L4: The control of arteria blood pressure

What is the mean arterial blood pressure ABP

• the pressure measured within large arteries in the systemic circulation

• split into systolic and diastolic blood pressure

Systolic blood pressure

→ 120mmHg normalling

• peak when heart ejects blood into the aorta

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…

Diastolic blood pressure

→ 80 mmHg

• the aortic pressure at a trough value

(before the heart beats raisess pressure again)

Why is the fall in pressure between the systolic and diastolic not smooth

• dicrotic notch exists:

  • pressure in the aorta begin to exceed those in the ventricle

  • pressue in aorta begin to exceed those in the ventricle

  • quickly terminated by the closure of the aortic valve

    • → produces a small ‘rebound’ pressure wave

What is the mean blood pressure? MAP

MAP: diastolic + 1/3(systolic-distolic)

note: pulse pressure= systolic-diastolic

How does MAP increase

1. with age

2. higher in men (between puberty and meopause)

3. Aortic valve leakage

BUT: ABP stays constant

Pulse pressure can increase if

1. arterial compliance reduces

   • e.g in atherosclerosis

2. if blood flow away faster in diastole

   • (i.e in exersise)

     • due to TPR drops

   • pathologically if valve leaks

3. Age

BUT ABP stays the same

But when the pulse pressure increases, what happens to MAP

• MAP stays constant:

  • i.e systolic pressure rises but diastolic pressure falls

• This strongly suggests that mean ABP is the principal regulated variable

This makes sense→ systolic may increases but diastolic must also fall

• this ensures that pulse pressure does increase

but

• MAP will stay constant

Why is ABP being the principal variable controlled by cardiovascular system, really useful?

• keeping ABP constant→ blood flow to individual tissues can be regulated simply be controlling the local Arteriolar resistance

• The circulation thereby approximates a constant pressure/variable flow system

How does ABP relate to CO and TPR

• CO and TPR are the principal determinants of ABP

  • physiological and pathalogical processes can change TPR

    • i.e exercise decreases TPR

    • blood loss reduces MSFP and CO

  • THEREFORE→ control processses are needed to maintain a relatively constant ABP

Rearranging Darcy’s equation for whole circulation

ABP= CO x TPR

• highlights that changing CO or TPR will stress ABP control

and also

• Changing CO or TPR can be used to control ABPR

Why are CO and TPR though to be largely indenependent

TPR→ primarily a function of arteriolar resistance

CO→ afterload does not greatly influence CO

THEREFORE: they provide two separate mechansims for regulation of ABP

However, in order to regulate ABP, we must be able to monitor it

Another reason why ABP is the prinipal variable controlled is coz

• CO and TPR cannot easily be monitored 

• but ABP can! 

Three feed-back mechanisms for monitoring blood pressure

Feed-back systems

1. high blood pressure baroreceptors

2. arterial chemoreceptors

3. low pressure baroreceptors

1. High pressure baroreceptors: what are they

• mechanoreceptors at strategic high-pressure sites

  1. Carotid sinus→ just beyond the bifuraction of the carotid artery

  2. Aortic arch

  3. also: afferent renal arterioles have one too

1. High pressure baroreceptors: structutre of the nerve

• stretch-sensitive nerve endings

• intermeshed within elastic lamellae

• inregions with relatively little collagen and smooth muscle

1. High pressure baroreceptors: what happens upon stretch

1. Triggers activity in baroreceptor fibres of

   1. glossopharyngeal nerve ←(carotid sinus)

   2. vagus ←(aortic arch) 

2. Stimulates neurons in the Nuleus Tractus Solitarius (NTS) in the medulla

3. This inhibits the vasomotor centre

1. High pressure baroreceptors: advantage of different baroreceptor sensitivies

• different baroreceptors have different sensitiviteis to blood pressure

• enables groups of fibres to cover LARGE ranges of blood pressure

  • 50-200 mmHg

1. High pressure baroreceptors: Carotid sinus vs aortic arch

• Carotid sinus is more sensitive than aortic arch

but

• Aortic arch can respond as pressure above which the arotid sinus response saturates (i.e Aortic is sensitive to higher pressures tha ncarotid)

1. High pressure baroreceptors: cross- circulation experiment to show increased blood pressure at carotid sinus produced a reflec reduction in BP

1. Carotid sinus of dog B was connected into the dog A circulation

2. Dog A injected with noradrenaline

3. increases blood pressure

4. triggered a reflex fall in blood pressure in dog B

1. High pressure baroreceptors: What happens on the denervation of arterial baroreceptors

1. ABP becomes much more variable

   • why: physiological stress → change in acitivty or posture

2. BUT: mean ABP stays relatively constant

1. High pressure baroreceptors: what does this suggest about their importance

1. Variability→ high-pressure baro and chemorepecots in the short-term  control of ABP

2. constant mean ABP→ suggests ABP is regulated by other mechanisms than the high-pressure repceotors

   • i.e if mean ABP changes→ high pressure baroreceptors reset and regulate to new mean ABP

     • thus, showing that these receptors are not responible for setting the mean ABP and are only short term

2. Arterial and central chemoreceptors: where are they

1. Carotid bodies

2. Aortic bodies

3. Medulla

4. Arteries

All but the arterial chemoreceptors mainly regulate ventilation:

• arterial do have a role in ABP control when blood pressure

2. Arterial and central chemoreceptors: role of arterial chemoreceptors

• role in ABP control when 

  1. blood pressure is very low

  2. Po2 is very significantly reduced

• role is important because the high pressure baroreceptors are relatively unresponsive under  conditions of severe hypotension

2. Arterial and central chemoreceptors: how they work

1. Extreme condisions

2. carotid and aortic boddies detect low O2 delivery

3. medullary chemoreceptors detect high arterial CO2

   • via the resultant reduction in brain pH

4. Afferent signals from the arotid and aortic bodies travel by similar pathways to baroreceptors signals

   • carotid sinus→ glossopharyneal

   • vagus nerve→ aortic arch

3. Low pressure baroreceptors: importance

• as high pressure baroand chemorecepetos do nothing on mean blood pressure

• strongly suggests that longer-term control of ABP involves other detection mechanisms

also:

• due to importance of MSFP in determining ABP

  • unsuprising that stretch receptors are exist in strategic low-pressure areas of the circulation

3. Low pressure baroreceptors: where found

strategic low pressure areas

1. junctions of atria with their corresponding veins

2. atria themselves

Cardiopulmonary baroreceptors

3. Low pressure baroreceptors: role

Especially detect RAP:

1. if RAP raised→ suggests circulation is over-filled

   • so the heart cannot maintain low venous pressures (so venous return will be lower)

   • i.e in heart failture and oedema as capillary pressures rise

2. if RAP low→ suggests that cardiac output is maximal for the current MSFP

3. Low pressure baroreceptors: what happens if denervated (and arterial baroreceptors denerved too)

• produce mean ABP rise

→ contrasts with the normal ABP seen with arterial baroreceptor denervation alone

3. Low pressure baroreceptors: how they work

1. pressure increase→ firing rate increases

2. afferent signals travel via vagus

3. to nucleus tactus solitarius NTS in medulla

4. to hypothalamus

5. can influence

   1. ADH secretion

   2. sympathetic acticty (esp. in renal nerves)

   3. thirst

   4. possibly sodium appetite

NET EFFECT→ reduces pressure→ produce fluid and sodium retention→ raising circulating volume and MSFP

Feed-forward mechanisms to preserve ABP: why needed

• common stresses on ABP regulation

• do not cause detectable drops in ABP

• so cannot be reliant on feedback

  • → need ABP to trigger feed-forward mechansism to preserve ABP

Stresses:

• exercise

• stranding up

• mild to moderate blood loss

Feed-forward mechanisms to preserve ABP: how can ABP drop be prevented in exercise

Inputs to medulla from:

1. cortex→ ‘decision’ to exerice

2. cerebellum→ as part of a co-ordinated motot ‘programmed’

3. muscle and join receeptors→ as direct response to movement

Feed-forward mechanisms to preserve ABP:other stresses that can cause rise in blood pressure

1. pain

2. emotions→ fear and anger

(from cortex and hypothalamus)

• forms fight or flight preparation for dealing with whatever one is worried or frightened of

• → helping the body to deal with any incipient blood loss

Integration of baroreceptors and feed-forard signals in the medulla

• many of the feed-forward mechanisms feed into the same area of the brain

  • → cardiovascular centre of the medulla

RESPONSE: medulla generates a response by…

• informed sensory input from:

  1. circulation

  2. and more strategic inputs from higher brain centres

ENABLES→ it to control ABP via 2 major efferent pathways

RESPONSE: ABP can be controlled via 2 major efferent pathways

1. sympathetic

2. parasymthatic 

divisions of the autonomic nervous system

there are also other pathways that control local blood flow→ for specific processes

• e.g sweating, salivation and digestion

RESPONSE: sympathetic outflows effect

1. act on vasculature

2. and the heart

3. also some preganglionic sympathetic fibres in the splanchhnic nerves that innervate the chromaffin cells of the adrenal medulla

RESPONSE: parasympathetic outflows effect

• heart only

RESPONSE: sympathetic efferent pathways

1. bulbospinal pathways (i.e from medulla to spinal cord)→ activate pre-ganglionic pathways

2. primarily at glutamatergic synapses 

   • between levels T1 and L3 of the spinal cord

3. these pre-ganglionic neurons synapse at nicotinic synapses to

4. postganglionic sympathetic neurons

   • found within prevertebral and paravertebral sympathetic ganglia

5. postganglionic sympathetic nerves involved in ABP run with large blood vessels to innervate:

   • muscular arteries

   • arteioles

   • veins

6. Increased sympathetic activity→

7. noradrenaline→ alpha 1 adrenoceptors

8. vasoconstriction (plus venoconstriction)

RESPONSE: effect of this sympathetic acitivsity

1. vasoconstriction→increases TPR

2. venoconstriction→ increases MSFP

3. redistribution of blood flow

   • some organs receive little significant sympathetic vasoconstrictor innervation:

     • arteries and arterioles supplying blain and heart

     • show little if any vasoconstriction during cardiovasuclar reflex responses

RESPONSE: sympathetic fibres are where

1. vasoconstrictor regions (blood vessels)

2. supply the heart

3. splanchic nerves

RESPONSE: 1. activity of sympathetic vasoconstrictor nerves

AT REST: tonically active

• resting AP frequency of 1-4Hz

  • resting tone allows inhibition of sympathetic acitivity (baroreceptor reflex)

  • to reduce ABP if needed

IN ACTIVITY →  EXTREMIS: increase activity

• 10 Hz

• reduce blood flow to some tissues to almost 0

RESPONSE: 1. why useful to have resting sympathetic tone

1. resting tone allows inhibition of sympathetic acitivity (baroreceptor reflex)

   • → to reduce ABP if needed

2. e.g spinal cord damage above T1 causes severe and rapid drop in blood pressure

   • by abolishing this resting sympathetic outflow

RESPONSE: 2. sympathetic fibres in the heart and effect

Cardiac accelerator nerves

Innervate the:

1. SA node

2. Atria 

3. Ventricles

at rest→ have a low resting frequency

EFFECT: increase both heart rate and contracility

RESPONSE: 3. activity of splanchnia nerves

1. innervate chromaffin cells in adrenal medulla

2. stimulates adrenaline release into circulation

3. acts on heart  and vasculature

   • in broadly similar manner to direct sympathetic innervation

   • via alpha 1 receptors

however…→ some tissues have different receptors

RESPONSE: 3. activity of splanchnia nerves continued (different different receptors in different tissues

1. coronary blood vessels and skeletal muscle

   • more beta2 than alpha 1 receptors

2. beta 2 receptors trigger vasodilatation

3. increasing coronary and skeletal muscle blood flow

note: noradrenaline from sympathetic nerves primarily acts on alpha 1 receptors

• allows skeletal muscle blood flow to be limited if necessary

RESPONSE: Parasympathetic afferents pathway

1. vagus nerve innervates SA node, AV noe and cardiac conducting system

2. activity slows conduction through the heart

3. lengthens cardiac cycle

4. does not influence force

RESPONSE: vagal supply to the heart shows rate parasympathetic pathway because…

• shows tonic activity

THEREFORE:

• inhibition of the vagus nerve at rest (using atropine

• significantly Accelerates the heart rate

Integration and effectiveness of circulatory control: why are there many challenges to blood pressure regulation in everyday life

• Diverse acitivties

  • running, digestion, sweating and thinking

• require blood flow to specific organs/sysms

• NEED local vasodilation 

THEREFORE: the resultant fall in TPR can be very large:

• 5 or 6 fold in whole-body intensive exercise

• YET: mean ABP stays relatively constant

Integration and effectiveness of circulatory control: Since ABP=CO x TPR→ anyfall in TPR would

• produce fall in ABP

UNLESS

• there is an adequate response

What can this adequate response be?

• small adjustments e.g by sympathetic vasoconstriction of 

  • blood vessels

  • Some tissues:→ recieve more blood that is required to meet their metabolic demands at rest

    • skeletal muscle

    • skin

    • gastrointestinal tract

BUT what about significant falls in TPR

→ demands increase in CO

requires:

1. sympathetic venoconstriction to increase MSFP

in concert with

2. Reduced vagal and increased sympathetic stimulation of the heart

3. to incrase heart rate and contracility

4. ensuring raised MSFP produces a rise in CO without necessitating an increased RAP

TOGETHER→

• increase CO

• MAINTAIN mean ABP

This lecture is about short-term control of blood pressure→ during longer term…

• circulating volume is a criticcal determinant of MSFP

• HENCE→ ABP

Other efferent pathways affectingblood flow

Congestive cardiac failure: what is the heart failing to do

In severe, end-stage heart failure:

• failture adequatley perfuse organs

• resulting in organ failture

• eventual death if untreated

In less severse heart failure:

• necessary to think more carefully about heart’s precise role

Congestive cardiac failure: Hearts basic role and basic heart failture

Role: pump blood from veins→ arteries

failure:

1. implies that artrial pressure is too high

2. arterial pressure is too low 

Congestive cardiac failure: But what does ‘too high’ Atrial pressure mean

1. Too high atrial pressure

   • should be close to 0

   • if higher→ impedes venous return

   • raise capillary pressures

   • non failing heat by Starling mechanism→ maintains RAP close to 0

Congestive cardiac failure: Too low ABP meaning

more complex because it is common to find symptoms of heart failture and hypertension in the same patient

• heart failture develops when ABP is lower than the set point and cannot be raised

Congestive cardiac failure: how does the body normally respond to lower ABP

As it does a haemorrhage:

1. increased sympathetic drive

2. venoconstriction

3. arteriolar vasoconstrction

4. renal responses (retention of fluid)

THIS CAUSES:

• raise in TPR and MSFP

Congestive cardiac failure: Effect of raising TPR and MSFP

• normally→ TPR does not influence CO (starling mechanism)

but this may not be true in failing heart:

• maintaining CO with increased TPR requires an increase in cardiac worka

similarly

• CO is normally limited by the heart

• THEREFORE

• raising MSFP will not produce a significant increase in CO

  • → INSTEAD: cause atrial pressure to rise

Congestive cardiac failure: symptoms of heart failture primarily result from

1. inability to adequately increase CO

   • reduces exercise capacity

   • may induce feelings of fatigue

2. increased atrial pressure

   • implies raised venous pressures

     • causes oedema: 

       • peripheral oedema in right-sided heart hailture

       • pulmonary oedema in left-sided hart failture

Congestive cardiac failure: Need to understand physiology of heart failture to understand treatment

1. To improve cardiac output: (little can be done)

   • valve repair, pacing, coronary bypass

   • can treat failture resulting from valve disease, rhythm disorders and severse angiana (respectively)

2. To inhibit responses to low blood pressure 

   • angiotensin converting enzyme (ACE inhibitors)

   • diurentics

     • → produce significant symptomatic relief

       • lower MASFP and TPR

       • AS A RESULT: reduces the symptoms:

       • reduces oedmea nad reduce cardiac oxygen demand

         • perhaps even without decreasing CO!