Cardiology SAQ’s

Anaesthesia Primary

The Cardiovascular System- Overview I

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The basic anatomy of the heart consists of two atria and two ventricles that provide two separate circulations in series.

The right heart is a low pressure pump which delivers blood to the pulmonary circulation, a low-resistance and high-capacitance vascular bed.

The left side of the heart is a high pressure pump that provides output for the systemic circulation, a high resistance circulation which has a variety of vascular beds that run in parallel and the proportion of the CO is determined by the vascular resistance vessels, the peripheral arterioles

The functions of the cardiovascular system are: Supply of O2 and removal of CO2 Delivery of nutrients and removal of metabolic waste products Delivery of hormones and vasoactive substances to target cells. Role in immunity Temperature regulation

The Cardiovascular System- Overview II

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The pulsatile output of the left ventricle is converted to continuous flow by the elastic properties of the aortic wall, the presence of resistance in the peripheral vessels and the prevention of retrograde flow by the aortic valve Windkessel Effect

The high SBP allows the CO to be rapidly distributed between different organs and provides sufficient hydrostatic pressure for filtration in the glomeruli

The systemic arterial blood pressure is the fundamental monitored and regulated variable of the CVS.

The arterioles: Determine the distribution of CO around the various organs by their variable resistance; Determine arterial blood pressure by influencing total peripheral resistance and: Reduce intravascular pressure upstream of the thin-walled capillaries

The capillaries: Consist of only a single layer of endothelium and provide a very large surface area for the exchange of

nutrients and wastes between the tissues and the blood that flows slowly through them The lymphatics

Thin walled vessels that are permeable to protein and collect any excess fluid and protein from the interstitial spaces and drain into the thoracic veins

The veins and venules Low resistance vessel conduits for the return of blood to the right atrium The large veins normally contain 60% of the blood volume and their capacitance can be altered by nerve

activity.

Distribution of Blood volume in CVSTotal blood volume is 5-6 L in and male and 4-5L in Female Supine

76% in systemic circulation 60% in veins 10% in arteries and arterioles 6% in capillaries

16% in Pulmonary circulation 8% in Arteries 5% in veins 3% in capillaries

8% in the heart

Erect 85% in systemic circulation

70% in veins 10% in arteries and arterioles 5% in capillaries

9% in Pulmonary circulation 8% in Arteries 5% in veins 3% in capillaries

6% in the heart

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Cardiac Anatomy I

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The heart comprises four chambers, and is divided into a right and left side, each with an atrium and a ventricle.

The atria act as reservoirs for venous blood, with a small pumping action to assist ventricular filling.

In contrast, the ventricles are the major pumping chambers for delivering blood to the pulmonary (right ventricle) and systemic (left ventricle) circulations. The left ventricle is conical in shape and has to

generate greater pressures than the right ventricle, and so has a much thicker and more muscular wall.

Four valves ensure that blood flows only one way, from atria to ventricle (tricuspid and mitral valves), and then to the arterial circulations (pulmonary and aortic valves).

The myocardium consists of muscle cells which can contract spontaneously, even if all nerves to the heart are cut. This feature is called autorhythmicity.

The autonomic nervous system's are responsible for speeding up or slowing down the heart beat. 

Cardiac Anatomy II

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Cardiac muscle cells have striations similar to skeletal muscle, being made up of sarcomeres, containing myosin thick filaments(H Band) and actin thin filaments(I band), which are attached to Z lines The thick filaments are composed of myosin Each thick filament is surrounded by 6 thin filaments, composed of a double

spiral of actin molecules in combination with tropomyosin and troponin. When compared to skeletal muscle, cardiac muscle cells are shorter and

thicker consisting of branching mononucleated cells which connect by means of intercalated disks to form a functional syncytium, in which all cells act as a single unit

The intercalated discs provide strong mechanical attachments between adjacent cells and enable the heart to contract forcefully without ripping the fibres apart.

In cardiac and smooth muscle the action potential travels from cell to cell through low resistance pathways alongside the intercalated disc = gap junctions.

The electrical signal easily crosses these gap junctions and no chemical transmitter is involved. This spreads the excitation from one cell to another and causes cardiac and most smooth muscle to contract as a unit.

Cardiac cells have a richer supply of mitochondria as they are involved in much greater contractile activity.  For instance, your heart beats about 70 times per minute for your entire life including prenatal life.

The cardiac muscle cells are arranged in spiral layers anchored to the fibrous ring base of the heart which encircles the chambers.

During ventricular contraction the heart is pulled downward and the heart rotates to the right and this can be palpated as the apex beat.

The left ventricle contracts in a concentric, squeezing fashion, whilst right ventricular contractions is more of a bellows action

Cardiac Anatomy III Coronary Circulation

Coronary arteries leave the aorta behind the semilunar valves. This means that they fill during ventricular diastole.

The right coronary artery branches to smaller arteries including the marginal, which leads down the margin or edge of the right ventricle.

The main portion of the right coronary artery proceeds to the back of the heart becoming the posterior interventricular artery. RCA Dominant in 50% of people LAD Dominant in 20% of people Co-dominant in 30% of people

The left coronary artery divides to form the circumflex which curves to the back of the heart, and the anterior descending which follows the septum between the two ventricles.

The arteries anastomose to provide collateral circulation to the ventricular myocardium.

Coronary veins drain the myocardium Great cardiac vein: drains the anterior interventricular area Middle cardiac vein: drains the posterior interventricular area small cardiac vein : drains the right atrial area

These drains directly into the right atrium via either the coronary sinus (75%) or the anterior cardiac vein (22%)

The remainder drains through thebesian vessels (3%) directly into all the chambers of the heart

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The cardiac cycle The cardiac cycle is the sequence of electrical and mechanical

events during the course of a single heartbeat There is a similar cycle on both sides of the heart, but the

pressures in the right ventricle and pulmonary arteries are less than those in the left ventricle and aorta.

Systole refers to contraction, while diastole refers to relaxation. Both contraction and relaxation can be isovolumetric , when changes in intraventricular pressure occur without a change in length of the muscle fibres.

The cycle starts with depolarisation at the sinoatrial node leading to atrial contraction. Until this time blood flow into the ventricles has been passive, but the atrial contraction increases filling by 20-30%.  

Ventricular systole causes closure of the atrioventricular valves (1st heart sound), and contraction is isovolumetric until intraventricular pressures are sufficient to open the pulmonary and aortic valves, when the ejection phase begins.

The volume of blood ejected is known as the stroke volume. At the end of this phase ventricular relaxation occurs, and the pulmonary and aortic valves close (2nd heart sound).

After isovolumetric relaxation ventricular pressures fall to less than atrial pressures. This leads to opening of the atrioventricular valves and the start of ventricular diastolic filling. The whole cycle then repeats following another impulse from the sinoatrial node.

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Electrophysiology of the heart Myocardial contraction results from a change in voltage across the cell

membrane (depolarisation), which leads to an action potential. This impulse starts in the sinoatrial (SA) node, a collection of

pacemaker cells located near the junction of the right atrium and superior vena cava.

These specialised cells depolarise spontaneously, and cause a wave of contraction to pass across the atria via atrial conduction pathways to the AV Node.

Following atrial contraction, the impulse is delayed at the atrioventricular (AV) node, located in the septal wall of the right atrium.

From here His-Purkinje fibres allow rapid conduction of the electrical impulse via right and left branches, causing almost simultaneous depolarisation of both ventricles, approximately 0.2 seconds after the initial impulse has arisen in the sinoatrial node.

Depolarisation of the myocardial cell membrane causes a large increase in the concentration of calcium within the cell, which in turn causes contraction by a temporary binding between two proteins, actin and myosin.

The cardiac action potential is much longer than that of skeletal muscle, and during this time the myocardial cell is unresponsive to further excitation. 

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Cardiac Action Potentials Compared to nerve action potentials,

cardiac action potentials last much longer Nerve – 1ms

Changes in Na+ and K+ permeability Cardiac- 250ms

Longer due to changes in Ca2+ permeability Two main types of action potential

Fast response of normal atrial and ventricular muscle cells and in the Purkinje Fibres

Slow response cardiac action potential seen in the SA and AV Nodes Display properties of

Automaticity Ability to depolarise automatically

Rhythmicity Ability to maintain a regular discharge rate

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The Ionic Basis For The Fast-response Cardiac Action Potential

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There are 5 phases Phase 0

The cell is depolarised from the resting membrane potential by a rise in membrane sodium permeability

Fast sodium channels open, similar to those in nerves and are sensitive to tetrodotoxin

Potassium conductance decreases Phase 1

Partial repolarization due to rapid decrease in sodium permeability

Phase 2-Plateau The cell membrane permeability to calcium rises,

maintaining depolarisation. Sodium conductance continues to decline slowly

Phase 3-Repolarisation Potassium, sodium and calcium permeability

return towards normal Phase 4- RMP

The membrane potential is mainly governed by potassium permeability

Cardiac Calcium Channels Two types of calcium channels are involved in the

cardiac action potential Long-lasting: L-Type and Transient: T-Type The L-Type produce a long lasting calcium current and

are the predominant calcium channel in the heart and begin to open during the action potential upstroke (phase 0) when the membrane is depolarised to -10mV The calcium channel blockers nifedipine and verapamil

block L-type channels while Catecholamines increase the activation of L-type calcium channels

T-type channels open briefly before L-type channels when the membrane potential is -70mV and are not affected by catecholamines

Refractory periods The ventricular muscle action potential lasts for 250ms Of this the ARP accounts for the first 200 ms and the

RRP for the other 50ms The ARP extends into phase 3 and during this period

the cell will not respond to further excitation ARR means that the heart cannot react to a stimulus no

matter how large it is, during the RRP the heart can react to a supramaximal stimulus

Refractory periods ensure that the AP is transmitted in one direction only and also restrict the maximum rate of contractions

The Ionic Basis For The Slow-response Cardiac Action Potential The SA node has no resting state Rather there is a pacemaker potential which

generates cardiac automaticity Phase 1 and 2 are absent in the SA node as

there is no spike or plateau Phase 4

The pacemaker potential is caused by a fall in membrane potassium permeability and an increase in the slow inward current

Because of the high sodium ion concentration in the extracellular fluid outside the nodal fiber, as well as a moderate number of already open sodium channels, positive sodium ions from outside the fibers normally tend to leak to the inside.

Therefore, between heartbeats, influx of positively charged sodium ions causes a slow rise in the resting membrane potential in the positive direction.

Thus, the “resting” potential gradually rises between each two heartbeats.

This pacemaker activity brings the cell to the threshold potential

Phase 0 - Depolarisation When the potential reaches a threshold voltage of

about -40 millivolts, the sodium-calcium channels (T-type) become “activated,” thus causing the action potential.

Therefore, basically, the inherent leakiness of the sinus nodal fibers to sodium and calcium ions causes their self-excitation

Phase 3 - Repolarisation Increased potassium permeability and the outward

flow of ions and inactivation of Na+/Ca2+ channels Consequently, there is no sharp, rapid depolarizing

spike before the plateau, as there is in other parts of the conduction system and the atrial and ventricular fibers

A cycle of K+ Ca2+ K+ produces the SA node automaticity

PNS increases the membrane potassium permeability of the SA node hyperpolarisation and inhibition of spontaneous cardiac activity

SNS has the opposite effect by opening calcium channels

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Pacemaker discharge rates Pacemaker discharge rate is controlled primarily by ANS PNS

Vagal stimulation of SA Node , membrane hyperpolarization and the slope of the phase 4 is decreased

ACh released at the nerve endings increases the K+ conductance of nodal tissue.

This action is mediated by M2 receptors, GPLR linked to a special set of K+ channels. The resulting IK slows the depolarizing effect of Ih

The result is a decrease in firing rate. Strong vagal stimulation may abolish spontaneous discharge for some time.

SNS stimulation of the sympathetic cardiac nerves depolarizing effect

of Ih, and the rate of spontaneous discharge increases. NA secreted by the sympathetic endings binds to 1 receptors,

intracellular cAMP opening of L channels, increasing Ca2+ and the rapidity of the depolarization phase of the impulse.

Other The rate of discharge of the SA node and other nodal tissue is

influenced by temperature and by drugs. The discharge frequency is increased when the temperature rises,

and this may contribute to the tachycardia associated with fever. Digitalis depresses nodal tissue and exerts an effect like that of

vagal stimulation, particularly on the AV node.

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Draw and label a lead II ECG tracing for one cardiac cycle, indicating normal values. What is the PR interval and what factors influence it? (July07: 50%) The PR Interval

The time between the beginning of the P wave and the beginning of the QRS complex is the interval between the beginning of electrical excitation of the atria and the beginning of excitation of the ventricles. AKA PQ interval

The time taken for excitation to spread from SA node through the atrial muscles, and the AV node, down the bundle of His and into the ventricular muscles.

Most of the conduction delay during this segment is due to slow conduction within the AV node.

The normal PR interval is 120 to 200 ms in duration. PR interval is Shortened with

increasing HR Pacemaker located close to the AV node

PR interval is Lengthened with Decreasing HR Increased Vagal tone Hypokalaemia Marked Hyperkalaemia Hypercalcaemia Hypermagnesmia In general, when the P-R interval increases to greater than 0.20 second, the P-R

interval is said to be prolonged, and the patient is said to have first degree incomplete heart block.

The P-R interval seldom increases above 0.35 to 0.45 second because, by that time, conduction through the A-V bundle is depressed so much that conduction stops entirely

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ECG I The electrocardiogram is composed of waves and

complexes. Waves and complexes in the normal sinus rhythm are the P wave, PR Interval, PR Segment, QRS Complex, ST Segment, QT Interval and T wave (shown right). 

The P wave P waves are caused by atrial depolarization. In normal sinus rhythm, the SA node acts as the

pacemaker. The electrical impulse from the SA node spreads over

the right and left atria to cause atrial depolarization. The P wave contour is usually smooth, entirely

positive and of uniform size. The P wave duration is normally less than 0.12 sec

and the amplitude is normally less than 0.25 mV. A negative P-wave can indicate depolarization arising

from the AV node. Note that the P wave corresponds to electrical impulses

not mechanical atria contraction. Atrial contraction begins at about the middle of the P wave and continues during the PR segment. A Wigger’s diagram can be used to illustrate that the left atrial pressure beginning to rise at about half way through the P-wave. Increase in atrial pressure indicates atrial contraction

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ECG II

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The PR interval (200ms) The portion of the ECG wave from the beginning of the P wave to the beginning of the QRS

complex. The time taken for excitation to spread from SA node through the atrial muscles, and the AV

node, down the bundle of His and into the ventricular muscles. Most of the time is taken up by the delay in the AV node. If the PR interval is very short, either the atria have been depolarised from close to the AV

node or there is abnormally fast conduction from the atria to the ventricles. The PR segment

The portion on the ECG wave from the end of the P wave to the beginning of the QRS complex, lasting about 0.1 seconds.

The PR segment corresponds to the time between the end of atrial depolarization to the onset of ventricular depolarization.

The PR segment is an isoelectric segment, that is, no wave or deflection is recorded. During the PR segment, the impulse travels from the AV node through the conducting tissue

(bundle branches, and Purkinje fibres) towards the ventricles. Most of the delay in the PR segment occurs in the AV node. 

Although the PR segment is isoelectric, the atria are actually contracting, filling the ventricles before ventricular systole. A Wigger’s diagram can be used to illustrate the increase in atrial pressure during the PR segment. 

ECG III

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The QRS complex (120ms) In normal sinus rhythm, each P wave is followed by a QRS complex. The QRS complex represents the time it takes for depolarization of the ventricles. Activation of the anterioseptal region of the ventricular myocardium corresponds to the

negative Q wave. The Q wave is not always present.

Activation of the rest of the ventricular muscle from the endocardial surface corresponds to the rest of the QRS wave.

The R wave is the point when half of the ventricular myocardium has been depolarized. Activation of the posteriobasal portion of the ventricles give the RS line. The normal QRS duration range is from 0.04 to 0.12 s measured from the initial deflection of

the QRS from the isoelectric line to the end of the QRS complex. Normal ventricular depolarization requires normal function of the right and left bundle

branches. A block in either the right or left bundle branch delays depolarization of the ventricles, resulting in a prolonged QRS duration.

The QRS complex precedes ventricular contraction. Ventricular contraction, indicated by a Wigger's diagram as an increase in the ventricular pressure,

beginning at about half-way through the QRS complex and continues to the end of the T-wave. Pumping of blood does begins when ventricular pressure exceeds aortic pressure, causing the semi lunar valves to open. This is normally at the end of the QRS complex and start of ST segment.

ECG IV

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The ST Segment The ST segment represents the period from the end of ventricular depolarization to the beginning of

ventricular repolarisation. The ST segment lies between the end of the QRS complex and the initial deflection of the T-wave and is

normally isoelectric. It is clinically important if elevated or depressed as it can be a sign of ischemia and hyperkalemia. Although the ST segment is isoelectric, the ventricles are actually contracting.

The QT interval (400 ms) The QT interval begins at the onset of the QRS complex and to the end of the T wave. It represents the time between the start of ventricular depolarization and the end of ventricular

repolarisation. It is useful as a measure of the duration of repolarisation. The QT interval will vary depending on the heart rate, age and gender. It increases with bradycardia and

decreases with tachycardia. Men have shorter QT intervals (0.39 sec) than women (0.41 sec). The QT interval is influenced by electrolyte balance, drugs, and ischemia.

The T wave The T wave corresponds to the rapid ventricular repolarisation. The wave is normally rounded and positive. The T wave can become inverted, peaked or flattened due to electrolyte imbalance, hyperventilation, CNS

disease, ischemia or myocardial infarction.

Briefly discuss the interaction of the action potential duration and conduction velocity in the ventricular myocardium and its effect on myocardial performance After the initial spike the membrane remains depolarised

for about 0.3 seconds in ventricular muscle, exhibiting the plateau shown, followed at the end by abrupt repolarisation

The presence of the plateau means that cardiac muscle contractions last 3-15 times as long as skeletal muscle

The plateau is the result of slow Ca2+ channels which remain open for several 10ths of a second Ca2+ influx.

These Ca2+ ions play an important role in helping excite the muscle contraction process, by triggering the sarcoplasmic reticulum to release more Ca2+

The speed of conduction of the cardiac impulse means that it takes 0.22 sec to reach the distal parts of the ventricle

At the resting heart rate this allow the entire ventricle to beat as one unit efficacy

AV delay between atrial and ventricular excitation permits optimal ventricular filling during atrial contraction

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Draw a labelled diagram of a cardiac action potential highlighting the sequence of changes in ionic conductance. Explain the terms threshold, excitability and irritability with the aid of a diagram

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Threshold The level of depolarisation at which a self propagating action potential is triggered

Excitability Refers to the ease with which myocardial cells can respond to a stimulus by

depolarising. If a cell can respond to a smaller stimulus than another cell, it is said to be more excitable.

Rate of rise of phase 0- slope of Irritability

Used in context of a resting myocardial cell during phase 4 and is used to either indicate either:

The size of the stimulus required to depolarise the cell, ie less distance between RMP and Threshold

To describe the ease with which an arrhythmia may be induced Automaticity

Property of heart which enables it to initiate its own heart beat In some myocardial cells (SA & AV nodes) the resting potential is not stable during

stage 4. Here the RMP spontaneously decreases towards the threshold potential An intrinsic property that does not require any external nervous or chemical input

to occur The cells with the fastest depolarisation to threshold set the heart rate and these

cells function as the pacemaker of the heart, usually the SA node. Rhythmicity

Automaticity is responsible for Rhythmicity Following depolarisation, the membrane repolarises and then the sequence of

spontaneous depolarisation occurs again. The predictable regularity of this sequence of events gives the heart a regular

rhythm This is known as the property of Rhythmicity

Absolute Refractory Period The period of time following the onset of the Action potential, during which the cell

cannot be stimulated no mater how large the stimulus It last from the onset of the action potential to about midway through the

repolarisation that occurs in phase 3 in ventricular cells

Phase 0 Rapid depolarisation due to opening of fast sodium channels increasing sodium entry

Phase 1 Partial repolarisation due to closure of fast sodium channel decreasing sodium entry

Phase 2 Plateau Opening of slow Calcium channels increase Calcium entry & net Potassium efflux through multiple channels

Phase 3 Slow Calcium channels close decreasing calcium entry ongoing Potassium efflux rapidly returns membrane potential to resting level

Phase 4 The RMP is mainly governed by potassium and is maintained by Na/K ATPase

List The Determinants Of Coronary Blood Flow I Resting coronary blood flow ≈ 250ml/min or 5% of CO Mention Ohm’s Law I= V/R therefore flow is affected by those physiological factors that alter Pressure

or Resistance Describe the vasculature Then mention the following High O2 consumption relative to its mass and a large resting A-V O2 difference

At rest the myocardial O2 delivery is ~10 mLO2min-1100 g-1 total requirement of 30 mLO2 min-1

20x skeletal muscle The myocardial extraction ≈ 70% much higher than normal 25% The PO2 of coronary sinus is 20mmHg. coronary venous content is only 50 mLO2L-1

In severe exercise there is little further decrease in venous O2 content. myocardial O2 consumption coronary flow because of high basal O2 extraction Heart cannot develop O2 debt.

The tone of the coronary arterioles is high at rest and the coronary circulation is controlled primarily by local metabolic factors, although there is some degree of myogenic control

Metabolic Autoregulation Coronary flow can increase 4- 5 times myocardial metabolic activity release of vasodilatory metabolites from myocardium into interstitial fluid

Coronary Blood flow. Counteracts any sympathetically mediated coronary vasoconstriction The increased flow occurs mostly in diastole, especially in LV

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List The Determinants Of Coronary Blood Flow II

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Extravascular Compression (Extracoronary Resistance) Describes the external compression produced by myocardial contraction during the cardiac cycle Coronary blood flow is reduced to zero in early systole The squeezing effect is greatest at the endocardial levels and least towards the epicardium The bulk of coronary blood flow occurs in diastole

Coronary Perfusion Pressure (CPP) The driving pressure for the coronary circulation Measured as aortic diastolic pressure (ADP minus the larger of LV diastolic pressure or RA pressure (~coronary

sinus pressure) As LV diastolic pressure and RA pressure are usually much less than ADP CPP ≈ ADP Autoregulation operates over a range of CPP 60-180mm Hg If CPP changes suddenly, coronary vessels respond by dilating or constricting to dampen dramatic surges or falls

in coronary blood flow Autonomic Nervous System

Activation of the SNS tends to produce an increase in coronary blood flow This occurs as a net result of increased metabolic demand in the face of negative effects of increased contractility

and HR on the coronary blood flow Tachycardia time spent in systole period of restricted inflow However, this mechanical reduction in mean coronary flow is overridden by the coronary dilation associated with increased

metabolic activity Under blockade coronary vessels constrict in response to SNS Stimulation of the Vagus nerve produces slight coronary vasodilation The reverse is true of bradycardia

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Describe the effects of tachycardia on myocardial oxygen supply and demand in a normal heart I High oxygen extraction of the cardiac muscle means that

coronary blood flow must increase when myocardial oxygen consumption increases

The tone of the coronary arterioles is high at rest and the coronary circulation is controlled primarily by local metabolic factors, although there is some degree of myogenic control

The driving pressure in the coronary circulation is the aortic diastolic pressure, but this is affected by compression of the coronary vessels during ventricular contraction

This is especially important in the LV; in early systole there is zero LV blood flow LV blood flow occurs mostly in diastole Subendocardial flow in the LV ceases during systole and is most

susceptible to ischemia RV peak pressure 25mm Hg vs. 120 mm Hg in LV blood flow

in systole During diastole pressure in coronary vessels falls to 80 mm Hg

and LV 2 mm Hg no compression of vessels Diastole occupies 2/3 of cardiac cycle 85% of LV and 70% of RV blood flow occurs during diastole Thus a pressure nearer the aortic diastolic pressure, not the MAP,

becomes the 1° determinant of the pressure gradient for coronary blood flow

Describe the effects of tachycardia on myocardial oxygen supply and demand in a normal heart II

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The major determinants of myocardial oxygen demands are: Basal metabolism 25% Wall Tension 30-40% Heart Rate 15-25% Myocardial contractility 10-15% External work 10-15%

Tachycardia has several effects on myocardial oxygen demand It increase the work done by the heart O2 demand Decreases amount of time in diastole perfusion time

Because of the high O2 extraction, the increased cardiac oxygen demand is met mainly by an increase in coronary blood flow Increase from 250 mLmin-1 up to 1250 mLmin-1

Minor increase in O2 extraction from 75% to 90% Coronary blood flow rises in proportion to cardiac metabolic activity, through

the release of local vasodilator substances from the working myocardial cells

Briefly Discuss the Humoral factors that control Blood Pressure

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Systemic arterial pressure is controlled closely in order to maintain tissue perfusion. The mean arterial pressure (MAP) takes account of pulsatile blood flow in the arteries, and is the best measure of perfusion pressure to an organ.

MAP is defined: MAP = Diastolic arterial pressure + (pulse pressure / 3) where pulse pressure is the difference between systolic and diastolic arterial pressure.

MAP is the product of cardiac output (CO) and systemic vascular resistance (SVR): MAP = CO x SVR (Nb. CO = SV x HR and this could be substituted into the initial formula and then add discussion of

preload etc.) If cardiac output falls, for example when venous return decreases in hypovolaemia, MAP will also fall unless

there is a compensatory rise in SVR by vasoconstriction of the arterioles. This response is mediated by baroreceptors, which are specialised sensors of pressure located in the carotid

sinus and aortic arch, and connected to the vasomotor centre. A fall in blood pressure causes reduced stimulation of the baroreceptors, and consequent reduced discharge

from the baroreceptors to the vasomotor centre. This causes an increase in sympathetic discharge leading to the secretion of adrenaline, vasoconstriction,

increased heart rate and contractility. Conversely, rises in blood pressure stimulate the baroreceptors, which leads to increased parasympathetic

outflow to the heart via branches of the vagus nerve, causing slowing of the heart. There is also reduced sympathetic stimulation to the peripheral vessels causing vasodilatation.

Baroreceptor responses provide immediate control of blood pressure; if hypotension is prolonged, other mechanisms start to operate, such as the RAAS which leads to salt and water being retained in the circulation.

Preload, Afterload & Myocardial Contractility Cardiac Output = Stroke Volume x Heart

Rate For a 70kg man normal values are HR=70/min

and SV=70ml, giving a cardiac output of about 5 L min-1.

The cardiac index is the cardiac output per square metre of body surface area Normal values range from 2.5-4.0 L min-1 m-2.

Heart rate is determined by the rate of spontaneous depolarisation at the sinoatrial node (see above), but can be modified by the autonomic nervous system.

The vagus nerve acts on muscarinic receptors to slow the heart, whereas the cardiac sympathetic fibres stimulate beta-adrenergic receptors and increase heart rate.

Stroke Volume is determined by 3 major factors Preload, Afterload and Contractility In vivo, the preload is the degree to which the

myocardium is stretched before it contracts and the afterload is the resistance against which blood is expelled.

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Preload ContractilityAfterload

Stroke Volume

Intrathoracic pressureBlood volume

Posture

Sympathetic stimulationCatecholamines

Inotropes

SVRInotropes

Intrapericardial Pressure

Sympathetic Activity Catecholamines Parasympathe

tic Activity

Heart Rate

Cardiovascular Reflexes via sympathetic chain

(T1-T5)

ExerciseAnxietyTherapy

Cardiovascular Reflexes via the vagus nerves

Heart Rate Mechanisms of Excitation of the Heart by the

Sympathetic Nerves. Strong sympathetic stimulation can increase

the heart rate in young adult humans from the normal rate of 70 beats per minute up to 180 to 200 and, rarely, even 250 beats per minute.

Sympathetic stimulation increases the force of heart contraction to as much as double normal, thereby increasing the volume of blood pumped and increasing the ejection pressure.

Under normal conditions, the sympathetic nerve fibres to the heart discharge continuously at a slow rate that maintains pumping at about 30 per cent above that with no sympathetic stimulation.

Therefore, when the activity of the sympathetic nervous system is depressed below normal, this decreases both heart rate and strength of ventricular muscle contraction, thereby decreasing the level of cardiac pumping as much as 30 per cent below normal

Parasympathetic (Vagal) Stimulation of the Heart. Strong stimulation of the parasympathetic

nerve fibres in the vagus nerves to the heart can stop the heartbeat for a few seconds, but then the heart usually “escapes” and beats at a rate of 20 to 40 beats per minute as long as the parasympathetic stimulation continues.

In addition, strong vagal stimulation can decrease the strength of heart muscle contraction by 20 to 30 per cent.

The vagal fibres are distributed mainly to the atria and not much to the ventricles, where the power contraction of the heart occurs. This explains the effect of vagal stimulation mainly to decrease heart rate rather than to decrease greatly the strength of heart contraction.

Nevertheless, the great decrease in heart rate combined with a slight decrease in heart contraction strength can decrease ventricular pumping 50 per cent or more.

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Preload Ventricular Preload:

Physiological Definition: Pre-systolic length of cardiac muscle fibres

Physiological index: Left Ventricular End-Diastolic Volume

Practical Concept: the ventricular load at the end of diastole, before contraction has started

Practical index: CVP or PCWP Factors affecting Preload:

Total blood volume Posture Intrathoracic and intrapericardial

pressures Venous tone and compliance Pumping action of skeletal muscle Synchronous atrial contribution to

ventricular filling Ventricular end-diastolic compliance

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Afterload Afterload

Physiological Definition : Ventricular wall stress developed during systole

Physiological Index: Systolic ventricular wall stress Practical concept: Impedance to Ejection of blood from the heart into

the circulation Practical Index: MPAP, or MAP Factors which affect Afterload:

SVR or PVR Factors stimulating or depressing cardiac contraction Intrathoracic and Intrapericardial pressure Preload Ventricular wall thickness

By applying Laplace's law, increased LV wall thickness will decrease wall stress despite the necessary increase in LV pressure to overcome the aortic stenosis

Ventricular size In a failing heart, the radius of the LV increases, thus increasing wall stress

Aortic compliance is an additional determinant of afterload Aortic compliance is the ability of the aorta to give way to systolic forces from

the ventricle. Changes in the aortic wall (dilation or stiffness) can alter aortic compliance and thus afterload.

Examples of pathologic conditions that alter afterload are aortic stenosis and chronic hypertension. Both impede ventricular ejection, thereby increasing afterload.

Wall stress and heart rate are probably the two most relevant indices that account for changes in myocardial oxygen demand.

• Law of Laplace• T =Pr/W

This law states that tension in the wall of a cylinder (T) is equal to the product of the transmural pressure (P) and the radius (r) divided by the wall thickness (w):

•SVR= 80 x (MAP - CVP)/CO•Normal 900-1500 dyne∙s∙cm-5

•PVR= 80 x (PAP-LAP)/CO•Normal 90-150 dyne∙s∙cm-5

Contractility Contractility

Physiological Definition : Systolic myocardial work done with a given preload and afterload

Physiological Index: Ventricular Stroke Work Stoke Work = SV x P Normalised to BSA by using SI VSWI Normal LVSWI =45-60 g.mm-2

Practical Concept: Ejection fraction for given CVP and MAP

Practical index: Ejection Fraction Altered by: Factors that modify contractility will create

a family of Frank-Starling curves with different contractility Serum calcium levels Autonomic Nervous System Inotropes Myocardial ischaemia or infarction Hypoxia Acidosis Mismatched ventriculoarterial coupling

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236.1100

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mmgSILAPMAPLVSWI

Draw the Pressure volume loop for a left ventricle in a normal adult. Outline what information can be obtained from such a loop Demonstrates the sequential dynamic changes in

a single cardiac cycle- (time not considered) A-B: Phase I: Diastolic filling: MV opens at A closes

at B. The initial P (A-B) despite V, due to ing ventricular relaxation and distensibility Small pressure rise prior to B is due to atrial contraction

contributing to Vent filling B-C: Phase II: Isovolumic contraction P but stable

V C- D: Phase III: Ejection Phase: AV opens at C; Large

V mild P The V is followed by a P due to ejection

D-A: Phase IV: AV Closes isovolumic relaxation Sharp P and stable V

Slope on Diastolic curve is the LV elastance 1/Compliance: Fairly flat but slowly curves up : as ventricle is easy to fill: but hard to overfill

The area inside the loop represents the external work performed by the LV for that cardiac cycle

C represents Diastolic BP Slope of ESPVR line represents and index of

contractility. Steeper = contractility Slope of ESP-EDV Line is an index of afterload

31

Filling

Contraction

Ejection

Relaxation

ESV

ESPVR Line

ESP-EDV Line

Pressure Volume Loops under different conditions Preload Phase II

shift to right: Preload:- The point on

the X axis which represents end-diastole is the best index of preload

LVEDP is less reliable index of preload due to changes in compliance, especially if LV Distended

32

Pressure Volume Loops under different conditions

Afterload (e.g. AS) Phase III shift Upwards.

The best index of afterload is the slope of the straight line connecting the LVEDV with the end systolic point on the loop (Point D).

Afterload:- LV wall tension required to overcome impedance to ejection of blood in arterial circulation

33

The afterload line for loop 2 makes a larger angle with the x axis its afterload is higher

Pressure Volume Loops under different conditions contractility

(adrenaline Inf) Phase IV shifts to left;

The best index of contractility is slope of end-systolic PV line.

representing an increased work performed in ejecting an increased stroke volume need to know end-

systolic elastance point34

Quote Starlings Law of the Heart. Basically,this law states that when increased quantities of blood flow

into the heart, the increased blood stretches the walls of the heart chambers.

As a result of the stretch, the cardiac muscle contracts with increased force, and this empties the extra blood that has entered from the systemic circulation.

Therefore, the blood that flows into the heart is automatically pumped without delay into the aorta and flows again through the circulation

Refers to intrinsic capacity of heart to control SV, responding with greater force of contraction to the stimulus of increased diastolic stretch produced by extra venous return heterometric regulation

When an extra amount of blood flows into the ventricles, the cardiac muscle itself is stretched to greater length. This in turn causes the muscle to contract with increased force because the actin and myosin filaments are brought to a more nearly optimal degree of overlap for force generation. Therefore, the ventricle, because of its increased pumping, automatically pumps the extra blood into the arteries

In the human heart, maximal force is generated with an initial sarcomere length of 2.2 micrometres, a length which is rarely exceeded in the normal heart. Initial lengths larger or smaller than this optimal value will drop the force of the muscle owing to less overlap of the thin and thick filaments for larger values and more overlap of the thin filaments for smaller values.

The above is true of healthy myocardium

35

Outline the factors that determine the RVEDV

36

EDV is the volume of blood in a ventricle at the end of filling (diastole) ≡ Preload. An increase in EDV increases the preload on the heart and, through the Frank-Starling mechanism of the heart,

increases the amount of blood ejected from the ventricle during systole (stroke volume). Ventricular Filling is influenced by a variety of factors

Venous return The most important determinant of RVEDV is venous return In the absence of significant pulmonary/RV dysfunction venous return is also the major determinant of LVEDV Because nearly two-thirds of the blood in the systemic circulation is stored in the venous system, end-diastolic volume is closely related

to venous compliance. Blood Volume:

Acute haemorrhage activation of the baroreceptor reflex venoconstriction venous compliance venous return, EDV Distribution of blood volume

Posture: Standing venous return Muscular activity venous return as a result of the pumping action of skeletal muscle

Intrathoracic pressure: venous return with inspiration as –ve intrathoracic pressure pressure gradient along which blood flows to heart the opposite is also true

Pericardial pressure: intrapericardial pressure limits the extent to which the ventricle can fill as does ventricular compliance

Venous tone: venous compliance elevates the capacitance of the veins, reducing venous return and therefore end-diastolic volume. Decreasing venous

compliance has the opposite effect. Rhythm

Absent (fibrillation), ineffective (flutter) or low/altered (junctional rhythms) timing of atrial contraction ventricular filling by 20-30% as Atrial contractions aid ventricular filling

Rate HR length of diastole ventricular filling at high rates

Explain the effects of intermittent positive pressure ventilation on left ventricular output IPPV and Peep causes a progressive decrease in

CO 10% IPPV + PEEP 18% IPPV + 9 cmH2O Peep 36% IPPV + 16 cmH2O Peep

Consensus Intrathoracic Pressure obstruction of RA filling Normally, with spontaneous respiration, the negative

Intrathoracic pressure during inspiration draws blood into the chest from major veins (thoracic pump)

Positive intrathoracic pressure abolishes this effect and also imposes further reduction in driving pressure for flow between extra- and intrathoracic vessels

RV filling pressures LV filling CO Furthermore

IPPV + Peep Lung volumes PVR RV Emptying L Deviation of Interventricular septum LV filling and compliance CO

37

The systemic circulation

38

The systemic blood vessels are divided into arteries, arterioles, capillaries and veins. Arteries supply blood to the organs at high pressure, whereas arterioles are smaller vessels with muscular walls

which allow direct control of flow through each capillary bed. Capillaries consist of a single layer of endothelial cells, and the thin walls allow exchange of nutrients between blood

and tissue. Veins return blood from the capillary beds to the heart, and contain 70% of the circulating blood volume, in contrast

to the 15% in the arterial system. Veins act a reservoir, and venous tone is important in maintaining the return of blood to the heart, for example in

severe haemorrhage, when sympathetic stimulation causes venoconstriction. Blood flow

The relationship between flow and driving pressure is given by the Hagen-Poisseuille formula. This states that flow rate in a tube is proportional to: Driving pressure x Radius4

Length x Viscosity In blood vessels flow is pulsatile rather than continuous, and viscosity varies with flow rate, so the formula is not

strictly applicable, but it illustrates an important point; small changes in radius result in large changes in flow rate. In both arterioles and capillaries changes in flow rate are brought about by changes in tone and therefore vessel radius.

Viscosity describes the tendency of a fluid to resist flow. At low flow rates the red blood cells stick together, increasing viscosity, and remain in the centre of the vessel. The blood closest to the vessel wall (which supplies side branches) therefore has a lower haematocrit. This process is known as plasma skimming. Viscosity is reduced in the presence of anaemia, and the resulting increased flow rate helps maintain oxygen delivery to the tissues.   

Control of the systemic circulation Arteriolar tone determines blood flow to the capillary beds. A number of

factors influence arteriolar tone, including autonomic control, circulating hormones, endothelium derived factors and the local concentration of metabolites.

Autonomic control is largely by the sympathetic nervous system, which supplies all vessels except capillaries. Sympathetic fibres arise from the thoracic and lumbar segments of the spinal cord. These are under the control of the vasomotor centre in the medulla, which has distinct vasoconstrictor and vasodilator areas.

Although there is a baseline sympathetic discharge to maintain vascular tone, increased stimulation affects some organs more than others (Figure 4).

This tends to redistribute blood from skin, muscle and gut to brain, heart and kidney.

Increased sympathetic discharge is one of the responses to hypovolaemia, for example in severe blood loss, with the effect of protecting blood supply to the vital organs. The predominant sympathetic influence is vasoconstriction via alpha-adrenergic receptors.

However, the sympathetic system also causes vasodilatation via beta adrenergic and cholinergic receptor stimulation, but only in skeletal muscle. This increased blood flow to muscle is an important part of the "fight or flight"

reaction, when exercise is anticipated.

39

Control of the systemic circulation II Circulating hormones such as adrenaline and angiotensin II are potent

vasoconstrictors, but they probably have little effect on acute cardiovascular control.

In contrast, endothelium derived factors play an important role in controlling local blood flow.

These substances are either produced or modified in the vascular endothelium, and include prostacyclin and nitric oxide, both potent vasodilators.

An accumulation of metabolites such as CO2, K+, H+, adenosine and lactate causes vasodilatation.

This response is probably an important mechanism of autoregulation, the process whereby blood flow through an organ is controlled locally, and remains constant over a wide range of perfusion pressure.

Autoregulation is a particular feature of the cerebral and renal circulations. 

40

Describe the substances released by the endothelium. Explain the role they play in regulating blood flow through the peripheral circulation Substances released by the endothelium can be divided into

either Vasoconstrictors or Vasodilators Vasoconstrictors

Endothelins -1, a large 21 amino acid peptides requires only nanogram quantities to cause powerful

vasoconstriction. This substance is present in the endothelial cells of all or most blood

vessels. The usual stimulus for release is damage to the endothelium, such

as that caused by crushing the tissues or injecting a traumatizing chemical into the blood vessel.

After severe blood vessel damage, release of local endothelin and subsequent vasoconstriction helps to prevent extensive bleeding from arteries as large as 5 mm in diameter that might have been torn open by crushing injury

Two different endothelin receptors have been cloned, both of which are coupled via G proteins to phospholipase C.

The ETA receptor, which is specific for endothelin-1, is found in many tissues and mediates the vasoconstriction produced by endothelin-1.

The ETB receptor responds to all three endothelins, and is coupled to Gi. It may mediate vasodilation, and it appears to mediate the developmental effects of the endothelins.

Endothelin-1 is not stored in secretory granules, and most regulatory factors alter the transcription of its gene, with changes in secretion occurring promptly thereafter.

41

Describe the substances released by the endothelium. Explain the role they play in regulating blood flow through the peripheral circulation

42

Vasodilators Nitric Oxide

Synthesised From arginine by the action of Nitric Oxide Synthase 3 in the endothelium

The NO that is formed in the endothelium diffuses to vascular smooth muscle cells where it activates soluble guanylyl cyclase, producing cGMP which in turn mediates the relaxation of the vascular smooth muscle

NOS is activated by agents that cause an increase in intracellular Ca2+, including Ach, bradykinin, Substance P, histamine, serotonin and sheer stress acting on the cell membrane

Prostacyclin Produced in endothelium from

arachidonic acid by the actions of prostacyclin synthase enzyme.

PGI2 is released by the endothelium and binds to a IP receptor on surface of vascular smooth muscle

As a Gs -GPRL it acts by increasing intracellular cAMP; cAMP inactivates myosin light-chain kinase and facilitates Ca2+ efflux,.

Its release is stimulated by the same factors that stimulate NO release

T1/2 6 minutes

Draw both aortic root and radial artery pressure wave forms on the same axes. Explain the differences between them Radial Curve has a delayed onset because

of time taken to travel distally Distorted shape (due to reflection,

resonance, transmission velocities, arterial tapering) Taller: higher systolic pressure Narrower at its peak: higher velocity of the

high pressure peak Does not have an incisura due to dampening

of high pressure components by viscoelastic properties of arterial walls

Diastolic Hump due to reflection and resonance

These changes diminish with age with radial curve resembling Aortic curve more with age

Taller and narrower means both the upstroke and downstroke are steeper

Radial pulse pressure is higher but the Radial MAP is not different from central MAP

43

Explain the significance of plasma oncotic pressure in capillary fluid dynamics Defn:- Oncotic Pressure is the plasma osmotic pressure due to the proteins and other colloids

too large (>30kD) to cross the capillary membrane Albumin constitutes ~70% Normal is 25 mm Hg ~0.5% of total Plasma osmotic pressure- but very important in capillary

fluid dynamics (starling forces) where the protein-impermeable capillary membranes allow it to maintain intravascular volume by balancing opposing plasma hydrostatic pressure as well as the interstitial oncotic and hydrostatic pressures

Starlings Hypothesis:- Filtration of fluid across the capillary wall is dependent on the balance between hydrostatic pressure gradient and the oncotic pressure gradient across the capillary. Fluid Movement = k x Net Driving Pressure= hydrostatic pressure gradient – oncotic pressure gradient = k{(Pc -Pi) - (c- i)}

k = filtration coefficient ( area X hydraulic conductivity) = reflection coefficient (relative impediment to the passage of substance through capillary wall) Pc =Capillary Hydrostatic Pressure Pi = Interstitial Hydrostatic Pressure c = Capillary Oncotic Pressure I = Interstitial Oncotic Pressure

The interstitial fluid pressure varies from one organ to another, and there is considerable evidence that it is subatmospheric (about –2 mm Hg) in subcutaneous tissue. It is, however, positive in the liver and kidneys and as high as 6 mm Hg in the brain. The other force is the osmotic pressure gradient across the capillary wall (colloid osmotic pressure of plasma minus colloid osmotic pressure of interstitial fluid). This component is directed inward

Starling pointed out that under normal conditions, a state of near equilibrium exists at the capillary membrane, where the amount of fluid filtering outwards from some capillaries, almost equals the quantity of fluid returned to the system by reabsorption through other capillaries

The slight disequilibrium that does occur accounts for the small amount of fluid that is eventually returned by way of the lymphatics

44

Explain the significance of plasma oncotic pressure in capillary fluid dynamics

45

The average capillary pressure at the arterial end is 15-25 mmHg greater than the venous ends.

Because of this difference, fluid filters out of the capillaries at the arterial ends and is reabsorbed back into the capillaries at the venous end

Thus a small amount of fluid actually flows though the tissues from the arterial end to the venous end

When you look at the mean forces in the capillaries the net outward force is 0.3mmHg

This results in a net fluid flux is 20 ml/min at the arterial end with 18ml/min returned at the venous end 2ml/min (10%) entering the ISF This needs to be removed otherwise the tissues would become congested

Lymph Calculated oncotic pressure is 15 but actual pressure is 28 due to

Gibbs-Donnan effect (9mmHg) Due to positively charged cations that bind to the negatively charged plasma

proteins Excluded volume effect (4 mmHg)

Due to effect of proteins which have leaked into the interstitial fluid Clinically evident oedema does not appear until the oncotic pressure has

decreased below 11mmHg (albumin 20g/L) When albumin levels are low, factors that protect against oedema are: Increased lymph flow Increased interstitial tissue hydrostatic pressure with increased volume Decreased interstitial protein and oncotic pressure

Give and account of the Starlings forces within the capillary circulation. Include specific reference to the pulmonary and glomerular capillaries I

46

Glomerulus GFR= Hydraulic permeability x surface area x Net Filtration Pressure Starling forces account for the NFP component of GFR

GFR = kf x {(Pc - Pi) - (πc - πi)} k = filtration coefficient ( area X hydraulic permeability) = reflection coefficient ~1.0 Pc =Capillary Hydrostatic Pressure: Afferent= 60; Efferent = 58 Pi = Interstitial Hydrostatic Pressure: Afferent= 15; Efferent = 15 π c = Capillary Oncotic Pressure : Afferent= 21; Efferent = 33 π I = Interstitial Oncotic Pressure = 0 NFP = Afferent= 24; Efferent = 10 filtration along whole length GFR = 125ml/min =20% of plasma is normally filtered as blood passes through the glomerulus

The filtration coefficient is high because of the high water permeability The reflection coefficient is high because the glomerular capillaries are impermeable to proteins Hydrostatic pressure is high along the whole length due to large loss of fluid and impermeability

to proteins The oncotic pressure in the capillary increases along its length and is important for reabsorption

in proximal tubule, with net filtration along whole length of capillary Hydrostatic pressure in the glomerular capillaries is affected by the balance between afferent and

efferent arteriolar constriction

Give and account of the Starlings forces within the capillary circulation. Include specific reference to the pulmonary and glomerular capillaries Cont Pulmonary

Q= kf x {(Pc - Pi) - (πc - πi)} Kf = filtration coefficient

related to effective surface area per mass of tissue

= ~0.5 expresses permeability of capillaries to albumin

Pc = 0 to 15 mean 7 Varies with vertical height due to effect of

gravity Pi = variable but ranges from zero to slightly

negative: norm -4 to -8 Effectively equal to alveolar pressure in the

alveolar walls π c = Afferent= 28; Efferent = 28

Same as systemic circulation π I = Interstitial Oncotic Pressure = 14:

pulmonary endothelium is partially permeable to albumin albumin conc ~1/2 of plasma

Estimated from lung lymph NFP = (7 - -4) – 0.5(28 -14) = 11 – 7 = 4

The balance of forces is toward reabsorption

The net amount of fluid removed is 10-20ml/h which is rapidly removed by the pulmonary lymphatics and returned to the central circulation

The capillary hydrostatic pressure is lower because of the generally lower pressure in the pulmonary artery

The interstitial oncotic pressure is high indicating significant leak of protein across the thin capillary wall under normal circumstances. The reflection coefficient is therefore low ~0.5

The capillaries are called intra-alveolar vessels as the pressure they are exposed to is close to alveolar pressure ( mean = 0) However, actual measurements of the pressure in the alveolar interstitium have found slightly negative pressures (~-2 mmHg). Closer to the hilum, the interstitial pressures become more negative and this favours the flow from alveolar interstitium into the pulmonary lymphatics

NFP is small but favours reabsorption

47

Briefly Discuss the factors that influence the rate of blood flow through a capillary Bed There is an inverse relationship between velocity and cross

sectional area. The capillaries have the maximal cross sectional area and

minimal flow rate cross sectional area of aorta = 2.5 cm2 cross sectional area of capillaries =2500 cm2 capillaries have a flow ~1/1000 th of velocity of flow in aorta

Many capillaries arise from each arteriole so that the total cross-sectional area of the capillary bed is large despite the fact that the cross-sectional area of each capillary is less than the arteriole. As a result, blood flow velocity becomes quite slow in the capillaries.

Transit time from the arterial to the venous end is ~1-2 sec Capillary pressures: Norm 32 mmHg arterial and 15 venous The capillary pulse pressure ~5 mmHg arterial end and 0

mmHg venous end

48

Discuss the relationship between vascular tone and tissue oxygenation

49

Tissue metabolic activity is the main regulator in local regulation of blood flow According to the metabolic mechanism, any intervention that results in an O2 supply that

is inadequate for the requirements of the tissue gives rise to the formation of vasodilator metabolites

These are released locally and act to dilate the resistant vessels When the metabolic rate of the tissue increases or the O2 delivery to the tissue decreases,

more vasodilator substance is released and the metabolic concentration in the tissue increases.

The exact nature of the Vasodilator is unknown ?? Adenosine/ NO/electrolyte/PO2/ or a combination of all/any

Metabolic control of vascular resistance by the release of a vasodilator is predicated on the existence of basal vascular tone.

Basal tone is independent of nervous system- unknown factor An expression of myogenic activity in response to the stretch imposed by blood pressure High O2 tension of arterial blood Ca2+ ions Unknown factor

Should add that this is true for systemic circulation only as the Pulmonary circulation is the opposite due to hypoxic vasoconstriction.

Intrinsic (Local) Regulation of Peripheral Blood Flow

50

Autoregulation: Intrinsic ability of an organ to maintain constant blood flow despite changes in perfusion pressure

Two main Mechanisms Myogenic Mechanism

The vascular smooth muscle contracts in response to an increase in transmural pressure stretch and relaxes in response to a decrease in transmural pressure

Metabolic Mechanism Any intervention that results in and inadequate O2 supply for the requirements of the tissue

give rise to the formation of vasodilator metabolites (NO) The metabolites released from the tissue act locally to dilate the resistance vessels

Active hyperaemia: increased blood flow caused by enhanced tissue activity (osmolarity, K+, P+, adenosine, NO)

Metabolic control of vascular resistance by the release of a vasodilator substance is predicated by the presence of basal vessel tone, independent of nervous system

Basal tone may be due to Expression of myogenic activity in response to stretch imposed by BP High O2 Tension of arterial blood Ca2+ Unknown factor

Extrinsic Regulation of Peripheral Blood Flow Mainly mediated by SNS Pressor Region

Dorsal Lateral Medulla Stimulation causes vasoconstriction; cardiac acceleration & enhanced

myocardial contractility Depressor Area

Caudal and Ventromedial to Pressor region Stimulation causes decreased BP

Direct spinal inhibition and Inhibition of medullary Pressor Region

Pressor area fibres descend in spinal cord & synapse at different levels of thoracolumbar region (T1-L3) ventral roots to paravertebral sympathetic chains ganglia peripheral nerves follow large arteries network of fibres around resistance & capacitance vessels

Vasoconstrictor region is tonically active reflexes or humoral stimulation of Pressor region firing Norad release

receptor vasoconstriction Inhibition of pressor area tonic activity vasodilatation

Vasoconstrictor fibres supply arteries, arterioles & veins Neural influence on large vessel of far less functional importance Capacitance vessels more responsive to SNS than resistance vessels

51

Describe the role of Baroreceptors in the control of systemic arterial pressure I Baroreceptors are very important in short-term control of arterial pressure.

Activation of the reflex allows for rapid adjustments in blood pressure in response to abrupt changes in blood volume, cardiac output, or peripheral resistance during exercise.

Baroreceptors are irregularly branched and coiled nerve endings located in the walls of the heart and major vessels High pressure receptors in Carotid sinus and Aorta Low Pressure receptors in Atria and pulmonary vessels

Carotid baroreceptors send afferent signals to circulatory brainstem centres via Herring's nerve (branch of glossopharyngeal), while aortic baroreceptor afferent signal travels along the vagus nerve

They respond to the degree of stretch in the vessel or heart wall and hence to the stretch (actually transmural pressure) in the vessel or heart

After the baroreceptor signals have entered the NTS of the medulla, secondary signals inhibit the vasoconstrictor centre of the medulla and excite the vagal parasympathetic centre. The net effects are (1) vasodilation of the veins and arterioles throughout the peripheral circulatory

system and (2) decreased heart rate and strength of heart contraction. Therefore, excitation of the baroreceptors by high pressure in the arteries reflexly

causes the arterial pressure to decrease because of both a decrease in peripheral resistance and a decrease in cardiac output.

Conversely, low pressure has opposite effects, reflexly causing the pressure to rise back toward normal.

The baroreceptor response curve is sigmoidal with a linear segment between pressures of 80-180 mm Hg

Adaptation to acute blood pressure changes occurs over the course of 1-2 days, making this reflex ineffective for long-term blood pressure control Curve shifts to the right

52

Describe the role of Baroreceptors in the control of systemic arterial pressure II Carotid and Aortic Baroreceptor

reflex The baroreceptors in the carotid sinus

and aortic arch monitor arterial pressure, arterial pulse pressure and heart rate

a primary purpose of the arterial baroreceptor system is to reduce the minute by minute variation in arterial pressure to about one third that which would occur were the baroreceptor system not present.

Carotid sinus baroreceptors are more sensitive to blood pressure changes than the aortic arch They also respond to mechanical

stimulation, which increases their firing rate inhibitory response used in SVT

Cardiopulmonary baroreceptor reflex The stretch receptors in the atria, ventricle

and pulmonary vessel protect against rapid changes in intravascular volume by varying tonic discharge inhibitory response

They also play a role in controlling heart rate

Two types of stretch receptors in the atria Type A: discharge predominately during atrial

systole Type B: discharge predominately during atrial

filling, particularly over the latter part of diastole

When intravascular volume expands atrial filling is increases and both type A and B receptors are stimulated vagus nerve inhibition of medullary pressor centre & sympathetic stimulation of sinus node vasodilation, fall in BP, increase in renal blood flow & increased urine output and a rise in heart rate

53

The Bainbridge Reflex

54

An increase in atrial pressure also causes an increase in heart rate, sometimes increasing the heart rate as much as 75 per cent.

A small part of this increase is caused by a direct effect of the increased atrial volume to stretch the sinus node: direct stretch can increase the heart rate as much as 15 per cent.

An additional 40 to 60 per cent increase in rate is caused by a nervous reflex called the Bainbridge reflex. The stretch receptors of the atria that elicit the Bainbridge reflex transmit their afferent signals through the vagus nerves to the medulla of the brain.

Then efferent limb consists of sympathetic nerves to sinus node increase heart rate and strength of heart contraction.

Thus, this reflex helps prevent damming of blood in the veins, atria, and pulmonary circulation.

Explain the cardiovascular responses to a valsalva manoeuvre maintained for 30 seconds. What can be learnt about CV FNS from observing these responses The normal physiological response consists of 4 phases, which

are marked on the figure at right: Phase 1

Initial pressure rise: On application of expiratory force, pressure rises inside the chest forcing blood out of the pulmonary circulation into the left atrium. This causes a mild rise in blood pressure.

Phase 2 Reduced venous return and compensation: Return of blood to the

heart is impeded by the pressure inside the chest. The output of the heart is reduced, the blood pressure falls. This occurs from 5 to about 14 seconds in the illustration. The fall in blood pressure reflexly causes blood vessels to constrict with some rise in pressure (15 to 20 seconds). This compensation can be quite marked with pressure returning to near or even above normal, but the cardiac output and blood flow to the body remains low. During this time the pulse rate increases.

Phase 3 Pressure release: The pressure on the chest is released, allowing the

pulmonary vessels and the aorta to re-expand causing a further initial slight fall in pressure (20 to 23 seconds) due to decreased left ventricular return and increased aortic volume, respectively. Venous blood can once more enter the chest and the heart, cardiac output begins to increase.

Phase 4 Return of cardiac output: Blood return to the heart is enhanced by the

effect of entry of blood which had been dammed back, causing a rapid increase in cardiac output and of blood pressure (24 seconds on). The pressure usually rises above normal before returning to a normal level. With return of blood pressure, the pulse rate returns towards normal.

Deviation from this response pattern signifies either abnormal heart function or abnormal autonomic nervous control of the heart.

55

Explain the cardiovascular responses to a valsalva manoeuvre maintained for 30 sec. What can be learnt about CV FNS from observing these responses CONT In CCF with LVEF less than 0.3 and LVEDP

35mmHg, there may be no decrease in BP in phase 2 ( pulmonary reserve, VR and MAP do not airway pressure) and no BP with release of straining. This is the Abnormal Square Wave response

If Beta-blocked: phase 1 would still arise and would still get vagal mediated HR but less phase 2 HR and less phase 4 overshoot in BP due to less prior SNS compensation in phase 3

Ganglion block/spinal anaesthetic (autonomic neuropathy): Lower BP in phase 2 (CO not followed by SNS mediated in SVR by BR) and normal overshoot is replaced by a slow recovery of arterial pressure as CO returns to control values. HR stays the same throughout

Alpha-Blocked: Lower BP during phase 2 and increased overshoot in phase 4; chase mechanism

56

Arterial blood pressure response and Korotkoff's sounds during Valsalva's manoeuvre.

 (A) Sinusoidal response in normal patient.

 (B) Absent overshoot in patient with autonomic dysfunction.

 (C) Square wave response in patient with heart failure.

The Valsalva manoeuvre is a useful bedside test of autonomic function.  With autonomic dysfunction (e.g. autonomic neuropathy and drugs), the BP falls and remains low until the intrathoracic pressure is released.  The changes in pulse rate and overshoot are absent. 

Explain the cardiovascular responses to a valsalva manouevre maintained for 30 sec. What can be learnt about CV FNS from observing these responses CONT

57

Clinical uses of Valsalva manoeuvre: Reversion of SVT- based on reflex increased

vagal activity during phase 4 Testing autonomic Function Aid in the assessment of some heart murmurs

HOCM and MV prolapse increase while all others decrease in loudness

Describe the Autonomic Innervation of the Heart and the direct effect of autonomic stimulation on the heart.

58

Parasympathetic Pathways Originate in medulla oblongata, in cells that lie in the dorsal motor nucleus of the Vagus:

Nucleus ambiguus Pass inferiorly through neck as the cervical vagus nerves, which lie close to the common carotid

arteries Pass through the mediastinum to synapse with post-ganglionic cells on the epicardial surface or

within the heart wall itself. PNS fibres primarily innervate the atria and conducting tissues Acetylcholine acts on specific cardiac muscarinic receptors (M2) to produce negative

chronotropic, dromotropic, and ionotropic Right vagus inhibits SA Node; Left vagus inhibits AV conduction; there is some cross over Both SA and AV nodes are rich in cholinesterase short effect due to rapid hydrolysis Effect of vagal activity on SA & AV nodal function has a very short latency (50-100 ms) ∵ the

release cholinesterase activates special K+ channels in the cardiac cells When the vagus nerve is stimulated at a constant frequency for several seconds, the HR

abruptly and attains a steady state within one-two cardiac cycles. When stimulation is discontinued, the HR returns quickly to its basal level.

The combination of the brief latency and rapid decay if the response provides the opportunity for the vagus nerves to exert a beat by beat control of SA and AV nodal fns

PNS preponderate over SNS effect at the SA Node

Describe the Autonomic Innervation of the Heart and the direct effect of autonomic stimulation on the heart CONT

59

Sympathetic Pathways Originate in thoracic spinal cord T1-4, travel to heart initially through the stellate ganglia then as

the cardiac nerves The post-ganglionic sympathetic fibres approach the base of the heart along the adventitial

surface of the great vessels On reaching the heart these fibres are distributed to the various chambers as an extensive

epicardial plexus and penetrate the myocardium along the coronary vessels- split into R & L divisions

Noradrenaline release causes positive chronotropic, dromotropic and ionotropic effects Predominately via β1 receptors; β2 receptors are fewer in number, mainly in atria HR α1 have a positive ionotropic effect Sympathetic influences have gradual onset for 2 reasons

Response to SNS depends mainly on intracellular build-up of a secondary messenger (cAMP) in the automatic cells of the SA node

The neurotransmitters are released at different rates from the post ganglionic nerve endings of the two autonomic divisions: Enough Ach can be released in a brief period to stop the heartbeat entirely; Conversely, only enough NAd is released during each cardiac cycle to change cardiac behaviour by only a small increment

NAd has a significantly longer half life so the effects of sympathetic stimulation decay very gradually after the cessation of stimulation, in contrast to the abrupt termination of the response after vagal stimulation

Skeletal Muscle Circulation Rate of blood flow varies directly with

the contractile activity of the tissue and the type of tissue

Blood flow and capillary density greater in Red (slow twitch, high-oxidative muscle) than White (fast twitch, low-oxidative)

Resting Muscle Precapillary arterioles exhibit

asynchronous intermittent contractions & relaxations large % of capillary bed not perfused at any one time

Low flow in Resting muscle = ~1.4 – 4.5 ml∙ 100g-1∙min-1

With exercise the resistance vessels relax and muscle flow increase many fold (15-20 times resting level)

60

Skeletal Muscle Circulation Regulation Physical Factors

As with all tissues; physical factors influence muscle blood flow ABP Tissue pressure Blood viscosity

During exercise another physical factor comes into play Squeezing effect of active muscle on

vessels With intermittent contractions

Inflow restricted Outflow enhanced

Venous valves prevents backflow of blood into veins between contractions aids forward propulsion of blood

With strong sustained contractions the vascular bed can be compressed to a point where flow ceases

61

Skeletal Muscle Circulation Regulation Cont Neural Factors

Resistance vessels of muscle possess high basal tone Also, low-frequency activity in sympathetic

vasoconstrictor nerve fibres Basal rate quite low ≈ 1-2/sec Max vasoconstriction seen with low rate of 8-10/sec Vasoconstriction results from release of NA at nerve ending

Tonic activity of SNS is greatly influenced by reflexes from baroreceptors Carotid sinus pressure vasodilatation of muscle vascular

bed via inhibition of sympathetic vascular activity Carotid sinus pressure vasoconstriction of muscle

vascular bed Because muscle represents the largest vascular bed, the

participation of its resistance vessels in vascular reflexes plays an important role in maintaining a constant ABP

Local Factors Dissection of the sympathetic nerves to the muscle

abolishes the neural component of vascular tone and unmasks the intrinsic basal tone of the blood vessels

Neural and Local blood flow regulatory mechanisms oppose each other & during muscle contraction the local vasodilatation mechanism supervenes

However, during strong exercise the strong sympathetic nervous stimulation slightly reduces the vasodilatation induced by locally produced metabolites

62

Cutaneous (Skin) Circulation

63

O2 & nutrient requirements are low unlike most other body tissues; the supply of these essential nutrients is not the chief governing factor regulating the cutaneous blood flow

The primary fns of the cutaneous circulation is maintenance of a constant body temperature

the skin shows wide fluctuations in blood flow, depending on need to lose or conserve body heat

Skin colour depends on the volume and flow of blood in the skin & the amount of O2 bound to Hb Colour by pigment but pallor/ruddiness is mainly a function of the amount of blood in the skin

Two types of resistance vessels Arteriovenous anastomoses

Shunt blood from arterioles to venules and venous plexuses bypass capillary bed Primarily located in fingertips, toes, palms, soles, ears, nose lips Almost exclusively under SNS control

Maximally dilated when nerve supply interrupted SNS stimulation can lead to vasoconstriction to the point of obliteration of the lumen

No obvious metabolic control Fail to show reactive hyperaemia or autoregulation of blood The regulation of blood flow through anastomotic channels is governed principally by the SNS in response to

reflex activation by temperature receptors or from higher centres of the nervous system

Cutaneous Circulation Regulation

64

Arterioles Similar to those found elsewhere in body Exhibit some basal tone and under dual control of SNS and Local Regulatory Factors

Neural control more important than local control Adrenaline/Noradrenaline only elicit vasoconstriction PNS vasodilatory nerve fibres do not innervate skin BV However, SNS of sweat glands release of bradykinin local vasodilatation

of arterioles Skin vessels of certain regions are under the influence of higher centres of

CNS Blushing with embarrassment/anger (inhibition) Blanching with anxiety/fear (stimulation) Head; Neck; Shoulders; Chest

Arterioles show signs of autoregulation & reactive hyperaemia Eg flushing when BP cuff deflated Autoregulation best explained by myogenic mechanism

Cutaneous Circulation Regulation Cont

65

Ambient & Body Temperature play an important role in the regulation of skin blood flow ∵ primary skin fns is to protect body from adverse changes in the

environment & ambient temperature is one of the most important external variables the body has to deal with

Cold vasoconstriction controlled by temperature regulatory centre of hypothalamus (SNS) Prolonged exposure to severe cold 2ry vasodilatation Seen as rosy cheeks of people in cold environment Red colour of slow flowing blood ∵ reduced O2 uptake by cold skin & cold

induced left shift of O2 dissociation curve Heat vasodilatation

Local vasodilatation of resistance and Capacitance vessels and AV anastomosis independent of the vascular nerve supply

Also get reflex dilatation of other areas which is a combination of Ant hypothalamic stimulation by the returning of warmed blood and stimulation of receptors in the heated area

Close proximity of major arteries and vein permits considerable heat exchange (counter current) decrease temperature fluctuations

Explain in physiological terms the effect of severe aortic stenosis on myocardial supply and demand (July08: 45%)

66

Aortic stenosis is the abnormal narrowing of the aortic valve, which restricts the flow of blood from the ventricle into the aorta Considered severe if the systolic gradient exceeds 50 mm Hg or effective AVA <0.8cm2

AS causes pressure overload on the LV Compensatory hypertrophy to reduce the wall tension follows

Law of Laplace Wall tension =Pr/2T

This leads to decreased LV compliance and requires high LVEDP (& LA pressure) for filling Gross imbalance between oxygen supply and demand is due to

the increased demand of pressure load and muscle hypertrophy versus

a decreased supply of myocardial oxygen due to decreased aortic pressure, decreased diastolic time, increased LVEDP & decreased perfusion of the thickened wall.

Oxygen requirements are increased disproportionately by increases in systolic pressure compared with cardiac output Thus if cardiac work is increased by increasing systolic pressure, oxygen requirements are much greater than if

the increase in work were achieved by increasing cardiac output Pressure work is more expensive than volume work This is the major factor underlying the mortality a/w Aortic stenosis

Explain in physiological terms the effect of severe aortic stenosis on myocardial supply and demand

67

Decreased Aortic pressure In AS the entire output of the LV is

ejected through a narrow valve orifice. The high flow velocity is associated with a large kinetic energy and therefore, lateral pressure is reduced

The reduction of lateral pressure in the region of the stenotic valve orifice influences coronary blood flow in patients with aortic stenosis.

The orifices of the coronary arteries are located just behind the valve leaflets and orientated at right angles to the direction of blood flow through the aortic valve.

Therefore the lateral pressure is the component of total pressure which propels blood through the coronary arteries, if this is reduced then flow into the coronary arteries is reduced.

Increased LVEDP Because of the high intraventricular

pressure during systole in AS, little blood flows through the coronary arteries during systole

Therefore, extra blood flow is required during diastole to make up the difference

The hypertrophied muscle of the LV also frequently has a relatively deficient coronary vasculature

The hypertrophied ventricle exhibits diminished compliance, as demonstrated by the higher LEVDP and increased dependence on atrial contraction for filling.

The raised EDP compresses the inner layers of the heart leading to diminished blood flow during diastole

Explain in physiological terms the effect of severe aortic stenosis on myocardial supply and demand

68

Decreased diastolic time Because of the high intraventricular

pressure during systole in AS, little blood flows through the coronary arteries during systole

Therefore, extra blood flow is required during diastole to make up the difference

The increased resistance created by the stenosis means it takes longer for the LV to complete systole leading to less time in diastole, leading to less perfusion time for the LV.

It also means the ventricle works for longer, increasing O2 consumption

Describe the factors influencing hepatic blood flow I

69

Liver blood supply is unique as it is supplied by both the hepatic artery and the hepatic portal vein

Both hepatic artery and portal vein contribute to hepatic oxygenation Total Hepatic blood flow is ~ 1500ml/min (25-30% CO)

Hepatic artery 1/3 of total hepatic blood supply(500ml) ; mean pressure 90 mmHg: hepatic venous pressure is 5mm Hg 40-50% of O2 supply O2 Saturation 97%

Portal Vein: 2/3 total hepatic blood supply (1L) ; mean pressure 10 mmHg; 50-60% of O2 supply since the portal vein drains the blood from the stomach, spleen, pancreas, and intestine, it is

rich in nutrients but already partially deoxygenated O2 saturation ~85% (fasting) 70% (during digestion)

Liver has high baseline blood flow any increase in O2 demand is met by increased O2 extraction rather than an increase in blood flow

However, the hepatic artery blood flow does change in response to changes in the portal vein flow A reduction in the portal vein flow is a/w and increase in hepatic arterial flow by 22-100%

Hepatic blood flow is controlled by both intrinsic and extrinsic mechanisms

Hepatic arterial Flow = Mean Arterial Pressure - hepatic venous pressureHepatic vascular resistance

Portal venous Flow = Portal Venous pressure - hepatic venous pressureHepatic vascular resistance

Describe the factors influencing hepatic blood flow II

70

Intrinsic Control Some degree of autoregulation can be

demonstrated in the hepatic artery When hepatic arterial pressure is reduced, flow is

maintained until SBP is below 80mmHg This is when the hepatic artery tone is lowest

The portal venous system has no autoregulation and flow is linearly related to pressure

The second intrinsic mechanism is the Hepatic Arterial Buffer Response, a semi-reciprocal interrelationship between portal venous and hepatic arterial flows A fall in portal venous blood flow hepatic

arterial resistance arterial flow As portal vein blood flows are not autoregulated,

there is little change in the portal vein blood flow when the hepatic artery is reduced

It is suggested that the HABR is due to intrahepatic levels of adenosine. portal blood flow adenosine build up vasodilation

An increase in hepatic venous pressure hepatic arterial resistance, possible due to a myogenic mechanism hepatic arterial flow Seen in CCF

Extrinsic Control Neural and blood-borne factors can modify

hepatic arterial blood flow Hepatic artery has α , β & dopamine receptors The portal vein has only α & dopamine receptors Adrenaline causes portal venous constriction and

initial vasoconstriction followed by vasodilation Dopamine has little effect on hepatic vasculature

at physiological concentrations Glucagon also increases hepatic arterial flow by

vasodilation Vasoactive Intestinal Peptide and secretin

vasodilate the hepatic artery but have minimal effect on the portal system

Angiotensin II constricts both the hepatic and portal system

Vasopressin vasoconstricts the hepatic vasculature and thus reduces portal blood flow

Feeding increase intestinal blood flow and this dramatically increase hepatic blood flow

During normal spontaneous respiration hepatic venous outflow decrease with inspiration and increases with expiration

Describe the factors influencing hepatic blood flow III Extrinsic Control Cont.

Vigorous exercise causes splanchnic vasoconstriction, leading to reduced hepatic blood flow.

Hypocapnia can reduce hepatic blood flow by 30% mainly due to a reduction in portal venous blood flow caused by an increased resistance in the portal system

Hypercapnia greatly increases hepatic blood flow due to an increase in portal venous blood flow

Hyperoxia has little effect on both arterial and portal blood flows

Hypoxia initially decrease hepatic arterial flow, which returns to normal within 20 mins and has minimal effect on the portal system

In acute haemorrhage, there is greater reduction in portal venous blood than arterial flow The oxygen supply to the liver is maintained

increased extraction also, SNS stimulation a/w hypervolemia can

mobilise about 50% of the reservoir blood in the liver into the systemic circulation

Spinal and epidural anaesthesia reduce total hepatic blood flow Due to reduced portal blood flow and reduced

MAP IAA generally reduce total hepatic blood

flow. The greatest reduction is with halothane Iso, Sevo and Des generally maintain hepatic

oxygenation IV anaesthetic agents, Propofol and

Thiopentone have been shown to cause a dose dependent reduction in hepatic blood flow Presumable due to a reduction in CO and

obtundation of the HABR

71

Briefly Outline the differences between the Pulmonary Circulation and the Systemic Circulation I Pressures

The pulmonary circulation is a low resistance, low pressure system in series with the right ventricle Pressures 25/8 (15) mm Hg Pulmonary Capillary Pressure 8mm Hg LA Pressure 5mm Pressure Gradient of 15-5 =5 mm Hg

The Systemic circulation is a high resistance, high pressure system in series with the Left ventricle Pressures 120/80 (100) mm Hg Systemic capillary Pressure 20mm Hg RA Pressure 2 mm Hg Pressure Gradient of 100-2 = 98 mm Hg

A consequence of the pulmonary low pressure system is that hydrostatic pressure has a significant effect on the lung Perfusion pressure decreases from base to apex

5mm Hg at apex to 25mm Hg at base May result in mismatch of perfusion with alveolar

ventilation 4 zones

The Systemic circulation is not greatly affected by gravity

72

Briefly Outline the differences between the Pulmonary Circulation and the Systemic Circulation II Blood Volume

The blood volume of the erect lungs is about 450 mL, about 9 % of the total blood volume of the entire circulatory system.

Approximately 70 mL of this pulmonary blood volume is in the pulmonary capillaries ,and the remainder is divided about equally between the pulmonary arteries and the veins

Structure The pulmonary vascular bed resembles the systemic one, except that the

walls of the pulmonary artery and its large branches are about 30% as thick as the wall of the aorta, and the small arterial vessels, unlike the systemic arterioles, are endothelial tubes with relatively little muscle in their walls.

Pulmonary Vascular Resistance Affected by CO

Unlike other individual organs which receive a proportion of CO the lungs receive the whole CO.

As cardiac output increases the Pulmonary blood flow must increase to match the cardiac output and can increase several fold with little change in PA pressure PVR must fall. Done by 2 mechanism; Passive distension and recruitment of closed pulmonary

capillaries, particularly in the upper zones of the lung, allow PVR to fall as Blood flow There is no myogenic or metabolic autoregulation is present in the PC

Affected by lung Volume PVR increases at both low and high lung volumes, it is at its lowest at volumes close

to FRC At low lung volumes PVR is high because extra-alveolar vessels become narrow as

they contain smooth muscle and elastic tissue, which resist distension and tend to reduce their calibre

At high lung volumes PVR is high because the capillaries are stretched and their calibre is reduced

73

PVR = (Mean PAP – PCWP) x 80 =100 dyneseccm-5 Cardiac output

Briefly Outline the differences between the Pulmonary Circulation and the Systemic Circulation III

74

Response to Hypoxia: Hypoxic Pulmonary Vasoconstriction When the concentration of oxygen in the air of the alveoli decreases

below normal—especially when it falls below 70 per cent of normal (below 73 mmHg PO2)—the adjacent blood vessels constrict, with the vascular resistance increasing more than fivefold at extremely low oxygen levels.

This is opposite to the effect observed in systemic vessels, which dilate rather than constrict in response to low oxygen.

Autonomic Innervation The pulmonary system is innervated by both the SNS and PNS but the density

of receptors is much less Role unclear as pulmonary vessels normally maximally dilated and local factors,

especially PO2 is more important Filtering

The pulmonary capillary bed filters the whole or the venous return and is the only capillary bed in the body that can do this.

What is 2, 3 DPG? How is it produced in the RBC and how does it interact with haemoglobin? What is its relevance in altitude exposure, anaemia and stored blood? 2,3 Diphosphoglycerate is produced by a side shunt

(Rapoport-Leubering shunt) from glycolysis, (Embden–Meyerhof pathway), and is present in large quantities in the RBC At high pH The DPG mutase activity is enhanced and the DPG

phosphatase activity is inhibited levels Because acidosis inhibits red cell glycolysis, the 2,3-DPG

concentration falls when the pH is low. It binds to the β chains of Hb, changing the proteins

configuration and reducing oxygen affinity for Hb, resulting in a right shift of the Oxygen-Haemoglobin dissociation curve

This right shift does not impair oxygen uptake in the lungs, but significantly improves oxygen unloading in the tissues

It is important to note that 2,3 DPG has no effect on foetal Hb as it contains γ chains instead of β chains and this explains why the p50 of the foetal Hb is shifted to the left

Conversely, thyroid hormones, growth hormones, and androgens can all increase the concentration of 2,3-DPG and the P50.

75

What is 2, 3 DPG? How is it produced in the RBC and how does it interact with haemoglobin? What is its relevance in altitude exposure, anaemia and stored blood? II

76

Red cell 2,3-DPG concentration is increased in anaemia and in a variety of diseases in which there is chronic hypoxia. This facilitates the delivery of O2 to the tissues by raising the PO2 at which O2 is released in peripheral capillaries.

Anaemia Hypoxia due to anaemia is not severe at rest unless the haemoglobin deficiency is marked, because red blood cell

2,3-DPG increases The P50 is approximately 3.8mmHg higher than control levels

Altitude The ODC is shifted to the right within 12 hours of altitude exposure due to the effects of an increase in the amount of

2,3-DPG Disputed by Nunn: PaO2 at 4000M is 52.5 mmHg- below which a right shift of the ODC is less advantageous since oxygenation in

the lung is impaired to a degree which is barely outweighed by improved off-loading in the tissues The respiratory alkalosis produced by the increase in MV, induces the production of 2,3-DPG

Hyperventilation commences at altitudes above 3000M and increases progressively with altitude to reach a maximum at 6000m where minute ventilation is approximately 160% of that at sea level

Stored blood In blood that is stored, the 2,3-DPG level falls and the ability of this blood to release O2 to the tissues is reduced. Due to decreased metabolic activity and acidosis This decrease, which obviously limits the benefit of the blood if it is transfused into a hypoxic patient, is less if the

blood is stored in citrate–phosphate–dextrose solution rather than the usual acid–citrate–dextrose solution. 2,3 DPG decrease to 50% by 14 days and 5% by 28 days in CPD-A

After transfusion the metabolic activity of the cells increases and levels of 2,3,DPG return to normal within 24 hours of infusion

List the physiological factors that affect left atrial pressure and explain their effects (July04: 19%) I The left atrial pressure in a healthy person

almost never rises above +6 mm Hg, even during the most strenuous exercise.

A wave :- Atrial contraction C wave : - caused by bulging of mitral valve

into the left atrium during Isovolumetric Contraction of LV

V wave:- Venous Return- a small rise in pressure when there is venous return of blood while the AV valves are closed.

X descent:– The drop in LA pressure after the aortic valve opens; it occurs because of shortening of ventricles during the rapid ejection phase pulls the fibrous AV rings downwards lengthening of the atria capacity pressure- may even become negative

Y descent: drop in pressure due to opening of MV emptying of atrium

77

List the physiological factors that affect left atrial pressure and explain their effects II Beyond a critical stage in aortic valve lesions,

the left ventricle finally cannot keep up with the work demand.

As a consequence, the left ventricle dilates and cardiac output begins to fall; blood simultaneously dams up in the left atrium and in the lungs behind the failing left ventricle.

The left atrial pressure rises progressively, and at times the mean left atrial pressure can rise to 25 to 40 mm Hg.

In mitral valvular disease, principally because of diminished excretion of water and salt by the kidneys.

This increased blood volume increases venous return to the heart, thereby helping to overcome the effect of the cardiac debility.

Therefore, after compensation, cardiac output may fall only minimally until the late stages of mitral valvular disease, even though the left atrial pressure is rising. As the left atrial pressure rises, blood begins to dam up in the lungs,

Physiological factors can be divided into 3 groups

Venous return Blood volume Posture Venous tone Intrathoracic pressure (thoracic pump) Intrapericardial pressure

Left ventricular emptying Contractility Afterload

Left ventricular filling Diastolic compliance Mitral valvular disease Variations in HR Pulmonary artery obstruction

78

Outline the systemic cardiovascular response to exercise I Reflexes

Exercise activates reflex mechanism that enhance CVS performance Cerebrocortical activation of the SNS due

to anticipation of physical activity CVS reflexes due to stimulation of muscle

mechanoreceptors during contraction The afferent limb is via small unmyelinated

fibres which activate sympathetic fibres to heart and peripheral blood vessels

Local reflexes stimulated by rapid accumulation of metabolites during muscle contraction

Baroreceptor reflexes Peripheral chemoreceptors do not play

a significant role in exercise as PaO2 and PaCO2 remain normal

In addition to the CVS reflexes, pulmonary reflexes increase depth and rate of breathing

Regional Blood Flow Blood flow is diverted to active

muscles from skin, splanchnic regions, kidneys and inactive muscles

Cutaneous blood flow decreases initially, then gradually increases during exercise with the rising body temperature

As exercise severity increases further and O2 consumptions increases to maximum levels, cutaneous vasoconstriction occurs and blood flow to the skin starts to decrease

Myocardial blood flow increases concomitantly according to metabolic demands

Cerebral blood flow remains unchanged during exercise

79

Outline the systemic cardiovascular response to exercise II Skeletal Muscle

Blood flow to active muscle increases progressively in keeping with the work rate of the tissues

Locally accumulated substances and conditions such as H+, K+ and adenosine, produce arteriolar dilation and blood flows increase up to 20 fold

Capillary recruitment increases dramatically

Net movement of fluid into the interstitial compartment occurs and lymph flow increases, aided by muscle contraction

Oxygen extraction can rise by as much as 60 times, outstripping increases in blood flow and increasing AV oxygen differences

The increase O2 extraction is aided by a right shift in the ODC aided by acidosis, CO2, 2,3 DPG and Temp

Cardiac Output The enhanced CO is mainly

achieved by increases in HR, which follows increased SNS and decreased PNS drive of the SA node

At mild to moderate work rates the HR increases proportionately to an appropriate level and then is maintained

As work increases further the HR plateaus at about 180-200 BPM

In trained athletes CO may increase 7X but SV may only increase 2X

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Outline the systemic cardiovascular response to exercise III Venous Return

The increase in CO during exercise is accompanied by a commensurate increase in VR

As a result CVP does not change significantly the Frank-Starling mechanism does not play a major role in increasing SV

When exercise becomes maximal, CVP tends to rise and FSM starts to contribute significantly

The mechanism augmenting VR include venomotor tone muscle pump activity Redirection of blood from cutaneous, renal and

splanchnic circulations thoracic pump actions due to increase RR and

TV Intravascular volume is usually slightly

reduced during exercise due to increased insensible losses from respiration and the skin. Also net capillary filtration into interstitial muscle space HCT

Arterial Pressure Both SBP and DBP increase during exercise,

although SBP increases relatively more This results in an increased pulse pressure

attributed to an increased stroke volume and higher ejection velocity from LV

This increased arterial pressure occurs in the face of a decreased SVR(2ry to vasodilation) and reflects the greatly increased CO (up to 7x)

The SNS is important in maintaining BP during exercises and if compromised by drugs or disease, effort induced hypotension or syncope can result

Isometric vs Isotonic exercise Isometric exercise causes sustained compression

of blood vessels in the muscles blood flow through the muscles and increases in total peripheral resistance There is also an increase in SNS activity rises in

both SBP and DBP as well as HR SV does not significantly increase

With isotonic exercise there is peripheral vasodilation and a fall in total SVR, SBP rises but DBP remains stable and a greater rise in SV is seen

81

Describe the factors which oppose left ventricular ejection I This is essentially the determinants

of afterload Analogy of Ohms Law V=IR (MAP-

RAP) = QSVR Afterload

Physiological Definition : Ventricular wall stress developed during systole As defined by the Law of Laplace

Physiological Index: Systolic ventricular wall stress

Practical concept: Impedance to Ejection of blood from the heart into the circulation

Practical Index: MAP Increases in aortic pressure can produce

higher peak systolic pressure's, until the point where the ventricle can not develop sufficient pressure to open the aortic valve

Factors which affect Afterload: SVR or more specifically Systemic Vascular

Impedance Metabolic/ myogenic autoregulation, SNS tone,

Hormonal control Blood Volume Factors increasing CO

Preload, exercise, anxiety catecholamines, inotropes, AII, Renin

Intrathoracic and Intrapericardial pressure In patients with poor left ventricular function or

congestive heart failure, the increase in intrathoracic pressure reduces the left ventricular transmural pressure, leading to a reduction in left ventricular afterload and an improvement in left ventricular function.

In these patients, cardiac output is relatively insensitive to the reduction in venous return because diastolic volume is elevated.

Ventricular wall thickness By applying Laplace's law, increased LV wall

thickness will decrease wall stress despite the necessary increase in LV pressure to overcome the aortic stenosis

Ventricular size In a failing heart, the radius of the LV increases,

thus increasing wall stress

82

Describe the factors which oppose left ventricular ejection II Systemic Vascular impedance is the

mechanical property of the vascular system opposing ejection and flow of blood into it. It has two components Resistive or steady flow component which

is SVR Mainly due to frictional opposition to flow in

vessels Due to compliance of vessel walls (altered by

vasoconstriction/ vasodilatation and inertia of ejected blood (altered by viscosity)

Reactive or dynamic flow component Dependent on pulsatile nature of flow and

rapidity of ejection Altered by AS and calcification of aorta Obstructive cardiomyopathy Systolic anterior motion of the mitral valve

Mainly determined by arterial elastance Ea Ea is a measure of the elastic forces in the

arterial system that tend to oppose ejection of blood into it

Note the failing heart is more sensitive to changes in Afterload

Law of Laplace The law of Laplace states

that wall stress (σ) is the product of pressure (P) and radius (r) divided by wall thickness (h): σ = Pr/2h

SVR= 80 x (MAP - CVP)/CO Normal 900-1500

dyne∙s∙cm-1 PVR= 80 x (PAP-LAP)/CO Normal 90-150 dyne∙s∙cm-1

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Describe the determinants of venous return and the effect general anaesthesia would have on these I

84

The venous return to the heart is the sum of all the local blood flows through all the individual tissue segments of the peripheral circulation

Derivation of Ohms Law V=IR I =V/R When looking at the Venous side of the circulation the resultant formula is

Venous return = (MSFP – RAP)/Resistance to Venous Return VR = (7-0) / 1.4 = 5L = CO

Therefore determinants of Venous return are The pressure gradient for venous return Resistance to Venous Return Venous Valves The Skeletal Muscle pump The Respiratory Pump The effect of ventricular contraction and relaxation Venomotor tone Posture

Describe the determinants of venous return and the effect general anaesthesia would have on these II The pressure gradient through the veins to the

right atrium is the main factor determining the rate of venous return and is equal to the difference between MSFP and the MRAP

Venous Return pressure gradient = MSFP-MRAP Mean Systemic Filling Pressure

The average of all pressures in different vessels weighted according to their relative compliances

A single hydrostatic assessment of the filling of the CVS

Indicates the pressure moving the blood back to the right atrium to maintain the CO

The static pressure in the CVS after rapid equilibration of the arterial and venous pressure that would occur if arrest was to occur

In the functioning CVS the MSFP normal value is 7 mm Hg with a range of 0-20 mm Hg

MSFP increases with venomotor tone or blood volume and falls with venodilation or blood loss

Changes in SVR do not affect MSFP

85

Describe the determinants of venous return and the effect general anaesthesia would have on these III

86

Resistance to Venous Return In the same way that mean systemic filling pressure represents a pressure pushing venous

blood from the periphery toward the heart, there is also resistance to this venous flow of blood.

It is called the resistance to venous return. Most of the resistance to venous return occurs in the veins, although some occurs in the arterioles and small arteries as well.

Why is venous resistance so important in determining the resistance to venous return? The answer is that when the resistance in the veins increases, blood begins to be dammed up, mainly in the veins themselves.

But the venous pressure rises very little because the veins are highly distensible. Therefore, this rise in venous pressure is not very effective in overcoming the resistance, and blood flow into the right atrium decreases drastically.

Conversely, when arteriolar and small artery resistances increase, blood accumulates in the arteries, which have a capacitance only 1/30 as great as that of the veins.

Therefore, even slight accumulation of blood in the arteries raises the pressure greatly—30 times as much as in the veins—and this high pressure does overcome much of the increased resistance.

Mathematically, it turns out that about two thirds of the so-called “resistance to venous return” is determined by venous resistance, and about one third by the arteriolar and small artery resistance.

Venous Return: Venous Resistance Figure 20–12 demonstrates the effect of different

levels of resistance to venous return on the venous return curve, showing that a decrease in this resistance to one-half normal allows twice as much flow of blood and, therefore, rotates the curve upward to twice as great a slope.

Conversely, an increase in resistance to twice normal rotates the curve downward to one-half as great a slope. Note also that when the right atrial pressure rises to

equal the mean systemic filling pressure, venous return becomes zero at all levels of resistance to venous return because when there is no pressure gradient to cause flow of blood, it makes no difference what the resistance is in the circulation; the flow is still zero.

Therefore, the highest level to which the right atrial pressure can rise, regardless of how much the heart might fail, is equal to the mean systemic filling pressure.

87

Describe the determinants of venous return and the effect general anaesthesia would have on these II Skeletal Muscle Pump

Alternating contractions and relaxation of limb skeletal muscle squeezes blood our of the veins towards the heart.

During standing, rhythmical skeletal muscle contractions in the veins of the leg reduce venous pressure and volume

During exercise, the skeletal muscle pump increases VR

Venous valves The limb veins have one way valves that

prevent retrograde flow and aid function of skeletal muscle pump

Ventricular Contraction and Relaxation During the rapid ejection phase of ventricular

systole, the atrial pressure falls sharply, to zero or negative values as ventricular contraction pulls the AV fibrous ring downwards lengthening and increasing the atrial volume

This increases the flow of blood into the atria from the vena cava and pulmonary veins

Respiratory Pump The respiratory cycle changes in intrathoracic

pressure facilitates VR during inspiration During inspiration the intrapleural pressure

falls from -5 cm H2O to -8 cm H2O and the descent of the diaphragm increases intra-abdominal pressure

Both increase the movement of blood from extrathoracic veins to the RA

During expiration, the effect is reversed During inspiration the thoracic blood volume

increases by 250 mL and the RV SV increases by 20 mL

The effect on the LV is different as during inspiration, the increased capacity of the pulmonary vessels decreases LVSV

The respiratory variation in LV SV is only in the order of 5%

The effect of the respiratory pump increases during exercise, but the effect is limited by the development of negative pressure and the collapse of veins as they enter the chest

88

Describe the determinants of venous return and the effect general anaesthesia would have on these III Venomotor Tone

An increase in venomotor tone in the systemic circulation, it increases the MSFP because of contraction of the peripheral vessels—especially the the veins—and it increases the resistance to venous return.

Venomotor tone has more effect on the VR when venous pressure is normal and the veins in their circular configuration contain large volumes of blood

Posture is important because it

has an effect on the pooling of blood in the venous capacitance system

Suddenly changing from supine to erect and standing still causes venous polling of blood and a decreased VR

89

90

Control of CO by VR: The role of the Frank-Starling Mechanism When one states that cardiac output is controlled

by venous return, this means that it is not the heart itself that is the primary controller of cardiac output

Instead, it is the various factors of the peripheral circulation that affect flow of blood into the heart from the veins, called venous return, that are the primary controllers

The main reason peripheral factors are usually more important than the heart itself in controlling cardiac output is that the heart has a built-in mechanism that normally allows it to pump automatically whatever amount of blood that flows into the right atrium from the veins.

This mechanism, called the Frank-Starling law of the heart, Basically, this law states that when increased

quantities of blood flow into the heart, the increased blood stretches the walls of the heart chambers.

As a result of the stretch, the cardiac muscle contracts with increased force, and this empties the extra blood that has entered from the systemic circulation.

Therefore, the blood that flows into the heart is automatically pumped without delay into the aorta and flows again through the circulation

Another important factor, is that stretching the heart causes the heart to pump faster—at an increased heart rate, as much as 75 % a small part is due to stretch of the sinus node in

the wall of the right atrium which has a direct effect on the rhythmicity of the node itself to increase heart rate as much as 10 to 15 per cent.

The stretch receptors of the atria that elicit the Bainbridge reflex transmit their afferent signals through the vagus nerves to the medulla of the brain. Then efferent signals are transmitted back through vagal and sympathetic nerves to increase heart rate and strength of heart contraction. Thus, this reflex helps prevent damming of blood in the veins, atria, and pulmonary circulation.

Under most normal unstressful conditions, the cardiac output is controlled almost entirely by peripheral factors that determine venous return.

However, if the returning blood does become more than the heart can pump, then the heart becomes the limiting factor that determines cardiac output

Control of CO by VR: Cardiac Function Curves There are definite limits to the amount of blood that the

heart can pump, which can be expressed quantitatively in the form of cardiac output curves

Figure 20–4 demonstrates the normal cardiac output curve, showing the cardiac output per minute at each level of right atrial pressure. This is one type of cardiac function curve, The plateau level of this normal cardiac output curve is about

13 L/min, 2.5 times the normal cardiac output of about 5 L/min. This means that the normal human heart, functioning without

any special stimulation, can pump an amount of venous return up to about 2.5 times the normal venous return before the heart becomes a limiting factor in the control of cardiac output.

Shown in Figure 20–4 are several other cardiac output curves for hearts that are not pumping normally. The uppermost curves are for hypereffective hearts that are

pumping better than normal. The lowermost curves are for hypoeffective hearts that are

pumping at levels below normal

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Cardiac Function Curves: Hypereffective Heart Only two types of factors usually can make the heart a better

pump than normal. nervous stimulation and

a combination of (1) sympathetic stimulation and (2) parasympathetic inhibition does two things to increase the pumping effectiveness of the heart: (1) it greatly increases the heart rate, sometimes, in young people, from the normal level of 72 beats/min up to 180 to 200 beats/min—and (2) it increases the strength of heart contraction (which is called increased “contractility”) to twice its normal strength.

Combining these two effects, maximal nervous excitation of the heart can raise the plateau level of the cardiac output curve to almost twice the plateau of the normal curve, as shown by the 25-liter level of the uppermost curve in Figure 9-11.

hypertrophy of the heart muscle. A long-term increased workload, but not so much excess load that it damages

the heart, causes the heart muscle to increase in mass and contractile strength in the same way that heavy exercise causes skeletal muscles to hypertrophy.

For instance, it is common for the hearts of marathon runners to be increased in mass by 50 to 75 per cent.

This increases the plateau level of the cardiac output curve, sometimes 60 to 100 per cent, and therefore allows the heart to pump much greater than usual amounts of cardiac output.

When one combines nervous excitation of the heart and hypertrophy, as occurs in marathon runners, the total effect can allow the heart to pump as much 30 to 40 L/min, about 2½ times normal; this increased level of pumping is one of the most important factors in determining the runner’s running time

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Cardiac Function Curves: Hypoeffective Heart

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Any factor that decreases the heart’s ability to pump blood causes hypoeffectivity. Some of the factors that can do this are the following: Coronary artery blockage, causing a “heart attack” Inhibition of nervous excitation of the heart Pathological factors that cause abnormal heart rhythm or rate of

heartbeat Valvular heart disease Increased arterial pressure against which the heart must pump,

such as in hypertension Congenital heart disease Myocarditis Cardiac hypoxia

Briefly explain the cardiovascular response to central neural blockade (July07: 42%)

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The cardiovascular effects of neuraxial blocks are similar in some ways to the combined use of intravenous α1- and β-adrenergic blockers: hypotension and bradycardia

Hypotension Hypotension after central neural blockade can be attributed to reduction in SVR and /or fall in

CO Bilateral sympathectomy causes venous and arterial vasodilation, but because of the large

amount of blood in the venous system (approximately 75% of the total volume of blood), the venodilation effect predominates as a result of the limited amount of smooth muscle in venules;

The physiological response to hypotension is compensatory vasoconstriction of veins above the level of the sympathectomy

Thus the degree of hypotension is dependent on the height of the block, the extent of venous pooling, particularly within the splanchnic capacitance vessels and the degree of upper extremity vasoconstriction this may not be sufficient to prevent significant falls in MAP if the block is extensive in contrast, the vascular smooth muscle on the arterial side of the circulation retains a considerable

degree of autonomous tone. In Young healthy subjects with good myocardial function, SVR will decrease only moderately

~15%, even with significant sympathetic blockade

Briefly explain the cardiovascular response to central neural blockade (July07: 42%)

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The cardiovascular response to spinal anaesthesia changes with age and height of the block In young, healthy patients, reductions in MAP are mild because of

compensatory upper extremity vasoconstriction However when spinal anaesthesia is extended to cervical levels, upper

extremity and splanchnic vasoconstriction is abolished and hypotension ensues

In the elderly there is a more profound drop in BP owing to an exaggerated decrease in SVR with sympathetic blockade compared to younger patients ~25% vs 15% and LVEDV decreases by 20%

Sympathetic supply to the kidneys is from T11-L1 via the lowest splanchnic nerves.

Resting sympathetic tone in kidneys is low and abolition of that tone scarcely affects RBF

Autoregulation due to myogenic mechanism and tubuloglomerular feedback maintains RBF until MAP falls below about 50mmHG

Briefly explain the cardiovascular response to central neural blockade (July07: 42%) Bradicardia

If however, the CO falls due to a reduced Preload, then hypotension may develop rapidly, especially if the block reaches the cardio accelerator fibres above at level of T1-T4 High sympathetic block to the level of cardiac

sympathetic innervation (T1-T4) reduces VR and exposes unopposed vagal parasympathetic tone leading to marked bradycardia and asystole

The cardiac response to poor VR is mediated via 3 cardiac reflexes Bainbridge reflex

Decrease in VR results in decreased efferent outflow to the cardioaccelerator fibres and a reduction in HR

SA node stretch reflex Stretch receptors in SA node respond proportionately to

VR Bezold-Jarisch reflex

Severe hypotension and bradycardia (i.e., the Bezold-Jarisch reflex) have been reported in awake, sitting patients undergoing shoulder surgery under an interscalene block.

The cause is presumed to be stimulation of intracardiac mechanoreceptors by decreased venous return, which produces an abrupt withdrawal of sympathetic tone and enhanced parasympathetic output

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The sympathectomy that accompanies the techniques depends on the height of the block, with the sympathectomy typically described as extending for two to six dermatomes above the sensory level with spinal anaesthesia and at the same level with epidural anaesthesia.

What is the Frank-Starling mechanism and describe its relationship to excitation contraction coupling I(March09: 21%) The Frank-Starling law of the

heart, states that when increased quantities of blood flow into the heart, the increased blood stretches the walls of the heart chambers.

As a result of the stretch, the cardiac muscle contracts with increased force, and this empties the extra blood that has entered from the systemic circulation.

Therefore, the blood that flowsinto the heart is automatically pumped without delay into the aorta and flows again through the circulation

When an extra amount of blood flows into the ventricles,the cardiac muscle itself is stretched to greater length.

as the muscle is stretched, the developed tension increases to a maximum and then declines as stretch becomes more extreme

Starling pointed this out when he stated that the "energy of contraction is proportional to the initial length of the cardiac muscle fibre" (Starling's law of the heart or the Frank–Starling law)

For the heart, the length of the muscle fibres (i.e., the extent of the preload) is proportional to the end-diastolic volume.

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What is the Frank-Starling mechanism and describe its relationship to excitation contraction coupling II(March09: 21%) The increased diastolic fibre length somehow facilitates ventricular

contraction and enables the ventricle to pump a greater stroke volume so that cardiac output exactly matches the augmented venous return

The developed force is maximal when the muscle begins its contractions at a resting sarcomere length of 2.0-2.4mm

At such lengths there is optimal overlap of the thich and thin filaments and a maximal number of crossbridge attachments

Stretch of the myocardium and increases in load, enhance the sensitivity of the myofilament to Ca2+ and the force of contraction, presumable by increasing the affinity of troponin C for Ca2+

An optimal fibre length apparently exists beyond which contraction is actually impaired. Therefore, excessive filling pressures may depress rather than enhance the

pumping capacity by overstretching the myocardial fibres The relation between ventricular stroke volume and end-diastolic

volume is called the Frank–Starling curve. Regulation of cardiac output as a result of changes in cardiac muscle

fiber length is sometimes called heterometric regulation, whereas regulation due to changes in contractility independent of length is sometimes called homometric regulation.

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Classify the causes of relative hypotension in the early post-operative period, giving relevant examples I (July09: 37%) Postoperative systemic

hypotension may be characterized as (1) hypovolemic

(decreased preload), (2) distributive

(decreased afterload) or (3) cardiogenic

(intrinsic pump failure) The prime determinants of

Systemic Blood Pressure are SBP= CO x SVR

Ohms Law Cardiac Output=HR X SV and Systemic Vascular Resistance

Intravascular volume depletion Persistent fluid losses Ongoing third spacing of fluid Bowel preparation Gastrointestinal losses Surgical bleeding

Increased capillary permeability

 Sepsis Burns

Decreased cardiac output Myocardial ischemia/infarction Cardiomyopathy Valvular disease Pericardial disease Cardiac tamponade Cardiac dysrhythmias Pulmonary embolus Tension pneumothorax Drug induced (β-blockers, calcium channel blockers)

Decreased vascular tone Sepsis Allergic reactions (anaphylactic, anaphylactoid) Spinal shock (cord injury, iatrogenic high spinal) Adrenal insufficiency99

Classify the causes of relative hypotension in the early post-operative period, giving relevant examples II

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Stroke Volume A main determinant of SV is Venous return. This will decrease

if there is actual hypervolemia, following blood/fluid loss, or when there is effective hypervolemia, with insufficient volume to effectively fill the capacity of the venous system Effective hypovolaemia may be associated with neuroaxial

(Sympathetic block), with peripheral vasodilation due to pyrexia, sepsis or allergic reactions A patient undergoing surgery in the lithotomy position under subarachnoid

block may be able to maintain adequate venous return to the heart, until the legs are laid out flat and the blood pools in the expanded venous compartment

Stroke volume can also be diminished by myocardial depression, injury or ischaemia

Classify the causes of relative hypotension in the early post-operative period, giving relevant examples III

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Heart Rate Bradycardia

in the PACU is often iatrogenic. Drug-related causes include β-blocker therapy, anticholinesterase reversal of neuromuscular blockade, opioid administration, and treatment with 2 agonists

Procedure- and patient-related causes include bowel distention, increased intracranial or intraocular pressure, and spinal anesthesia. A high spinal block that blocks the cardioaccelerator fibers originating from T1 through T4 can produce severe bradycardia. The resulting

sympathectomy, bradycardia, and possible intravascular fluid volume depletion and associated decreased venous return can produce sudden bradycardia and cardiac arrest, even in young healthy patients

Tachycardia Tachyarrythmias can compromise diastolic filling and coronary artery perfusion Common causes of sinus tachycardia in the PACU include pain, agitation, hypoventilation with associated hypercapnia, hypovolemia, and

shivering. Less common but serious causes include bleeding, cardiogenic or septic shock, pulmonary embolism, thyroid storm, and malignant

hyperthermia. Dysrhythmias

Can result in reduced cardiac output due to poor ejection/filling of blood Perioperative cardiac dysrhythmias are frequently transient and multifactorial. Reversible causes of cardiac dysrhythmias in the perioperative period include hypoxemia, hypoventilation and associated hypercapnia,

endogenous or exogenous catecholamines, electrolyte abnormalities, acidemia, fluid overload, anemia, and substance withdrawal SVR

A decrease in SVR is associated with most anaesthetic agents and their effects may persist into the recovery period Other important influences on SVR include pyrexia, hypercapnia, sepsis and allergic reactions

It is important to remember that pressure is not the same as flow and that as long as the patients brain is receiving oxygenated blood (as manifested by normal cerebration) the absolute pressure is of little importance

Outline the factors that determine coronary vascular resistance

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