cvs bims revision session 2014

8/13/2019 CVS BIMS Revision Session 2014

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Electrical Activity of the Heart

The Cardiac Cycle

Regulation of Cardiac Output

Anti-Arrhythmic Drugs

Heart Failure


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The heart is formed out of two

types of muscle cells

o Cardiac Myocytes

o

Cells of the cardiacpacemaker-conduction

system

The cells of the pacemaker-

conduction system generate an

electrical signal

Propagated signal elicits

myocytes contraction


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Cardiac myocytes arranged

in an end-end fashion

separated by intercalated

discs

At rest, there is high PK+ &low PNa+, PCa2 +

Resting potential at rest is

stable

Depolarisation threshold of

-65mVs

Depolarisation caused by

influx of Na+and Ca2 +

Unique plateau phase -

inward current of Ca2 +

Results in long refractory

periods

Repolarisation occurs via

efflux of K

+


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Initial resting potential of -70 mVs

Electrically unstableautomatically

generates repetitive rhythmic action

potentials

Due to unique recycling changes in

the PK+, PNa2+, PCa2 +

Threshold potential is -50 mVs

Depolarisation is facilitated by influx

of Na2+and Ca2 +

Repolarisation is facilitated by K+

efflux

The SAN has intrinsic rate

of 100 bpm; AVN 40 bpm

AVN adds 100 msec

delay


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ParasympatheticVagus (CN X)

o Innervates SAN & AVN predominantly

o Decrease HR by decreasing SAN firing frequency and increasing AVN

delay

Sympathetic

o

SAN, AVN and ventricular muscle

o Increase HR by increasing SAN firing frequency and decreasing AVN

delay

o Increase ventricular contractility


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Normal heart beat70 bpm

Cycle duration850 msecs; two thirds in diastole

Relative pressure gradient between chambers and their outlets

determine position of the valves

1st heart sound = AV valve closure

2nd heart sound = Aortic & pulmonary valve closure

EDV = volume in left ventricle at the opening of the aortic valve

ESV = volume at closure of aortic valve


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CO is total volume of blood ejected from the left ventricle into the

systemic circulation per unit of time

CO = HR x SV ; CO = ABP/TPR

SV is dependent on 2 opposing factors:o Energy of myocyte contraction

o TPR(After load)

Energy of myocyte contraction is in turn dependent on two

processes:

o Myocyte contractility

o EDV (Pre-load)


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Innate strength with which a myocyte contracts from a given initial

stretch

Increased by nervous, hormonal and chemical influences

Is dependent on Ca2+induced Ca2+release from the SR

1. Ca2+binds to Troponin on the Tropomyosin

2. Frees the Myosin binding sites on Actin filament

3. Leads to the formation of cross links

4. ATP hydrolysis facilitates breakage of cross links which pulls the

filament towards the centre of the sarcomere


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Through his experiments, Starling found that if other factors such as TPR

and ABP are kept constant, an increased EDV leads to an increased SV

Increased EDV due to increased venous return leads to:

1. Increased EDP

2. Greater distension and stretch of ventricular myocytesmore

filament overlap

3. Ventricles develop greater contractile energy

4. Larger SV

The force of ventricular contraction depends on the length of

the ventricular muscle fibres during diastole (EDV)


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HR - >180 bpm

Atrial Contractionat high rates, EDV is more atrial dependent

TPRreduce stroke volume and therefore increase ESV

CVPlargest influence on EDV of the right heart

o Increased blood volume

o Increased activity of skeletal muscle pump

o Increased activity of the respiratory pump

o Increased venous tone

o Posture


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Clinical syndrome arising from an inability of the heart to produce

a cardiac output that is sufficient for the metabolic demands of

the body

Caused either by intrinsic diseases of the myocardium (i.e.

cardiomyopathies) or by chronic overloading of the myocardium

(i.e. valvular disease/hypertension)

Symptoms include dyspnoea, PND, orthopnea and peripheral

oedema

Causes a rightward shift in Starling curveSV is reduced at normal

filling pressures


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HF leads to the activation of compensatory neuro-hormonal

mechanisms

Whilst this initially compensates for the reduced CO, chronic activation

leads to increases in the pre & after load, thus increasing cardiac work


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Aims of treatment are two fold:

o Block the pathways that cause further deterioration

o Improve symptoms

Drugs used:

o Diuretics

o ACE Inhibitors

o AT Receptor Antagonists

o Aldosterone Receptor Antagonists

o Cardiac glycosides

o Vasodilators

o - blockers


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Elastic Arteries

Arterioles

Capillaries

Venous Vessels

Pulmonary Circulation

Coronary Circulation


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ABP = CO x TPR; MABP = DP

+ 1/3(PP)

Elastic arteries are the

primary site where ABP is

determined

Coverts the intermittent flow

into continuous flow

Can distend under pressure

to accommodate blood

flow during systole and

maintain blood pressure

during diastole by recoiling

This is due to the distinct

biomechanical properties conferred by

the tunica media


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During systole, opening of

aortic valve results in the

ejection of the SV into the

aorta

Approximately 20% of the

ejected blood flows straight

through the vessels

80% distends the aorta and

this stretching is stored as

potential energy

During diastole, elastin

recoil returns this energy to

the blood to maintain flow

This creates a travelling

pressure wave


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The composition of the elastic arteries is prone to change with age

There is loss of elasticity of the tunica media leading to a decrease

in compliance

This increased rigidity leads to an increase in the SBP

The decreased recoil results in a decrease in DBP

Leads to age dependent increase in PP


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Blood is a homogenous fluid

Flow is in a laminar pattern

Each successive laminae from the edge to the centre is of a higher

velocity

Maximum velocity is at the centre of the vessel which is occupied by

RBCs

Laminar blood flow is silent


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Blood may also be turbulent

Here the currents swirl in random

moving patterns

Dissipates pressure energy as heat

and sound

Occurs during high blood velocities,

pregnancy, hyperthyroidism and at

sites of atheroma formation

Turbulent flow leads to bruit


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SBP

Increased SV

Increased Contractility

High CO states

DBP

Increased TPR

Increases in HR


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Main site of resistance in the vascular system and therefore the main

component of the TPR

Through constriction and dilatation, arterioles can increase or

decrease ABP

As such they are the main regulators of ABP

This is due to the higher density of smooth muscle and sympathetic

receptors allowing arterioles to exhibit wider control of changes in the

diameter in reaction to local influences


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Endothelium derived substances

o NO, PG2

Myogenic tone

o An increase in BP causes vasoconstriction allowing flow to remain the

same

Metabolic vasodilators

o Dilatation caused by products of metabolism

Nerve fibres

o Sympathetic supply to arterioles evoke constriction. Parasympathetic

supply to arterioles of the brain, heart and genitalia causes dilatation

Hormones

o Circulating noradrenaline causes constriction whilst adrenaline causes

dilatation in the skeletal muscle. ADH and AII cause constriction


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Relative constancy of flow

despite changes in ABP

over a certain range

Thought to occur through

myogenic tone

Independent of neuro-

hormonal influences


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The delivery of metabolic substrate to tissues occurs across the

capillary wall

It is also the site of fluid exchange between the plasma and the

interstitial compartments

Capillaries do not have any smooth musclethey are of a fixedresistance

Blood velocity is lowest in the capillaries which in conjunction with

the increased TSA make the region ideal for exchange

Exchange can occur through two mechanisms:

o Diffusion

o Filtration


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The rate of diffusion is dependent on:

1. The permeability of the capillary

2. The concentration gradients across the capillary walls

3. The surface area available for diffusion

Mathematically= Px (C1-C2)x A


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Passive movement of fluids across the capillary wall

The net rate/direction of fluid across any given segment of the

capillary wall depends on the net filtration pressure

Net filtration pressure = hydrostatic pressure gradientthe oncotic

pressure gradient

o CHP = 35 mmHg; decreases to 15 mmHg at venous end

o THP = 0 mmHg

o COP = 25 mmHg

o TOP = 2-3 mmHg


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Arteriolar constrictiono Increase arteriolar resistance and reduce downstream flow and

pressure

o This will cause momentary cessation of blood flow thus reducing

capillary surface area available for diffusion and decrease the CHP

o Lead to decreased filtration

Arteriolar dilatation

o Decrease resistance and increase downstream flow and pressure

o This will increase capillary recruitment and CHP

o Lead to increased filtration

o This can lead to oedema if the lymphatic system cant cope


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Increased CHPFluid out > Fluid in

Decreased CHP

Fluid out < Fluid in


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Changes in capillary or tissue oncotic pressure can also affect the netfiltration process

An increase in COP will lead to greater reabsorption of fluid

This will increase blood volume and can occur due to water loss,

diarrhoea, vomiting and profuse sweating

Conversely a decrease in COP will lead to greater filtration

This will lead to oedema and can be due to decreased synthesis of

plasma proteins or increased loss of plasma proteins

Whilst the TOP is relatively small, it may increase when the vascular

permeability increases during inflammation

This will decrease the oncotic pressure gradient and favour filtration


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Increased COPFluid out < Fluid in

Decreased COPFluid out > Fluid in(Increased TOP)


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Compared to arteries and

arterioles, veins have:

o Greater compliance

o Larger proportion of theblood volume

o Larger diameter

o Larger cross sectional area

o Lower resistance

o More branched

o Have valves


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Compliance is a feature of collagen

found in the walls of the vein

In a low volume supine state, the

collagen is pleated

As volume increases, the collagenunfolds allowing for a more rounded

shape

Veins also have smooth muscle in the

tunica media which can contractupon sympathetic stimulation

This limits the distension of a vein and

therefore makes them less compliant


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1. Veins are one of the determinants of filtration of fluid across

capillaries

2. Veins act as a major reservoir of blood which can be mobilised

depending on the bodys need

3. Veins are an important determinant of the EDV of the right heart


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The pressure in veins depends on how much volume they contain

and the state of their smooth muscle

Passive influences:

o Blood volume

o Posture

o Skeletal muscle pump

o Respiratory pump

Active influences:

o Sympathetic NA nerve activity


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Low pressure

Loss of pressure from

arteries to capillaries is

more gradual

MPABP is approximately

12-14 mmHg

Low resistance

Larger diameter

Shorter in length

High compliance


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Passive influences:

o Blood volume

o Posture

Active influences:

o Sympathetic nerve activity

o Hypoxia

o Chemical mediators such as histamine and bradykinin


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Provides oxygen at a high rate to

keep pace with cardiac demand

Two main arteries : RCA & LCA

Receives 3-4% of the total CO whichequates to 80-90 mls of oxygen per

min per 100 g of muscle

Large percentage of oxygen

extraction by the myocardium70% -

80%


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The branches of the coronary artery (particularly LCA) within the

myocardium are exerted to compression during each ventricular

systole

During systole, LV pressure rises to 120 mmHg, pushing blood through

the aorta and coronary vessels at the same pressure

However as coronary vessels enter the depths of the myocardium,

they get smaller and increase in resistance

The pressure here reduces to 80 mmHg

As such during systole, there is occlusion of the myocardial coronary

vessels due to mechanical compression from the LV


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During diastole, ventricular relaxation results in a decrease in LV

pressure to about 8 mmHg

The recoil of the elastic arteries maintains an initial coronary pressure

of 80 mmHg

Again due to the increased resistance, the coronary vessels of theinner myocardium have a minimal pressure of 40 mmHg

However since this is greater than the LV pressure, there is no

occlusion of the vessels

Note: The right ventricular pressures are always lower than the

systolic and diastolic blood pressures and as such there is no

occlusion of blood flow. However overall average flow is the RCA is

lower.


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Myocardialhypoxia

SystemicHypoxia

Increasedmyocardialmetabolism

Decreasedcoronary flow

Activates 5

nucleotidase


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5 nucleotidase catalyses the formation of adenosine from AMP.

Adenosine accumulates in the interstitial fluid and induces coronary

vasodilatation

This mechanism is occurring continuously even at rest

However if cardiac work increases and an individual doesnt have a

large capacity for further vasodilatation, angina develops

Therefore it can be seen that the local factors of mechanical

compression and chemical factors involving adenosine are the most

important influences on coronary flow


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The coronary vessels also receive sympathetic and parasympathetic

nerve supply

Increased sympathetic NA activity causes vasoconstriction

Increased Parasympathetic cholinergic activity causes

vasodilatation

However in both these effects tend to be overcome by the effects

on CW and subsequent adenosine release


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Usually caused by coronary artery disease secondary to

atherosclerosis

Treatment:

o Vasodilators

o blockers

o Diuretics

o PCTA or CABG

Variant angina is pain associated with a constant level of cardiac

work. This occurs because of coronary artery spasm possibly due to

selected activation of sympathetic fibres leading to vasoconstriction


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Baroreceptor reflex

Atrial Volume reflex

Orthostasis

Cardio-Respiratory Interactions

Exercise reflex

The Alert-Defence Response


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The baroreceptor reflex is thepredominant homeostatic regulator of

ABP on a beat to beat basis

The baroreceptors are stretch receptors

that are located in two specific locations:

o The carotid sinus

o The aortic arch

They respond to changes in the ABP via

the stretch it evokes on the arterial wall

Stimulation brings about reflex

mechanisms which return ABP to the

normal value


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Baroreceptors arecontinually active and

monitor ABP via the stretch it

causes

Afferent nerve activity

reflects the changes in the

pressure exerted within the

artery

Receptors are not only

sensitive to the amount of

stretch, but also the rate of

change


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Afferent fibres via CN IX and X enter the NTSthese are excitatory

neurones

NTS sends inhibitory neurones to the pre-motor sympathetic neurones

in the brain

Also sends neurones to the pre-optic hypothalamus which in turn also

send inhibitory signals to the pre-motor sympathetic neurones

The NTS also sends excitatory neurones to the NA

This increases vagal tone to the heart

A final branch is sent to the supra-optic and paraventricular nuclei

which inhibits ADH release from the posterior pituitary


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Volume receptors are located in the right atrium

They are stretch receptors that respond to increased venous

return

Send afferents via CN X to the NTS

Increased stimulation brings about reflex changes which return

atrial volume to normal

Reflex has two components:

o Transient increase in sympathetic supply to the heart

o Large decrease in sympathetic activity to the kidneys and

the pituitary gland


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Bainbridge reflex NTS increases sympathetic

stimulation of the heart

Increases the HR

Reduces the time the heart

has to fill and prevents over-

stretching of the atria

Initial protective function

Main reflex

NTS decreases sympathetic

supply to the kidneys leading

to vasodilatation

This reduces activation of the

RAAS

Furthermore NTS inhibits

pituitary secretion of ADH

This reduces fluid retentionOverall:

Decrease venous return

Decrease atrial filling


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When supine, ABP is uniformly distributed throughout the body at

approximately 95 mmHg

At the level of the heart it is 100 mmHg

Similarly venous pressure is uniformly distributed through the body at 5

mmHg

At the level of the heart it is 3 mmHg

100 mmHg

3 mmHg

95 mmHg

5 mmHg

95 mmHg

5 mmHg


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Upon standing, there is a redistribution of blood towards the lower

extremities

55 mmHg

-35 mmHg

100 mmHg1 mmHg

195 mmHg105 mmHg


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Respiratory influences on the heart can take the form of mechanicaland neural influences

The mechanical influence involves the respiratory pump

The neural interaction causes an increase in HR during inspiration

This is physiologically normal and known as RSA

Increased HR

Expiration

Inspiration

Decreased HR


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Mechanism 1

Mechanism 2


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Peripheral chemoreceptors are responsible for the homeostatic

regulation of primarily Pa02

These receptors are located in the carotid and aortic bodies, in

close proximity to the carotid and aortic baroreceptors

Reflexes from the peripheral chemoreceptors include:

o Primary cardiovascular reflex

o Secondary cardiovascular response


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When respiration can increase, systemic hypoxia evokes

tachycardia in addition to vasoconstriction

Increased respiration leads to modulation of the primary

cardiovascular reflex

This occurs via:

o Activation of the pulmonary stretch receptor reflex

o Direct inhibition of the NA from the inspiratory centres of the brain


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Reflex elicited by stimulation of the trigeminal afferents in the

face/nose

Trigeminal afferents travel to the NTS which sends inhibitory neurones

to the inspiratory centre

This result in total inhibition of the central inspiratory drive

This leads to expiratory apnoea

There is increased NA activity leading to bradycardia

In addition the increased sympathetic tone to the vessels leads tovasoconstriction


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Two types of exercise:o Static

o Dynamic

Both forms of exercise evoke some CV changes:

o HR increases

o CO increases

o Blood flow increases

The cardiovascular response to exercise involves the exercise reflex

superimposed upon the local responses to metabolic activity in the

muscles and the heart


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During static exercise, the heart rate increases in proportional to the

amount of exercise done

During dynamic exercise, again the HR increases in proportional to

the amount of exercise done

However the increase is usually greater compared to static exercise


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During static exercise, blood pressure increases in proportion to the

level of exercise

This is due to the compressive impairment of muscle perfusion which

increases the activity of the muscle metaboreceptors

This leads to a strong exercise pressor reflex which causes

vasoconstriction

During dynamic exercise, the increase in CO is nearly totally

balanced by a fall in TPR and therefore mABP changes very little

SBP increases due to the increased HR and CO

However DBP does not increase and may even fall


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During static exercise, there is an overall increase in blood flow

The greatest increase in blood flow occurs during relaxation

This is because contracting muscle exerts a mechanical occlusive

force on the blood vessels, thus increasing the resistance

During dynamic exercise, here is also a general increase in blood

flow

The increase occurs regardless of contraction/ relaxation

This is because dynamic exercise involves cycles of

contraction/relaxation and there is no great occlusive effect on the

vessels


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Reflex is elicited by metaboreceptors located in the muscle

These are free nerve endings in the interstitial space between

muscle fibres

Upon stimulation by metabolites, they send afferents to the

hypothalamic locomotor region

Via efferent pathways, the reflex response involves:

Increase in respiration

Increase in HR

Increase in contractility


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The exercise reflex also increases sympathetic NA supply to theskeletal muscles, GIT and kidneys

This mediates vasoconstriction

However working muscles overcome this neural influence via local

metabolic hyperaemia


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Negligible role during mild to moderate exercise

They respond predominantly to changes in PaO2and PaCO2

Central chemoreceptors are responsible for responding to changes

in PaCO2

Peripheral chemoreceptors are responsible for regulating PaO2

However the peripheral chemoreceptors may also respond to

arterial pH during severe exercise which induces acidosis


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The magnitude of the response is dependent of the strength of the

stimulus

The alerting response is common to mammalian species

The response can show habituation or sensitisation

It can be conditioned

Activation of the alert response suppresses the baroreceptor reflex


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Located primarily in the hypothalamus

However there are multiple connections from the hypothalamus to

other important areas:

o To the amygdaloid defence area

o

Up past the fornix to the stria terminaliso Stria terminalis in turn sends connections back to the amygdaloid

defence area

This forms a circuit between the 3 regions which positively reinforces

the pathway meaning that the response can often outlast the

stimulus


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Connection toamygdaloiddefence area

Connection to striaterminalis

Connection back toamygdaloiddefence area


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The prefrontal cortex provides either positive or negative modulation

via the main integrating areas

From the defence area, connections leave the brain via the ventral

medulla from where synapses to the efferent nerves are formed


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In type A personalities, continuous or repeated exposure to stressful

stimuli may lead to strong alerting responses

Repeated activation and subsequent suppression of the baroreceptor

reflex may be associated with the development of essential

hypertension

This is supported by the link between essential hypertension, stress

levels and type A personalities

Furthermore there is also the acute dangers of an uncontrolled rise in

ABP in patients with cerebrovascular disease, coronary artery disease

and aortic aneurisms


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GIT and skeletal muscle vasoconstriction

The skin if in thermal balance will undergo vasoconstriction

If there is a large change in ABP, there will be renal

vasoconstriction

This will lead to further constriction via activation of the RAAS

The cerebral and coronary circulation is not affected as they

lack a large sympathetic supply


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cvs bims revision session 2014

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