results from a
little backflow of blood towards the end of systole
(seen as a negative flow in the left-hand panel) as
pressures in the aorta begin to exceed those in the
ventricle, but which is quickly terminated by the
closure of the aortic valve, producing a small
“rebound” pressure wave.
Because of the shape of the pressure wave, the
mean blood pressure is approximately the diastolic
pressure plus 1/3rd of the pulse pressure.
The pulse pressure is the difference between the systolic and
diastolic pressures.
Mean blood pressure tends to increase with age,
and is slightly higher in men than women (between
puberty and menopause). The pulse pressure (i.e.
the difference between systolic and diastolic
pressure) can increase if arterial compliance
reduces, such as occurs
with atherosclerosis. The
pulse pressure also increases if blood can flow away faster in
diastole, as occurs
physiologically in exercise
(where TPR drops), or
pathologically if the
aortic valve leaks. In
situations where the
pulse pressure increases,
the mean pressure stays
constant (i.e. systolic
pressure rises as diastolic
pressure falls). This
strongly suggests that mean ABP is the principal
regulated variable. How is mean ABP regulated?
Regulation of mean ABP
From Darcy’s equation for the whole circulation:
ABP = CO x TPR
This highlights that anything which changes CO or
TPR will stress ABP control. It also shows that
control of CO or TPR can be used to control ABP.
TPR is primarily a function of arteriolar resistance,
and from Starling’s experiments, afterload (i.e. TPR
acting through changes in ABP) does not greatly
influence CO.
Thus, CO and TPR can be thought of
as largely independent of each other, providing two separate mechanisms for the regulation of ABP. In
order to regulate ABP, though, there must be
mechanisms for monitoring ABP.
Broadly, there are three mechanisms for
monitoring blood pressure: high pressure
baroreceptors; arterial chemoreceptors; and low
pressure baroreceptors. We will first look at the
various sites of blood pressure detection, before
considering how the signals from each are
integrated in the CNS to produce the overall
regulatory response.
High pressure baroreceptors
Arterial blood pressure can be sensed by
mechanoreceptors at strategic high-pressure sites.
These are the carotid sinus (just beyond the
bifurcation of the carotid artery) and the aortic arch
baroreceptors. In addition, the afferent renal
arterioles have an important baroreceptor function
that will be discussed in the renal physiology
lectures.
In each case, stretch-sensitive nerve
endings are intermeshed within elastic lamellae in
regions with relatively little collagen and smooth
muscle, such that stretch triggers increased activity
in baroreceptor fibres of the glossopharyngeal
nerve (carotid sinus) and vagus (aortic arch.) These
stimulate neurons in the Nucleus Tractus Solitarius
(NTS) in the medulla that inhibit the vasomotor
centre.
Different baroreceptor fibres have different
sensitivities to blood pressure, enabling groups of
fibres to cover quite large ranges in blood pressure,
from perhaps 50-200 mmHg (the** carotid sinus is
more sensitive than the aortic arch**, whereas the
aortic arch can respond at pressure above which
the carotid sinus response saturates.)
This was originally discovered in the 1920s:
Heymans won a Nobel Prize for showing that
increased blood pressure at the carotid sinus
produces a reflex reduction in blood pressure. He
did this in cross-circulation experiments with two
dogs, A and B. The carotid sinus of dog B was
connected into the circulation of dog A. Dog A was
injected with noradrenaline, increasing its blood
pressure, and this triggered a reflex fall in blood
pressure in dog B.
Denervation of arterial baroreceptors has an
interesting effect (see Figure 17): ABP becomes
much more variable, but mean ABP stays relatively
constant. This increased variability results from
such physiological stresses as changes in activity
level or changes in posture. This demonstrates the
importance of high-pressure baroreceptors and
chemoreceptors (see below) in the short-term
control of ABP. However, the constancy of mean
ABP suggests that it is regulated by other
mechanisms. Indeed, if mean ABP changes, high
pressure baroreceptors reset and regulate around
the new mean ABP.
Arterial and central chemoreceptors
Chemoreceptors in the carotid and aortic bodies
and in the medulla exist primarily to regulate
ventilation, as you will learn more about in the
respiratory lectures. They are not important in
blood pressure control under normal physiological
conditions. However, the arterial chemoreceptors
do have a role in ABP control when blood pressure
is very low or when PO2 is very significantly reduced.
Nevertheless, their responses may be important
because the high pressure baroreceptors are relatively unresponsive under conditions of severe
hypotension.
Under such extreme conditions, the carotid and
aortic bodies detect low O2 delivery, and the
medullary chemoreceptors detect high arterial CO2
via the resultant reduction in brain pH. The afferent
signals from the carotid and aortic bodies travel by
similar pathways to the baroreceptor signals from
the carotid sinus and aortic arch, i.e. the
glossopharyngeal nerve and vagus nerve
respectively.
Low pressure baroreceptors
The lack of influence of high pressure baroreceptors
and chemoreceptors on mean blood pressure
strongly suggests that longer-term control of ABP
involves other detection mechanisms. Due to the
importance of MSFP in the determination of ABP, it
is perhaps unsurprising that stretch receptors also
exist in strategic low-pressure areas of the
circulation: the junctions of the atria with their
corresponding veins and in the atria themselves.
Collectively, these are called the cardiopulmonary
baroreceptors.
These stretch receptors essentially detect RAP: if
RAP is raised, this suggests that the circulation is
over-filled such that the heart cannot maintain low
venous pressures. This is seen in heart failure and
can lead to oedema as capillary pressures rise.
Conversely, if RAP is low, this suggests that cardiac
output is maximal for the current MSFP.
Denervation of these receptors alongside
denervation of the arterial baroreceptors produces
a rise in mean ABP (Figure 18).
This contrasts with
the normal ABP seen with arterial baroreceptor
denervation alone (Figure 17).
The firing rate of these receptors increases with
pressure. The afferent signals travel via the vagus
nerve, to the **nucleus tractus solitarius **(NTS) in the
medulla, and thence to the hypothalamus. There,
they influence secretion of ADH, sympathetic
activity (especially the renal nerves), thirst, and
possibly sodium appetite. The net effect is that
reduced pressure produces fluid and sodium
retention, thereby raising the circulating volume
and MSFP. The details of these processes will be
covered in the renal physiology lectures next term.
Non-feedback control systems
Feed-forward with different part feeding into the medulla like cortex(decision making), joint and muscle receptor
Baroreceptors and chemoreceptors act within
feedback systems, and their importance is clear
from denervation experiments. However, common
stresses on ABP regulation such as exercise and
standing up, and even mild to moderate blood loss,
do not cause detectable drops in ABP, and so
cannot be entirely reliant on feedback. These
common stresses trigger feed-forward mechanisms
to preserve ABP.
Thus, a drop in ABP can be prevented in exercise by
inputs to the medulla from the cortex (where a
“decision” to exercise might be taken), from the
cerebellum (as part of a co-ordinated motor
“programme”) and from muscle and joint receptors
(as a direct response to movement).
Similarly, pain and emotions such as fear and anger
(involving the cortex and hypothalamus), can also
provoke a rise in blood pressure: essentially part of
the fight-or-flight preparation for dealing with
whatever one is worried or frightened of, and
perhaps helping the body to deal with any incipient
blood loss.
Integration of baroreceptor and “feed-forward”
signals in the medulla
Before this starts to look dauntingly complex, there
is some good news. The feed-forward mechanisms
feed into the same area of the brain – the
cardiovascular centre of the medulla – as the baroand chemoreceptors. A summary of the main
neural pathways for all these systems are
summarised below Figure 19.
The effector pathways
The medulla then generates a response, informed
by sensory input from the circulation as well as
more “strategic” inputs from higher brain centres.
This enables it to control ABP via two major efferent
pathways: the sympathetic and parasympathetic
divisions of the autonomic nervous system.
Sympathetic outflows act on the vasculature and
the heart, and the parasympathetic outflow is
solely to the heart. However, it is worth noting that
other autonomic pathways that will not be
discussed here are involved in the control of local
blood flow for specific processes, such as in
sweating, salivation and digestion.
Sympathetic efferents
Bulbospinal pathways (i.e. from the medulla to the
spinal cord) activate pre-ganglionic pathways,
primarily at glutamatergic synapses between levels
T1 and L3 of the spinal cord.
These pre-ganglionic
neurons synapse at nicotinic synapses with
postganglionic sympathetic neurons found within
prevertebral and paravertebral sympathetic
ganglia.
The postganglionic sympathetic nerves
involved in ABP control run with the large blood
vessels to innervate muscular arteries, arterioles
and veins. Increased sympathetic activity generally
causes vasoconstriction (including
venoconstriction) through the action of
noradrenaline on α1 adrenoceptors.
Arteriolar vasoconstriction increases TPR, while
venoconstriction increases MSFP. Sympathetic
activity also causes some redistribution of blood
flow, as the vasculature of some organs receives
little significant sympathetic vasoconstrictor
innervation: in particular, arteries and arterioles
supplying the brain and the heart show little if any
vasoconstriction during cardiovascular reflex
responses.
Sympathetic vasoconstrictor nerves are tonically
active, with a resting action potential frequency of
1-4 Hz. Their activity can increase to around 10 Hz
which can reduce blood flow to some tissues to
almost zero in extremis, such as in catastrophic
haemorrhage. The resting tone allows inhibition of
sympathetic activity (e.g. from the baroreceptor
reflex) to reduce ABP. It also means, for example,
that spinal cord damage above T1 causes a severe
and rapid drop in blood pressure by abolishing this
resting sympathetic outflow.
Sympathetic fibres also supply the heart (cardiac
accelerator nerves), innervating the SA node, atria
and ventricles. They increase both heart rate and
contractility, and have a low resting frequency.
Finally, some preganglionic sympathetic fibres in
the splanchnic nerves innervate the chromaffin
cells of the adrenal medulla. Their activity stimulates adrenaline release into the circulation,
which acts on the heart and vasculature in a broadly
similar manner to direct sympathetic innervation,
via α1 receptors. However, some tissues – notably
coronary blood vessels and skeletal muscle – have
more β2 than α1 receptors. β2 receptors trigger
vasodilatation, thereby increasing coronary and
skeletal muscle blood flow. However, note that
noradrenaline from sympathetic nerves primarily
acts on α1 receptors, which allows skeletal muscle
blood flow to be limited if necessary.
Parasympathetic afferents
The vagus nerve innervates the SA node, AV node
and the cardiac conducting system. Its activity slows
the heart rate and slows conduction through the
heart, lengthening the cardiac cycle. It does not
influence force. The vagal supply to the heart is one
of the rare parasympathetic pathways that shows
tonic activity. Inhibition of the vagus at rest, using
atropine, produces significant acceleration of the
heart rate.
Integration and effectiveness of circulatory control
There are many challenges to blood pressure
regulation in everyday life. Activities as diverse as
running, digestion, sweating and even thinking
require increased blood flow to specific organs or
systems that necessitate local vasodilatation (the
next lecture will cover how this vasodilatation
comes about). The resultant fall in TPR can be very
large: as much as five or six-fold in whole-body
intensive exercise. Yet, mean ABP stays relatively
constant (Figure 20).
Since ABP = CO x TPR, any fall in TPR would be
expected to produce a fall in ABP unless there was
an adequate response. Small adjustments can be
effected by sympathetic vasoconstriction of blood
vessels, and indeed some tissues such as skeletal
muscle, skin and the gastrointestinal tract receive
more blood that is required to meet their metabolic
demands at rest. However, any significant fall in TPR
demands an increase in CO. This ultimately requires
sympathetic venoconstriction to increase MSFP, in
concert with reduced vagal and increased
sympathetic stimulation of the heart, to increase
heart rate and contractility (ensuring raised MSFP
produces a rise in CO without necessitating an
increased RAP). Together, these manoeuvres
increase CO and hence maintain mean ABP.
It is important to note that this lecture concerns the
short-term control of blood pressure. Over longer
periods, the circulating volume is a critical
determinant of MSFP and hence ABP. You will learn
about its control in the renal physiology lectures.
Congestive cardiac failure
To understand heart failure, it is important to
understand what exactly the heart is failing to do.
In severe, end-stage heart failure, there is a failure
to adequately perfuse organs, resulting in organ
failure and eventual death if untreated. In less
severe heart failure, it is necessary to think more
carefully about the heart’s precise role.
On the most basic level, the heart’s role is to pump
blood from the veins to the arteries, so heart
failure implies that atrial pressure is too high, and
arterial pressure is too low. Then, it is necessary to
understand what constitutes “too high” atrial
pressure, and “too low” ABP. Too high atrial
pressure is straightforward: atrial pressure should
be close to zero, because if it is any higher it
impedes venous return and tends to raise capillary
pressures. A non-failing heart, by the Starling
mechanism, and assisted by sympathetic
stimulation in e.g. exercise, maintains RAP close to
zero.
What is “too low” ABP? This is slightly more
complicated, because it is quite possible – indeed,
very common – to find symptoms of heart failure
and hypertension in the same patient. This is
because heart failure develops when ABP is lower
than the set point and cannot be raised. The body
responds to this broadly as it does to haemorrhage
(see lecture 9 and the renal physiology lectures):
increased sympathetic drive causes
venoconstriction, arteriolar vasoconstriction, and
(with renal responses) retention of fluid. Together,
these raise TPR and MSFP. Normally, TPR does not
influence CO (Starling mechanism) but this may
not be true in a failing heart because maintaining
CO with increased TPR requires an increase in
cardiac work. Similarly, CO is normally limited by
MSFP (i.e. it is as high as it can be without raising
MSFP). In heart failure, CO is instead limited by the
heart, so raising MSFP will not produce a
significant increase in CO, but will instead cause
atrial pressure to rise. This is summarised in Figure
21.
The symptoms of heart failure primarily result
from 1) an inability to adequately increase CO; and
2) the increased atrial pressure. An inability to
adequately increase CO reduces exercise capacity
and may induce feelings of fatigue (see lecture 9).
Raised atrial pressure implies raised venous
pressures and hence raised capillary pressures.
This causes oedema: peripheral oedema in rightsided heart failure and pulmonary oedema in leftsided heart failure.
Understanding the physiology of heart failure is
key to understanding its treatment. Often, there is
little that can be done to improve cardiac output
(though valve repair, pacing, coronary bypass etc.
can be used to treat failure resulting from valve
disease, rhythm disorders and severe angina
respectively). However, drugs that inhibit the
responses to low blood pressure, such as
angiotensin converting enzyme (ACE) inhibitors
and diuretics, can produce significant symptomatic
relief, by lowering MSFP and TPR. Can you see how
this might both reduce oedema, and reduce
cardiac oxygen demand, perhaps even without
decreasing CO?
