Summary CVS

8/2/2019 Summary CVS

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CARDIOVASCULAR PHYSIOLOGY

MED2031Cardiovascular System Overview

A/Prof Igor WendtRoom: F130, Department of Physiology

Phone: 9905 2511Email: [email protected]

Textbook References: Davies, et al. Human Anatomy & Physiology, Section 6Saladin, Anatomy & Physiology, Chapters19 & 20

Why do we have a circulatory system?

TRANSPORT FUNCTION

1. Supply nutrients + O2 to organs and tissuesRemove CO2 + waste products

2. Co-ordinate body functions- transport chemical messengers (e.g., hormones)

3. Defence mechanism- transport antibodies and white blood cells to sites of injury/infection

4. Heat transfer (especially by circulation to skin)

COMPONENTS OF THE CIRCULATORY SYSTEM

Fluid in the BLOODsystem

Tubes throughwhich the blood BLOOD VESSELSflows

CARDIOVASCULARSYSTEM

Pump to produce HEARTthe flow

BLOOD

Specialized cells suspended in a fluid

Plasma: 93% water with dissolved substancese.g. electrolytes, proteins, nutrients, wastes, hormones

dissolved gases

Cells: 1) Red blood cells ~ 5 billion per ml (> 99% of all blood cells)- transport oxygen


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2) White blood cells (leucocytes)

- immune system

3) Platelets - crucial role in blood clotting

HAEMATOCRIT = % volume of blood occupied by cells

Centrifuge

Haematocrit 45% in men

42% in women

TOTAL BLOOD VOLUME

In mammals blood volume equals approximately 8% of body weight.

e.g. 70 kg person

Blood volume = 70 kg x 0.08 = 5.6 kg = 5.6 litres

CARDIOVASCULAR SYSTEM

HEART PUMP

BLOOD VESSELS Plumbing

Two functional halves:

Left Heart and systemic circulation (operates at high pressure)

Right Heart and pulmonary circulation (operates at low pressure)

The system is sealed.

Blood flows in a continuous loop through the cardiovascular system.

Overall flow through the systemic and pulmonary circulations is IN SERIES.

In the pulmonary circulation ALL the blood goes through the lungs.

55% plasma

45% red blood cells


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In the systemic circulation it is shared between different organs and tissues.

i.e. flow is in PARALLEL through different organs.

**** See, DAVIES et al., Figure 6.1.1 ****SALADIN, Figures 19.1 & 20.1

COMPONENTS OF THE CARDIOVASCULAR SYSTEM

HEART (Atria) - Receive blood returning to the heart from the veins.

HEART (Ventricles) - Chambers whose contraction generates the pressure to drive theflow of blood

ARTERIES --

-

Have low resistance to flow.Conduct blood to organs and tissues with little loss of pressure.Act as pressure reservoirs.

ARTERIOLES --

Smallest arteries branch into arterioles.Arterioles are the flow regulating system.Control resistance to flow and, therefore, the distribution of flowbetween the different organs and tissues.

CAPILLARIES - Site where substances are exchanged between the blood andcells of the body.

VENULES - Collect blood from capillaries.

VEINS - Return blood to the heart.Low resistance.Volume Reservoir Function

Where is the blood?

Under resting conditions

~ 12% is in the pulmonary circulation

~ 9% is in the heart itself

~ 11% is in the systemic arteries

~ 7% is in the arterioles and capillaries

~ 61% is in the systemic veins and venules


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FLOW OF FLUID THROUGH TUBES

Difference in pressure causes flow

Flow is always from region of high pressure to region of lower pressure

P1 P2

P = 0 mmHgNo flow

100 mmHg 100 mmHg

P1 P2

P = 50 mmHgFlow = 5 l/min

100 mmHg 50 mmHg

P1 P2

P = 50 mmHgFlow = 5 l/min

200 mmHg 150 mmHg (same as above)

It is the DIFFERENCE in pressure that is important, not the absolute pressure.

Flow is proportional to the pressure difference (F P)

Directly proportional if flow is laminar.

Laminar flow

- smooth, silent.

Flow in blood vessels is normally laminar.

Turbulent flow

swirling, noisy.

Occurs where there is obstruction to flow.

**** See, DAVIES et al., pp. 509-510 ****SALADIN, Figures 19.1 & 20.1


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RESISTANCE TO FLOW

Flow is determined not only by P but also by the resistance to flow.

3 factors determine resistance

1) Viscosity of fluid (

viscosity

resistance)

2) Length of tube (R length of tube)

3) Radius of tube (R 1

4r)

Viscosity : blood is thicker than water

At normal haematocrit ~ 45% viscosity of blood 3 x that of water

At haematocrit ~ 60% viscosity of blood 7 x that of water

At haematocrit ~ 25% viscosity of blood 2 x that of water

**** See, DAVIES et al., Figure 6.1.11****

Haematocrit is usually maintained relatively constant

Can be abnormally low in anaemia or abnormally high in polycythemia or severe dehydration.

BLOOD DOPING as an example.

Factors Affecting Resistance to Flow

Viscosity - normally relatively constant

Length of tube - cannot change in body

Radius of tube - can and does change (constriction or dilation of blood vessels)

Main factor controlling resistance to blood flow in the body is the diameter (radius) ofthe blood vessels [primarily the arterioles].

Diameter of blood vessels is controlled by smooth muscle in the blood vessel walls

Orientated circularly

Contraction of the smooth muscle causes narrowing of diameter (constriction)

Relaxation of the smooth muscle causes widening of diameter (dilation)

Basic flow equation F =P

R


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BLOOD DOPING

Attempt to enhance athletic performance by increasing O2 carrying capacity of blood.

Blood withdrawn at intervals several weeks prior to event

- red blood cells separated and frozen

- plasma reinfused

Normal haematocrit restored quickly by body producing new RBCs.

Frozen RBCs thawed and re-injected shortly before event.

Raises haematocrit up to ~ 60-65%

Benefit to performance is not as great as might be expected because the increased viscosityof the blood increases resistance and reduces flow to all organs, including the skeletalmuscles and the heart. (Viscosity is increased by a factor of 2 or more.)

i.e. benefit of increased O2 carrying capacity is largely offset by decreased blood flow.

Banned by most sporting bodies.

Can only be detected by a blood test. Urine tests can not reveal it.

More recently synthetic erythropoietin (EPO) has been used to boost RBC count.


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Aortic and Pulmonary Valves (semilunar valves)

Allow flow from ventricle into arteries (aorta or pulmonary artery)

but prevent backflow from arteries to ventricles

**** See, SALADIN, Figures 19.6 to 19.9 ****

The valves are passive structures. They simply open or close depending on the relativepressures on either side of them.

Papillary muscles help to anchor the atrio-ventricular valves during ventricular contraction.

VALVULAR HEART DISEASE

1. Valve opening is narrowed (stenosis) restricts flow

2. Valve leaky allows backflow of blood (insufficiency)

Valve problems are often detected as heart murmurs

Flow through impaired valve is turbulent - noisy

FIBROUS SKELETON OF HEART

4 Rings of dense connective tissue

Ventricles are attached below and atria, aorta and pulmonary artery are attached above.

The heart valves are attached to these rings.

**** See, SALADIN, Figure 19.7 ****

Important consequences for excitation of the heart because they electrically isolate atria fromventricles (see lecture notes on Electrical Acrivity of the Heart)

CARDIAC MUSCLE Unique to the heart.

Similarities to Skeletal Muscle

Thick and thin filaments arranged into sarcomeres.

Sliding filament mechanism of contraction

Cross-bridge cycle

Contraction on-off switch is Ca2+ binding to troponin

Differences from Skeletal Muscle

Cardiac muscle cells are smaller

Cardiac cells connect to each other (not to tendons)

via specialised junctions called intercalated disks

mechanical connection (desmosomes)

electrical connection (gap junctions)

allow action potentials to spread from cell to cell



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No direct nerve control

Each cardiac cell does not receive a direct nerve input

Duration of action potential is very long

about 200 msec compared with 2 msec in skeletal muscle

almost as long as the duration of the contraction

prevents tetanic contractions

**** See, SALADIN, Figure 19.14 ****DAVIES et al. Figure 6.2.14

Mechanism of Ca2+ release (see Excitation-Contraction Coupling)

This is a subtle difference but very important in the control of the strength of contractionof the heart muscle.

A point of interestIn skeletal muscle the strength of contraction is graded mainly by:

1. Recruitment of motor units, and

2. Frequency of excitation tetanic contractions

The heart can not use either of these mechanisms.

In cardiac muscle the strength of contraction is graded by:

1. Changes in muscle length, and

2. Changes in the amount of Ca2+ released

EXCITATION-CONTRACTION COUPLING

Action potential leads to increase in intracellular Ca2+ concentration

Both the sarcoplasmic reticulum and the extracellular Ca2+ pools are involved

Ca2+ influx from the extracellular space is essential for contraction

If no extracellular Ca2+, or if Ca2+ influx is blocked - no contraction

Ca2+ influx triggers release of Ca2+ from the SR ("Ca2+-induced Ca2+ release")

also promotes filling of SR


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EXCITATION-CONTRACTION COUPLING IN CARDIAC MUSCLE

**** See DAVIES et al. Figure 6.2.13 ****

Ca+

bindsto troponin

Cross-bridge cycle startsContraction

Intracellular Ca+

concentration rises

Ca2+ enters fromextracellular space

(Ca2+

influx)

Voltage-dependentCa

2+channels in

membrane open

Action PotentialDepolarisation of

membrane and T-tubules

Triggers release of more Ca2+

from the sarcoplasmic reticulum

Ca2+

-induced Ca2+

release


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GRADING THE STRENGTH OF CARDIAC MUSCLE CONTRACTION

Two mechanisms 1) Changes in muscle cell length

2) Changes in calcium release (changes in contractility)

Changes in muscle cell length

Cardiac muscle is striated (sarcomere structure) and contraction is via the sliding filamentmechanism as in skeletal muscle.

It, therefore, has a similar LENGTH FORCE RELATION

Force of contraction varies with muscle cell length.

Degree of overlap of the thick and thin filaments changes

**** For revision see, SALADIN, Figure 12.12 ****DAVIES et al. Figure 2.2.7

In the normal heart the cardiac muscle cells are at relatively short lengths

o Well down on the left side of their length force relation

In the intact heart the length of the cardiac muscle cells changes with changes in the filling ofthe heart with blood.

o Increased filling stretches the cardiac muscle cells

o They contract with greater force as a result (move up the ascending part of thelength force relation)

Changes in calcium release

In a normally contracting heart not enough calcium is released with each action potentialto fully switch on all the cross-bridges.

As a result the contraction is not of maximum possible strength.

If more calcium is released the contraction will be stronger and if less calcium is released thecontraction will be weaker.

The amount of calcium released into the cytoplasm depends on.1. How much calcium is stored in the sarcoplasmic reticulum i(i.e., how full it is).

and

2. How much calcium enters the cell through the voltage-operated membrane calciumchannels (i.e., how trigger influx there is).

The amount of calcium released by the calcium-induced calcium release mechanismdepends on these two factors


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NOURISHING THE HEART MUSCLE

The heart needs a continual supply of energy (ATP) to fuel its continuous rhythmic activity.

It relies on oxidative metabolism (mitochondria) to produce this ATP

The heart is a highly oxygen-dependent organ and is,therefore, crucially dependent on

an adequate blood supply.

Blood supply to the heart muscle is provided by the coronary circulation.


Impairment of the coronary blood supply (coronary artery disease or blockage) has seriousand life-threatening consequences (angina, heart attack).

Impaired blood flow limits ATP production

Contractile capacity diminishes

If the blockage is severe cells downstream are deprived of blood supply

Contraction fails

Metabolic wastes are not washed away

Cell integrity is eventually compromised

Cells die (infarct)


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MED2031 Cardiovascular Physiology Igor Wendt, Lecture 3

ELECTRICAL ACTIVITY OF THE HEART

PACEMAKER CELLS

Generate action potentials spontaneously

Resting membrane potential is not stable

drifts slowly toward threshold for action potential

Slow depolarisation (pacemaker potential)

Due to: gradual closure of K+ channels

together with inward leak of Na+ and Ca2+

**** See, DAVIES et al., Figure 6.2.4 ****SALADIN, Figures 19.13

Cardiac cells are electrically coupled to one another (action potentials spread from cell tocell).

Pacemaker with the fastest rhythm will drive the whole heart under normal circumstances.

Cardiac cells play Follow the Leader

ORIGIN OF THE HEART BEAT

Sino-atrial node is the normal pacemaker of the heart.

(small group of cells in the right atrium near entry of the superior vena cava)

SA node cells have the fastest inherent rhythm

about 100 action potentials per minute

but this can be altered by the Autonomic Nervous System)

SPREAD OF EXCITATION

Involves specialised conducting tissues

modified cardiac muscle cells

conduct action potentials faster than normal cardiac muscle cells


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Excitation originates in Sino-atrial node (Primary pacemaker)

Atrioventricular node (Secondary pacemaker)

Bundle of His

Apex of ventricle

Purkinje fibres (Tertiary pacemaker)

Rest of ventricle

**** See, DAVIES et al., Figure 6.2.3 ****SALADIN, Figures 19.12

Features to note

1) Fibrous skeleton of the heart electrically isolates the atria from the ventricles.

AV node and Bundle of His are the only electrical connection between theatria and ventricles.

2) Propagation through the AV node is slow.

introduces a delay, allowing contraction of the atria to finish before theventricles contract.

3) Propagation through the Purkinje fibres is faster than through the normal ventricular cardiaccells.

action potentials reaches apex of the heart ahead of higher regions of the ventricles.

ventricular contraction commences at the apex

Conducting system allows co-ordinated spread of excitation to ensure co-ordinatedcontraction and efficient pumping.

Disorders of excitation (Arhythmias)

Atrial flutter

AV node block - partial- complete

Block in conducting systemRight or Left Bundle Branch block

Ectopic beats (extra beats)


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Ventricular Fibrillation (disorganised regional contraction - no effective pumping)

Primary cause of most cases of cardiac arrest.

Defibrillation as an emergency measure (strong electric discharge through the chestwall).

ACTION POTENTIALS IN DIFFERENT REGIONS OF THE HEART

The action potentials in the different regions of the heart are different in their time courses.

**** See, DAVIES et al., Figure 6.2.1 ****

This is because of differences in the ionic currents that underlie them.

The SA node Action Potential

The resting membrane potential is not stable (see above)

The upstroke of the action potential is due to inward calcium movement (through voltage-activated calcium chanels).

Repolarisation is due to outward potassium movement.

The Ventricular Action Potential

The resting membrane potential in ventricular (and atrial) cardiac muscle cells is stable (close tothe potassium equilibrium potential).

Ventricular cardiac muscle cells do not normally exhibit any spontaneous (pacemaker) electricalactivity.

The ventricular action potential has three distinct components

Upstroke (depolarisation) due to fast inward Na+ current

Plateau due to slow inward Ca2+ current

Repolarisation due to outward K+ current


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REGULATION OF HEART RATE

SA node is the normal pacemaker

Has intrinsic rhythm of100/min

Receives nerve input from the autonomic nervous system

Sympathetic stimulation increases rhythm

Parasympathetic stimulation decreases rhythm

Resting heart rate is normally 70/min because of continual parasympathetic input at rest(slows heart rate from 100/min to 70/min)

Heart rate is increased by

1) reducing parasympathetic input to SA node

2) increasing sympathetic input to SA node

Sympathetic stimulation of SA node

noradrenaline (adrenaline)

increases rate of closure of K+ channelsand inward Na+ and Ca2+ leak

faster rate of slow depolarisation

threshold reached earlier

heart rate increases

Parasympathetic stimulation of SA node

acetylcholine (vagus nerve)

hyperpolarises SA node cells

decreases rate of closure of K+ channelsand inward Na+ and Ca2+ leak

slower rate of slow depolarisation

takes longer to reach threshold

heart rate decreases

**** See, DAVIES et al., Figure 6.2.20 ****

A point of interest regarding heart rate

Heart rate is inversely proportional to body size (mammals)

Human 70/min

Rat 300/min

Etruscan shrew 1000/min

Blue whale 10/min

C0NTROL OF HEART RATE

Heart rate is controlled by the autonomic nervous system acting on pacemaker cells of the SAnode.


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1. Decreased by parasympathetic stimulation

2. Increased by sympathetic stimulation and circulating adrenaline

Other factors can influence heart rate (e.g., ionic imbalances in extracellular fluid - especially K+concentration, body temperature) but these dont play a role in normal control of heart rate.

There is an upper limit to heart rate.

cant go above about 200/min

pumping becomes inefficient because there is not enough time between contractions tofill the ventricles with blood

Resting heart rate in a normal individual is 70/min

In a highly trained athlete it may be as low as 40/min

Gives greater potential (or reserve) for increase.

If resting HR is 70/min, going to 200/min is an 3x increase

If resting HR is 40/min, going to 200/min is a 5x increase

Another advantage of a low resting heart rate is that it is energetically less costly (i.e.,the heart uses less oxygen at a lower heart rate).

A point of interest

Maximum heart rate decreases with age. Rates close to 200/min can be achieved by healthyyoung adults but in older adults maximum heart rates (e.g., during intense exercise) are less.

As an approximation: Maximum HR 220 age


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EVENTS IN THE CARDIAC CYCLE

The heart alternately contracts and relaxes in a rhythmic and coordinated fashion to achieveeffective pumping of blood.

This involves a closely integrated sequence of events in what is termed the cardiac cycle.

Definitions

Systole = period of contraction

Diastole = period between contractions

Remember

1) Blood always flows from a region of high pressure to lower pressure.

2) Heart valves are either open or shut depending on the relative pressures on either side

of the valve.

5 Phases of the cardiac cycle

1. Passive filling of ventricles

2. Atrial contraction

3. Isovolumetric ventricular contraction

4. Ventricular ejection

5. Isovolumetric ventricular relaxation

In understanding the cardiac cycle we need to appreciate the importance of

A) the control of the directional flow of blood through the hearts chambers by the heartvalves, and

B) the coordination of the spread of excitation through the heart by the conducting system.

HEART VALVES

Atrioventricular Valves -Mitral valve (between left atrium and ventricle)

-tricuspid valve (between right atrium and ventricle)

Allow flow from atria into ventricles

but prevent flow from ventricles back into atria

Aortic and Pulmonary Valves (semilunar valves)

Allow flow from ventricle into arteries (aorta or pulmonary artery)

but prevent backflow from arteries to ventricles

The valves are passive structures. They simply open or close depending on the relativepressures on either side of them.


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SPREAD OF EXCITATION

Excitation originates in Sino-atrial node (Primary pacemaker)

Atrioventricular node (Secondary pacemaker)

Bundle of His

Apex of ventricle

Purkinje fibres (Tertiary pacemaker)

Rest of ventricle

Features to note

1) Fibrous skeleton of the heart electrically isolates the atria from the ventricles.

AV node and Bundle of His are the only electrical connection between theatria and ventricles.

2) Propogation through the AV node is slow.

introduces a delay, allowing contraction of the atria to finish before the

ventricles contract.

3) Conducting system allows co-ordinated spread of excitation to ensure co-ordinated contraction and efficient pumping.

THE ELECTROCARDIOGRAM (ECG)

Indirectly reflects the electrical activity of the heart

As excitation sweeps over the heart at any instant some parts of the heart will bepositively charged while other parts are negatively charged.

This causes currents to flow in the medium surrounding the heart.

Because the body is a very good conductor these small currents can be detected atthe body surface.

The ECG is a recording of these small currents and reflects the depolarisation andrepolarisation of different regions of the heart.

The normal ECG has 3 main phases

P wave Atrial depolarisation

QRS complex Ventricular depolarisationT wave Ventricular repolarisation


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5 Phases of the cardiac cycle

Note: For simplicity, the following description concentrates on the left side of the heartand ejection of blood into the aorta (systemic circulation). Identical events occursimultaneously in the right side of the heart, but the pressures are much lower.

1. Passive Filling

Pressure in the left atrium is higher than pressure in the left ventricle.

Therefore the Atrio-Ventricular valve is open.

Blood flows from atrium into ventricle.

Pressure in the aorta is higher than pressure in the left ventricle.

Therefore the aortic valve is shut.

ECG is silent.

2. Atrial Contraction

Sino-Atrial node fires an action potential.

Atrium contracts (adding more blood into the ventricle).

Coincides with P wave of the ECG.

Pressure in the ventricle rises slightly because of added volume of blood.

Aortic valve is still shut.

NB: Phases 1 & 2 can be considered together as just the one phase of ventricular filling.

3. Isovolumetric Ventricular Contraction

Excitation spreads to ventricle

Ventricle begins to contract

QRS complex of the ECG

Pressure in the ventricle rises

A-V valve snaps shut when ventricular pressure rises above atrial pressure

First Heart Sound

Aortic valve is still closed

Ventricle is now sealed isovolumetric contraction

Ventricular pressure continues to rise sharply


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4. Ventricular Ejection

When ventricular pressure rises above aortic pressure the aortic valve opens

Blood is ejected from the ventricle into the aorta

A-V valve remains shut preventing backflow of blood into atrium

When blood has left the ventricle ventricular pressure starts to fall again and theventricle now begins to relax

T wave of the ECG occurs toward the end of the ejection phase

5. Isovolumetric Ventricular Relaxation

When ventricular pressure falls below aortic pressure the aortic valve snaps shut

Second Heart Sound

A-V valve is still shut

Ventricle is again sealed isovolumetric relaxation

Ventricular pressure continues to fall

When ventricular pressure falls below atrial pressure A-V valve opens again

back to phase 1

**** SEE, DAVIES et al., FIGURE 6.2.16 ****SALADIN, FIGURE 19.19

The Pressure-Volume Loop

Another way of depicting the ventricular pressure and volume changes during thecardiac cycle.

Phase plot of left ventricular pressure against left ventricular volume during thecardiac cycle.

The four sides of the loop represent the four basic phases of the cardiac cycle.

The area enclosed by the pressure-volume loop represents the external work doneby the heart

**** SEE, DAVIES et al., FIGURE 6.2.15 ****


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CONTROL OF CARDIAC OUTPUT

CARDIAC OUTPUT

Volume of blood pumped by each ventricle per minute

CARDIAC OUTPUT = HEART RATE X STROKE VOLUME

L/min beats/min L/beat

Stroke volume is the volume pumped per contraction

Stroke volume = end-diastolic volume end-systolic volume

Average values at rest

Heart Rate 70 beats/min

Stroke Volume 70 ml/beat

Cardiac Output = 70 beats/min x 70 ml/beat

= 4.9 litres/min

(i.e., approximately the total blood volume per minute)

In strenuous exercise cardiac output can increase 5 to 6 fold

up to 25 30 L/min

In highly trained athletes: up to 35 40 L/min

C0NTROL OF HEART RATE

Heart rate is controlled by the autonomic nervous system acting on pacemaker cells ofthe SA node (see Appendix at end of these notes).

1. Decreased by parasympathetic stimulation

2. Increased by sympathetic stimulation and circulating adrenaline

Other factors can influence heart rate (e.g., ionic imbalances in extracellular fluid -especially K

+concentration, body temperature) but these dont play a role in normal

control of heart rate.

Tachycardia = increase in heart rate

Bradycardia = slowing of heart rate

Cardiac Output can be changed by changing Heart Rate and/or Stroke Volume.


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There is an upper limit to heart rate.

cant go above about 200 beats/min

pumping becomes inefficient because there is not enough time betweencontractions to fill the ventricles with blood

Resting heart rate in a normal individual is 70/min

In a highly trained athlete it may be as low as 40/min

Gives greater potential (or reserve) for increase.

If resting HR is 70/min, going to 200/min is an 3x increase

If resting HR is 40/min, going to 200/min is a 5x increase

Another advantage of a low resting heart rate is that it is energetically less costly(i.e., the heart uses less oxygen at a lower heart rate).

A point of interest

Maximum heart rate decreases with age. Rates close to 200/min can be achieved byhealthy young adults but in older adults maximum heart rates (e.g., during intenseexercise) are less.

As an approximation: Maximum HR 220 age

CONTROL OF STROKE VOLUME

Stroke Volume strength of ventricular contraction

Stroke volume = end-diastolic volume end-systolic volume

Two major determinants

1. End-diastolic volume (degree of filling of the ventricles with blood)

2. Contractility of the cardiac muscle

Ejection Fraction

Stroke volume expressed as a fraction of the end-diastolic volume.

(Ejection Fraction = Stroke Volume/End-Diastolic Volume)

Typical values at rest: EDV = 120 ml, ESV = 50 ml

SV = 120 50 = 70 ml

EF = 70/120 = 0.6 = 60%

Important indicator of cardiac health (should be at least 55% in a healthy heart).

Increases when cardiac muscle contractility increases (can go up as high as 90% invigorous exercise).


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ROLE OF END-DIASTOLIC VOLUME

(Also referred to as preload)

As end-diastolic volume increases so to does stroke volume (up to a point)

Frank-Starling Law of the Heart

Underlying basis is the length-tension relation of cardiac muscle.

Increased filling of ventricles stretches the cardiac muscle cells.

As they are stretched they move up their length tension relation and contract withgreater force.

Cardiac muscle cells are normally at relatively short lengths(well below optimal length)

Control of stroke volume by end-diastolic volume is an intrinsic property of the heart

Increased venous return automatically causes an increase in stroke volume

Means of matching output to input (ventricles tend to eject as much blood as theyreceive).

Important in matching the output of the right and left sides of the heart.(Think about this. See Davies et al. page 548 Why is Starlings law important?)

Main Determinants of End-Diastolic Volume

1. Time available for filling

2. Venous pressure


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CHANGES IN CONTRACTILITY

A change in contractility is a change in contraction strength at the same musclelength (end-diastolic volume).

Changes in contractility are generally due to a change in the amount of Ca2+entering and being released in the cardiac muscle cells.

Contractility is increased by sympathetic stimulation

noradrenaline (and circulating adrenaline)

act on -receptors on cardiac muscle cells to increase Ca2+

entry and Ca2+

release from the sarcoplasmic reticulum

Contractility can also be altered by certain drugs and hormones, and ionic changesin the extracellular fluid.

Changes in contractility are also referred to as inotropic changes (cf chronotropic

changes which are changes in heart rate)

Agents that increase contractility are positive inotropic agents while agents thatdecrease contractility are negative inotropic agents.

EFFECT OF AFTERLOAD

Afterload is the pressure in the arterial system (aorta or pulmonary artery) thatresists ventricular ejection.

Before the ventricles begin to eject blood the pressure in them must rise higher thanthe pressure in the respective arterial system (refer to Cardiac Cycle).

High arterial pressure (high afterload) can reduce stroke volume.


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SUMMARY OF CONTROL OF CARDIAC OUTPUT

MEASURING CARDIAC OUTPUT

Fick Principle cardiac output determined from whole body oxygen consumption anddifference in oxygen concentration of arterial blood and mixed venous blood.

Dye dilution methods also based on the Fick principle but involves injection of anindicator substance into the circulation.

Doppler flow probe (noninvasive) Makes use of Doppler effect

Ultrasound pulses reflected by moving red blood cells

Gives a measure of the velocity of blood flow in ascending aorta

If cross-sectional area of the aorta is known (echocardiography) can calculatestroke volume and cardiac output.

CARDIAC OUTPUT


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ARTERIES,ARTERIOLES AND DISTRIBUTION OF BLOD FLOW

STRUCTURE OF BLOOD VESSELS

Walls of most blood vessels contain 3 basic layers.

Inner layer (tunica interna)

the endothelium

Consists of closely fitted endothelial cells that line the lumen of the blood vessel.

Plays an important role in controlling the diameter of the blood vessel byreleasing substances that either constrict (narrow) or dilate (widen) the bloodvessel.

Middle layer (tunica media)

Consists of circularly arranged smooth muscle and sheets of elastic tissue.

The circular smooth muscle can change the diameter of the blood vessel bycontracting or relaxing.

The elastic layer contributes to the elastic capacity (stretch and recoil) of theblood vessel wall.

Outer layer (tunica externa)

Loosely woven connective tissue (collagen) layer.

Protects and reinforces the blood vessel and helps anchor it to surroundingstructures.

The relative amount or thickness of the middle and outer layers varies between differenttypes of blood vessel.

*** See SALADIN, pp 751-752 & Figure 20.2 ***

Note: The wall of capillaries consists only of endothelial cells (see Lecture 5).

ARTERIES

Conduct blood away from the heart (conducting and distributing system)

Large arteries are thick walled with lots of elastic tissue in the wall (elastic arteries)

Act as a Pressure Reservoir

Arterial pressure goes up and down during the cardiac cycle pulse


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Key Point: Pressure in an elastic tube depends on

1. The volume of fluid in it, and

2. The distensibility of its walls

Flow of blood out of the heart is intermittent(only occurs during ventricular ejection phase of the cardiac cycle)

But blood flow through tissues and organs of the body is continuous WHY?

During systole blood enters the large arteries and stretches their elastic walls

pressure goes up

systolic pressure highest value

During diastole no more blood enters the large arteries but their elastic walls recoiland blood continues to flow into the smaller arteries, arterioles etc.

pressure falls as blood leaves the large arteries

diastolic pressure lowest value

Arteries have large diameters

Low resistance to flow

Not much loss of pressure as you go along the arteries

Summary

ELASTIC (pressure reservoir)

ARTERIES

LARGE DIAMETER (low resistance)

ARTERIOLES

Flow regulating system.

Control the proportional distribution of blood flow to the different organs andtissues of the body through changes in their diameter.

The blood flow requirements of different organs and tissues can vary substantiallyunder different circumstances (e.g., exercise).


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At Rest Moderate Exercise

Flow(ml/min)

% CO Flow(ml/min)

% CO % change inflow

Gut and Liver 1,350 27% 600 4.8% 56%Kidneys 1,000 20% 550 4.4% 45%Skin 450 9% 1,700 13.6% 370%Brain 650 13% 650 5.2% no change

Heart 150 3% 550 4.4% 367%Skeletal muscle 750 15% 8,000 64% 1066%Bone, other 650 13% 450 3.6% 30%Total CO 5,000 100% 12,500 100%

Recall that flow is given by the equation: F =P

R

P is the same for all organs/tissues (the mean arterial pressure).

Therefore it is the local resistance (R) that determines the flow through eachorgan/tissue.

The main thing determining the resistance to flow is the diameter of the arteriolesleading into the particular organ/tissue.

Can control the resistance, and hence the flow, by controlling the diameter of thearterioles.

Arterioles have smooth muscle in their walls. Orientated circularly.

Contraction of the smooth muscle

constriction of the arteriole

Relaxation of the smooth muscle

dilation of the arteriole

Arterioles are normally under some level of continuous contraction.

this allows for dilation by relaxing the level of contraction

or for constriction by increasing the level of contraction


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CONTROL OF ARTERIOLE RESISTANCE (DIAMETER)

LOCAL CONTROLS

1) LOCAL CHEMICAL CHANGES

Blood flow increases when tissue metabolic activity increases(active hyperemia)

Results from dilation of arterioles

relaxation of smooth muscle

caused by local chemical factors

[O2], [CO2], [metabolites] (eg, adenosine), [H+] Seen in all tissues, but especially important in skeletal muscle and the heart.

Other local chemicals can also affect arterioles

Local hormones (eg, histamine, prostaglandins)

Factors released from the endothelium (eg, nitric oxide)

2) LOCAL PHYSICAL INFLUENCES

a) Myogenic response to stretch (Pressure autoregulation)

Increased stretch increased contraction (constriction)

Decreased stretch decreased contraction (dilation)

Allows organs to maintain constant blood flow in the face of changes in the upstreampressure (mean arterial pressure).

particularly well developed in the brain (cerebral circulation)

b) Temperature

Heat dilation of arterioles

Cold constriction of arterioles

Reactive hyperemia

Period of increased blood flow following a period of occlusion.

Results from combined influence of local chemical and physical factors during theperiod of occlusion.

Local control of arterioles serves the local needs of specific tissues and organs.


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REFLEX CONTROLS

Serve to co-ordinate the needs of the whole body.

Important in regulating arterial blood pressure. (see lecture 16)

Most arterioles have a rich sympathetic nerve supply.

The density of the sympathetic nerve supply to the arterioles varies betweendifferent vascular beds (e.g., not very dense in the brain or in the heart)

Sympathetic nerves release noradrenaline.

acts on-receptors on smooth muscle

causes contraction (constriction of arteriole)

There is some level of resting sympathetic activity continuously present so the

smooth muscle is partially contracted.

Increased sympathetic activity constriction

Decreased sympathetic activity dilation

Note: There is no significant parasympathetic nerve supply to arterioles(except to genitals, and perhaps also some cerebral and coronary vessels).

HORMONAL INFLUENCES

ADRENALINE

Causes constriction in most areas (acting on -receptors).

Causes dilation when acting on arterioles with -receptors.(e.g., in skeletal muscle and in the heart)

Other hormones

Angiotensin II, Vasopressin

constrict arterioles

Atrial Naturietic Peptide, Bradykinin

dilate arterioles

THE ENDOTHELIUM

Plays an important role in controlling arteriole diameter.

Endothelial cells release both vasodilator (nitric oxide, prostacyclin) and vasoconstrictor(endothelin-1) substances.

Shear stress is an important stimulus for release of endothelium derived relaxingfactors.


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Veins and Venous Return of Blood to the Heart

VEINS

Collecting and blood return system

Volume Reservoir (about 60% of the total blood volume is in the systemic veins)

At venules: pressure 15 mmHg

In right atrium: pressure 0 mmHg

Therefore, there is only a small pressure gradient to drive return of blood back to the heart.

Veins must provide a low resistance pathway for flow of blood back to the heart.

Characteristics of Veins

Large diameters

- Therefore, low resistance to flow.

Thin walled and very distensible (compliant)

- Therefore, can hold large volumes of blood at relatively low pressure.- Volume Reservoir

VENOUS PRESSURE

Pressure difference between veins and right atrium

Represents the driving force for return of blood to the heart.

Right Atrial Pressure is sometimes also called Central Venous Pressure while pressure in theperipheral veins is called Peripheral Venous Pressure.

(**Always remember that the blood vessels are in a continuous loop, i.e., from aorta back toright atrium)

Venous Pressure is Determined by:

1. Volume of blood in the veinsAs for any elastic tube

2. Distensibility of vein walls

Smooth muscle is present in the walls of veins

Receives sympathetic nerve input.

Contraction of the smooth muscle stiffens the vein walls (decreases distensibility).


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Role of the sympathetic nervous system in venous return

Increased sympathetic stimulation to veins

Contraction of vein smooth muscle

Stiffening of vein walls

Decreases the distensibility

Increases Venous Pressure

Note: Veins have large diameters. When the smooth muscle contracts there is only a slightchange in diameter and so the resistance doesnt increase much. The main effect is a stiffeningof the walls.

ROLE OF VENOUS PRESSURE IN DETERMINING CARDIAC OUTPUT

Increased Venous Pressure(e.g. sympathetic stimulation)

Increases the volume of blood returned to the heart

Increases the End-Diastolic Volume

Increases Stroke Volume(Frank Starling Law)

Increases Cardiac Output

OTHER FACTORS THAT AID VENOUS RETURN

Skeletal Muscle Pump

Intermittent contractions of skeletal muscle squeeze on veins and push blood toward theheart.

This action relies on the presence of one-way valves in the veins.

Important in counteracting effect of gravity in upright posture.

Aids in increasing venous return during exercise.


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Respiratory Pump

Alternating changes in abdominal pressure and thoracic pressure during breathing exertexternal pressure on veins. Propels blood from abdominal veins into thorax.

During inspiration thoracic pressure drops and abdominal pressure increases. Inabdomen the veins get squeezed pushing blood into the thorax (venous valves onlyallow flow toward the heart).

Cardiac Suction

Atrioventricular valve is pulled down during contraction of the ventricle. This expands theatrial space and sucks blood from the veins into the atria.

When the ventricles relax and open out again they also suck blood into them from the atria.

Venous Valves

One-way valves.

Located at periodic intervals in most veins.

Allow flow toward the heart but prevent backflow.

Important for the actions of the skeletal muscle pump and respiratory pump.

Important in counteracting the effects of gravity when in an upright posture.

THE CRUCIAL IMPORTANCE OF VENOUS RETURN

The heart can only pump out whatever blood it has returned to it.

If venous return falls too low there is simply not enough blood in the heart for it to pump outan adequate stroke volume.

If this happens, cardiac output falls and not enough blood is delivered to the organs andtissues of the body a dangerous situation.

Importance of total circulating blood volume. Danger posed by haemorrhage.

Matching of Venous Return and Cardiac Outpu

In the normal functioning heart the output must equal the input.

to stop blood accumulating in the heart itself or in either the pulmonary or systemic sideof the system.

i.e., cardiac output must match venous return.

The Vascular Function Curve

Describes how venous return is related to right atrial pressure (see diagram).

When right atrial pressure is low (e.g., 0 mmHg) there is a good pressure gradient from theperipheral veins to the right atrium. Therefore, venous return is high.

When right atrial pressure increases the pressure gradient from the peripheral veins to theright atrium decreases. Therefore, venous return decreases.


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The Cardiac Function Curve (Ventricular Function Curve)

Describes the relationship between cardiac output and right atrial pressure (see diagram).

Basically this is the Frank-Starling Curve increased right atrial pressure increasesventricular filling (end-diastolic volume) thereby increasing stroke volume.

insert diagrams

Each of these curves is derived independently of the other.

The Vascular Function Curve describes the behaviour of the vascular system alone inreturning blood to the heart.

The Cardiac Function Curve describes the behaviour of the heart alone as a pump.

If these two curves are plotted together there is an intersection point.

this is where cardiac output equals venous return.

The intersection point defines the actual operating state of the heart under those particularconditions.


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The Vascular Function Curve can be shifted by things such as:

changes in venomotor tone (e.g., stiffening of the vein walls through sympatheticstimulation)

changes in blood volume

changes in the level of constriction or dilation of the upstream arterioles

The cardiac Function Curve can be changed by changes in cardiac contractility.

When either, or both, curves change the intersection point changes, representing a newoperating condition of the heart.

To get large changes you generally need to have shifts in both curves (e.g., duringexercise). Shows that the heart and blood vessels work together to achieve the desiredcardiovascular outcome.

Insert diagram

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