CARDIOVASCULAR PHYSIOLOGY

MED2031 Cardiovascular System Overview A/Prof Igor Wendt Room: F130, Department of Physiology Phone: 9905 2511 Email: Igor.Wendt@med.monash.edu.au Textbook References: Davies, et al. Human Anatomy & Physiology, Section 6 Saladin, Anatomy & Physiology, Chapters19 & 20

Why do we have a circulatory system? TRANSPORT FUNCTION 1. 2. 3. 4. Supply nutrients + O2 to organs and tissues Remove CO2 + waste products Co-ordinate body functions - transport chemical messengers (e.g., hormones) Defence mechanism - transport antibodies and white blood cells to sites of injury/infection Heat transfer (especially by circulation to skin)

COMPONENTS OF THE CIRCULATORY SYSTEM Fluid in the system Tubes through which the blood flows BLOOD

BLOOD VESSELS CARDIOVASCULAR SYSTEM

Pump to produce the flow

HEART

BLOOD Specialized cells suspended in a fluid Plasma: 93% water with dissolved substances e.g. electrolytes, proteins, nutrients, wastes, hormones dissolved gases 1) Red blood cells ~ 5 billion per ml (> 99% of all blood cells) - transport oxygen
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Cells:

2) 3)

White blood cells (leucocytes) - immune system Platelets - crucial role in blood clotting

HAEMATOCRIT = % volume of blood occupied by cells

55% plasma Centrifuge 45% red blood cells

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 The system is sealed. (operates at low pressure)

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.
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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 the flow of blood

ARTERIES

Have low resistance to flow. Conduct blood to organs and tissues with little loss of pressure. Act as pressure reservoirs. Smallest arteries branch into arterioles. Arterioles are the flow regulating system. Control resistance to flow and, therefore, the distribution of flow between the different organs and tissues. Site where substances are exchanged between the blood and cells of the body. Collect blood from capillaries. Return blood to the heart. Low resistance. Volume Reservoir Function

ARTERIOLES

CAPILLARIES

VENULES VEINS

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

FLOW OF FLUID THROUGH TUBES

Difference in pressure causes flow Flow is always from region of high pressure to region of lower pressure

P1 100 mmHg P1 100 mmHg P1 200 mmHg

P2 100 mmHg P2 50 mmHg P2 150 mmHg

P = 0 mmHg No flow

P = 50 mmHg Flow = 5 l/min

P = 50 mmHg Flow = 5 l/min (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

RESISTANCE TO FLOW
Flow is determined not only by P but also by the resistance to flow. 3 factors determine resistance 1) 2) 3) Viscosity of fluid ( viscosity resistance) Length of tube (R length of tube) Radius of tube (R

1 r4

Basic flow equation

F=

P R

Viscosity : blood is thicker than water At normal haematocrit At haematocrit At haematocrit ~ 45% viscosity of blood ~ 60% viscosity of blood ~ 25% viscosity of blood 3 x that of water 7 x that of water 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) of the 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)

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 viscosity of the blood increases resistance and reduces flow to all organs, including the skeletal muscles 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.

MED2031

Cardiovascular Physiology

Igor Wendt, Lecture 2

THE HEART AND CARDIAC CONTRACTION

Muscular organ in chest Enclosed in a fibrous sac Pericardium which protects the heart and anchors it to surrounding structures. The walls of the heart are composed mostly of a special type of muscle cell - cardiac muscle (myocardium) Lined on the inner surface by the endocardium (endothelial cells) and on the outer surface by the epicardium (connective tissue and fat) Two functional sides Left Heart and Right Heart Right side receives blood from the systemic circulation and pumps out into the pulmonary circulation (low pressure). Left side receives blood from the pulmonary circulation and pumps out into the systemic circulation (high pressure). Each side has two chambers an atrium and a ventricle **** See, SALADIN, Figure 19.6 **** Note: The left ventricle has a much thicker wall than the right ventricle because it has to do much more work (i.e., generate much higher pressure) Sequence of blood flow through the heart

via systemic circulation Left Ventricle Right Atrium

Left Atrium via pulmonary circulation (lungs)

Right Ventricle

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 **** See, SALADIN, Figures 19.6 to 19.9 **** The valves are passive structures. They simply open or close depending on the relative pressures 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 from ventricles (see lecture notes on Electrical Acrivity of the Heart)

CARDIAC MUSCLE
Similarities to Skeletal Muscle

Unique to the heart.

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 **** See, SALADIN, Figure 19.11 **** 2

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 contraction of the heart muscle.

A point of interest In 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

EXCITATION-CONTRACTION COUPLING IN CARDIAC MUSCLE Action Potential Depolarisation of membrane and T-tubules

Voltage-dependent Ca2+ channels in membrane open

Ca2+ enters from extracellular space (Ca2+ influx)

Triggers release of more Ca2+ from the sarcoplasmic reticulum Ca2+-induced Ca2+ release

Intracellular Ca2+ concentration rises

Ca2+ binds to troponin

Cross-bridge cycle starts Contraction

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

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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 filament mechanism 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 of the heart with blood. o o Increased filling stretches the cardiac muscle cells They contract with greater force as a result (move up the ascending part of the length force relation)

Changes in calcium release

In a normally contracting heart not enough calcium is released with each action potential to 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 the contraction 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 calcium channels (i.e., how trigger influx there is). The amount of calcium released by the calcium-induced calcium release mechanism depends on these two factors

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. **** See, SALADIN, Figure 19.10 **** Impairment of the coronary blood supply (coronary artery disease or blockage) has serious and 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)

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 to cell). 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

Excitation originates in

Sino-atrial node

(Primary pacemaker)

Atrioventricular node (Secondary pacemaker) Bundle of His Apex of ventricle Purkinje fibres 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 the atria and ventricles. 2) Propagation through the AV node is slow. introduces a delay, allowing contraction of the atria to finish before the ventricles contract. 3) Propagation through the Purkinje fibres is faster than through the normal ventricular cardiac cells. 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-ordinated contraction and efficient pumping. (Tertiary pacemaker)

Disorders of excitation (Arhythmias)

Atrial flutter AV node block - partial - complete

Block in conducting system Right or Left Bundle Branch block Ectopic beats (extra beats) 2

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 chest wall).

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 voltageactivated 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 to the potassium equilibrium potential). Ventricular cardiac muscle cells do not normally exhibit any spontaneous (pacemaker) electrical activity. 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

REGULATION OF HEART RATE SA node is the normal pacemaker Has intrinsic rhythm of 100/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+ channels and 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+ channels and 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 Rat Etruscan shrew Blue whale C0NTROL OF HEART RATE Heart rate is controlled by the autonomic nervous system acting on pacemaker cells of the SA node. 4 70/min 300/min 1000/min 10/min

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 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 by healthy young adults but in older adults maximum heart rates (e.g., during intense exercise) are less. As an approximation: Maximum HR 220 age

MED2031

Cardiovascular Physiology

Igor Wendt, Lecture 5

EVENTS IN THE CARDIAC CYCLE

The heart alternately contracts and relaxes in a rhythmic and coordinated fashion to achieve effective 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 heart valves, 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 relative pressures on either side of them. 1

SPREAD OF EXCITATION Excitation originates in Sino-atrial node (Primary pacemaker)

Atrioventricular node (Secondary pacemaker) Bundle of His Apex of ventricle Purkinje fibres Rest of ventricle (Tertiary pacemaker)

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 the atria 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 coordinated 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 be positively 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 at the body surface. The ECG is a recording of these small currents and reflects the depolarisation and repolarisation of different regions of the heart. The normal ECG has 3 main phases P wave QRS complex T wave Atrial depolarisation Ventricular depolarisation 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 heart and ejection of blood into the aorta (systemic circulation). Identical events occur simultaneously 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 the ventricle 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 the cardiac cycle. Phase plot of left ventricular pressure against left ventricular volume during the cardiac 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 done by the heart **** SEE, DAVIES et al., FIGURE 6.2.15 ****

MED2031

Cardiovascular Physiology

Igor Wendt, Lecture 6

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 Stroke Volume Cardiac Output 70 beats/min 70 ml/beat = 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 Cardiac Output can be changed by changing Heart Rate and/or Stroke Volume.

C0NTROL OF HEART RATE Heart rate is controlled by the autonomic nervous system acting on pacemaker cells of the 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

There is an upper limit to heart rate. cant go above about 200 beats/min pumping becomes inefficient because there is not enough time between contractions 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 by healthy young adults but in older adults maximum heart rates (e.g., during intense exercise) 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 EF = 120 50 = 70 ml = 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% in vigorous 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 with greater 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 they receive). 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 muscle length (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 changes in 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 that decrease contractility are negative inotropic agents.

EFFECT OF AFTERLOAD Afterload is the pressure in the arterial system (aorta or pulmonary artery) that resists ventricular ejection. Before the ventricles begin to eject blood the pressure in them must rise higher than the 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

CARDIAC OUTPUT

MEASURING CARDIAC OUTPUT

Fick Principle cardiac output determined from whole body oxygen consumption and difference in oxygen concentration of arterial blood and mixed venous blood. Dye dilution methods also based on the Fick principle but involves injection of an indicator 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 calculate stroke volume and cardiac output.
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MED2031

Cardiovascular Physiology

Igor Wendt, Lecture 7

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 by releasing substances that either constrict (narrow) or dilate (widen) the blood vessel. 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 by contracting or relaxing. The elastic layer contributes to the elastic capacity (stretch and recoil) of the blood vessel wall. Outer layer (tunica externa) Loosely woven connective tissue (collagen) layer. Protects and reinforces the blood vessel and helps anchor it to surrounding structures. The relative amount or thickness of the middle and outer layers varies between different types 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

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 recoil and 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 and tissues of the body through changes in their diameter. The blood flow requirements of different organs and tissues can vary substantially under different circumstances (e.g., exercise).

At Rest
Flow (ml/min) Gut and Liver Kidneys Skin Brain Heart Skeletal muscle Bone, other Total CO 1,350 1,000 450 650 150 750 650 5,000 % CO 27% 20% 9% 13% 3% 15% 13% 100%

Moderate Exercise
Flow (ml/min) 600 550 1,700 650 550 8,000 450 12,500 % CO 4.8% 4.4% 13.6% 5.2% 4.4% 64% 3.6% 100% % change in flow 56% 45% 370% no change 367% 1066% 30%

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 each organ/tissue. The main thing determining the resistance to flow is the diameter of the arterioles leading into the particular organ/tissue. Can control the resistance, and hence the flow, by controlling the diameter of the arterioles. 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

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 Decreased stretch increased contraction (constriction) decreased contraction (dilation)

Allows organs to maintain constant blood flow in the face of changes in the upstream pressure (mean arterial pressure). particularly well developed in the brain (cerebral circulation) b) Temperature Heat Cold dilation of arterioles 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 the period of occlusion.

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

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 between different 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 Decreased sympathetic activity constriction 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 relaxing factors.
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MED2031

Cardiovascular Physiology

Igor Wendt, Lecture 8

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 the peripheral veins is called Peripheral Venous Pressure. (**Always remember that the blood vessels are in a continuous loop, i.e., from aorta back to right atrium) Venous Pressure is Determined by: 1. Volume of blood in the veins As 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).

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 slight change in diameter and so the resistance doesnt increase much. The main effect is a stiffening of 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 the heart. 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.

Respiratory Pump Alternating changes in abdominal pressure and thoracic pressure during breathing exert external pressure on veins. Propels blood from abdominal veins into thorax. During inspiration thoracic pressure drops and abdominal pressure increases. In abdomen the veins get squeezed pushing blood into the thorax (venous valves only allow flow toward the heart). Cardiac Suction Atrioventricular valve is pulled down during contraction of the ventricle. This expands the atrial 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 out an adequate stroke volume. If this happens, cardiac output falls and not enough blood is delivered to the organs and tissues 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 side of 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 the peripheral veins to the right atrium. Therefore, venous return is high. When right atrial pressure increases the pressure gradient from the peripheral veins to the right atrium decreases. Therefore, venous return decreases. 3

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 increases ventricular filling (end-diastolic volume) thereby increasing stroke volume.
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Each of these curves is derived independently of the other. The Vascular Function Curve describes the behaviour of the vascular system alone in returning 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 particular conditions. 4

The Vascular Function Curve can be shifted by things such as: changes in venomotor tone (e.g., stiffening of the vein walls through sympathetic stimulation) 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 new operating condition of the heart. To get large changes you generally need to have shifts in both curves (e.g., during exercise). Shows that the heart and blood vessels work together to achieve the desired cardiovascular outcome.

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