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191 Cards in this Set

  • Front
  • Back
What will happen to the arterial pressure and venous pressure if there is a fall in TPR, but CO remains constant?
Arterial pressure = CO x TPR
What happens to venous pressure and arterial pressure when TPR rises but CO remains constant?
What happens to venous pressure and arterial pressure when TPR rises but CO remains constant?
What happens to arterial and venous pressure when CO rises but TPR stays the same?
What happens to arterial and venous pressure when CO falls but TPR stays the same
What happens if there is an increase in the demand for blood?
- An increase in need raises the output of metabolites from cells = metabolic demand
- This leads to vasodilation and a fall in TPR
- If cardiac output remains the same, this will cause a fall in arterial pressure and a rise in venous pressure
- The heart needs to pump more blood to meet the demand which has been expressed in terms of changes in TPR, arterial pressure and venous pressure
- The heart responds to these changes to meet the demand, the change in venous pressure being particularly important
- The response is partly automatic and intrinsic to the heart itself and involves in changes in stroke volume
- The response is aided by reflex action (involving especially the baroreceptor reflex) involving changes in contractility and rate
Define the terms pre-load and after-load on the ventricular myocardium
- Pre-load = load on the ventricular myocardium during diastole
- After-load = load of the ventricle when is has to eject blood into the circulation during systole
What are the factors that determine how much the ventricles fill during diastole?
- As the ventricle fills its pressure rises somewhat
- Filling will cease onece the pressure equals venous (filling) pressure
- The higher the venous pressure the more the ventricles will fill
- The relationship between the end-diastolic volume in the left ventricle and venous pressure is almost linear
- However, the relationship is determined by ventricular compliance
- Ventricular compliance may be reduced in disease e.g. both in ventricular hypertrophy and in restrictive cardiomyopathy
- In these conditions the compliance of the ventricle is reduced and it requires a higher venous pressure to fill the heart = higher slope
Describe how changes in end-diastolic volume affect the force of contraction of the myocardium during the following systole
- Starlings law of the heart = the amount of stretch the heart undergoes determines the strength the heart will contract
- Therefore, and increased end-diastolic volume will increase the force of contraction of the myocardium during sytole
- Increase of filling pressure → increase in end diastolic volume → increase in stroke volume
Describe the relationship between venous pressure and stoke volume at a constant afterload
- The Starling curve relates stroke volume to the filling pressure
- In diastole, the ventricle is connected to veins, so venous pressure determines the end-diastolic stretch, or pre-load' on the myocardium
- Once systole beins, the ventricles are isolated from the veins but connected to the arteries, and the force necessary to expel blood into the arteries, or the 'after-load', determines what happens during systole
- Pre-load and after-load may vary independently
- An increase in venous pressure (and therefore end-diastolic volume) will lead to an increase in stroke volume (so more in = more out), at constant afterload
- The slope of this relationship gives the contractility of the ventricle
- The contractility can be altered by noradrenaline or adrenaline
Define contractility and describe how the Starling curve is changed by factors that increase or decrease the contractility of the ventricular myocardium
- Increased contractility may cause increased stroke volume at a lower end-diastolic pressure
- Heart failure = reduced contractility so requires a higher pressure to avoid arterial pressure loss
How can the heart maintain its output in the face of an increased TPR is venous return is maintained?
The heart may also maintain its output in the face of an increased TPR or if the aortic pressure is increased, if venous return is maintained:
an increase in after-load.
- If the resistance is raised, it becomes harder to eject blood → immediate effect is a reduction in stroke volume
- If stroke volume is reduced (and the ventricle empties less) → once it has filled again, end-diastolic volume will have increased
- An increase in end-diastolic volume enables the heart to do more work.
- Stroke volume then recovers, but end diastolic volume has increased (and the ejection fraction has fallen)
- If TPR increases, an increased end-diastolic volume will permit ventricular pressure to rise further in systole maintaining stroke volume.
- Stroke work will increase due to an increased afterload, provided venous return is maintained
- However, a rise in TPR might also be expected to reduce venous pressure (and increase arterial pressure)
– and this will reduce EDV and stroke work, helping correct the rise in arterial pressure that would otherwise occur
- Conversely, a fall in TPR is also likely to raise venous pressure – and this will increase EDV and stroke work, helping correct the fall in arterial pressure that would otherwise occur
Consider the consequences of a fall in arterial blood pressure
- Increase in venous pressure and therefore stroke volume
- In addition, through reflex action
• Increase the heart rate reducing the vagal (sympathetic) tone to the heart
and increasing sympathetic activity
• Increase the contractility of the heart increasing sympathetic activity → pump more blood
• Effects of blood vessels as well – vasoconstriction will raise TPR and this rise will help restore blood pressure.
How do arterial receptors detect changes in arterial changes
- These afferent nerve fibres respond to changes of blood pressure through stretch of the walls of the carotid sinus and aortic arch.
- Impulses are conducted at lower frequency at low pressures and at raised frequency at high pressures.
Describe the effects of a fall in arterial pressure, detected by the arterial baroreceptors, upon heart rate and ventricular contractility
- Overrides any intrinsic effects of the heart
- Baroreceptors are blunted in people with hypertension = sensitized to a high range of pressures
Decribe the effects of rises of venous pressure on heart rate
- Both atria contain stretch receptors that sense filling pressure – at the atrio-venous junctions
- Their principal function is to control extracellular fluid and blood volume (regulates Na+ excretion from the body)
(see Urinary module)
- But they also have an effect on heart rate at high end diastolic volume = puts out hormones allowing pressure etc to change
What occurs at high end-diastolic volumes?
At high end-diastolic volumes two things happen:
1. The diastolic pressure becomes high – venous pressure will be high – increasing the chance of oedema
2. The heart responds less well with an increase in stroke work to a further increase in end-diastolic volume
What are the effects on venous and arterial pressures if the heart stops?
- Arterial pressure will fall
- Venous pressure will rise
- They will come to be equal if the heart stops and will be determined
by:
• the blood volume
• the compliance of
the circulation
= the mean filling pressure of the circulation
Describe the intrinsic reflex mechanism of the heart
- An increase in venous pressure – an increase in filling pressure – will increase the stroke volume
- Intrinsic mechanism – through Starling’s Law of the Heart
- A decrease in arterial pressure will reduce the work the heart has to do to pump out the same volume of blood.
- If venous return remains the same, the same stroke volume will be ejected at a lower end diastolic volume.
- However this response to a change in arterial pressure principally depends on a reflex mechanism, responding to altered information from baroreceptors in the carotid sinus and aortic arch, altering cardiac contractility
Describe the reflexes mechanisms associated with arterial pressure
- A fall in blood pressure risks supply to the brain (and may cause syncope)
- The resistance to flow must therefore rise elsewhere in the circulation (eg skin, gut)
- Principally through a reflex response to information from the baroreceptors in the carotid sinus and aortic arch
- So falls in arterial pressure lead to vasoconstriction
- A fall in arterial pressure will also lead to venoconstriction, increasing the return of blood to the heart
What drives the cardiac output - the heart or the circulation?
- Cardiac output = heart rate × stroke volume
- If the heart rate is raised
→ initially the cardiac output will increase
but the venous pressure with fall as a result
→ reduced end-diastolic volume
→ reduced stroke volume, correcting CO
- The heart does not drive the circulation, but is driven by it
= the output of the heart meets the demands of the circulation
Describe the effects of ingestion of food on the circulation
- Expect, and can show, that blood flow increases
→ Increasing GI motility, secreting endocrine and exocrine factors, absorbing products of digestion
→ Postprandial hyperaemia
- Number of factors cause increased flow:
• Metabolic factors (adenosine, CO2, hypoxia)
• Effects of absorbed substances
• Vasoactive GI hormones
• Neural effects
- GI tract circulation important element in TPR – these changes will reduce TPR
- This must be corrected across the system
- Rise in venous (filling) pressure increases stroke volume (Starling’s Law)
- Fall in arterial pressure
means that contractility of the heart is increased by reflex means.
- Also then gives an
increase in CO
- Tending to correct both arterial and venous pressure
Describe the cardiovascular response to exercise
- Requires a large increase in blood flow to skeletal muscle
• Vasodilatation in skeletal muscle reduces TPR
• Movements of skeletal muscle will increase venous return and raise venous pressure
- Might envisage exercise as a situation where the required increase in CO can be met through an increase in stroke volume
- But if end-diastolic volume becomes very large:
• End diastolic and therefore venous pressure becomes high, increasing likelihood of pulmonary oedema
• The stroke volume ceases to increase with end-diastolic volume
- So another mechanism dominates
• Cardiac output rises – usually up to 3× ( but can rise 5×)
• Principally through an increase in heart rate (from 60 to 180 beats per min)
• Relatively little increase (10 – 20%) in stroke volume
Describe the cardiovascular response to stading from a lying position
- Gravity has effects on the circulation – and particularly on venous return
- Lying down – lower extremities are at the same level as the heart
- On standing - adding the column of blood below the heart to the pressure
- Need muscle pump etc to return blood to the heart – a particular problem for superficial veins
- Blood will be pooled in the superficial veins of the legs
- Central venous pressure falls
- End-diastolic volume will fall and cardiac output will go down
- If the TPR is unchanged, arterial pressure will FALL too
- Difficult situation for the heart to respond to through Starling's Law
- This must be corrected through reflex action (see diagram)
- If this compensation is insufficient (or not fast enough) may lead to fainting
= postural hypotension
- If other physiological responses are reducing TPR the response to a change of posture may be compromised (i.e. enhances chances of failure)
• after eating a meal → vasodilatation in GI tract
• in hot environment → vasodilatation in skin
• If there is pharmacological blockage of a1 receptors for example → can't constrict blood vessels in response so are difficult for patients to take as can't respond to changes in blood pressure
What occurs in the cardiovascular system due to hemorrhage?
- Dangerously rapid loss of blood
- Fall in central venous pressure
- Causes a reduction in stroke volume and so a reduction in cardiac output
- Unless there is a change in peripheral resistance arterial pressure will FALL
- The heart cannot itself respond to correct these changes
• May become self-reinforcing owing to reduced blood flow → build up of vasodilator metabolites, which reduces TPR
• Leading to a further fall in blood pressure to haemorrhagic shock and death = can be sudden so must treat rapidly and give fluids to restore volume
- The immediate response to haemorrhage is principally through reflex responses to the change in blood pressure
- And subsequently through restoration of blood volume at the expense of interstitial fluid
- Recruiting from the venous reservoir is essential (see diagram)
Describe the effects on hydrostatic pressures during hemorrhage
- Recruiting from the venous reservoir is essential, since increasing the cardiac output would tend to lower venous pressure further.
- The heart rate can become very high – and the pulse weak
- At blood pressures below ~40mm Hg, the cerebral ischaemia that ensues stimulates an intense sympathetic discharge
- Fluid is transferred from the extracellular space – from interstitial fluid – into the vasculature
- This will reduce hydrostatic pressure, so that oncotic pressure is always higher
- This causes increased reabsorption throughout the capillary bed and blood volume is corrected within 1/2 hour
- Reabsorption of interstitial fluid restores blood volume
• though at the expense of haematocrit and of plasma proteins (colloid osmotic pressure will fall)
- Other longer term physiological mechanisms will:
• restore extracellular fluid volume – for example, angiotensin II will stimulate secretion of aldosterone, &
haematocrit through increased red cell production.
Describe a situation with long-term increases in blood volume and their effect on the cardiovascular system
- Occasionally changes in renal function or in diet – perhaps a high Na+ diet - may lead in increases in extracellular fluid volume
- Increase in blood volume will raise venous pressure
→ increased end-diastolic volume
→ increased cardiac ouput
increasing arterial pressure
- Increase in flow may lead to autoregulatory increases in TPR
- These changes lead to hypertension
- Reversible in the short term = aided by the use of diuretics favouring the excretion of salt and water
- But in the longer term changes in the walls of blood vessels make reversal more difficult and blunt the baroreceptor reflexes
- A similar situation is seen in Eisenmengers syndrome = changes in blood vessel histology makes them less compliant → blunted reflexes. This can be picked up in the eyes = silver-wiring
Describe the relationship between pressure, resistance and flow in the systemic circulation
- Flow will be 5l/min at any level of the circulation
- Pressure drop is different in different parts of the circulation = reflects differences in resistance to flow
- Greatest pressure drop is found across the arterioles, which have the largest total peripheral resistance
- Pressure drops from the aorta to the veins
- Blood flow is generated by a pressure gradient
- Flow is proportional to the pressure difference between the ends of the vessels, other things being equal (so increase the pressure and increase flow rate)
- Therefore, for a given pressure gradient, the flow is determined by the resistance of a vessel
PRESSURE GRADIENT = FLOW x RESISTANCE
- Also, for any given flow, the pressure gradient needed is determined by the resistance of the vessel
FLOW = PRESSURE GRADIENT / RESISTANCE
- The resistance of the vessel depends on its radius, so reduce the radius and increase the resistance of the vessel
Define flow and velocity
- Flow = the volume of fluid passing a given level of the circulation per unit time - measured in ml/s or l/min
- Velocity = the rate of movement of fluid along a vessel - measured in cm/s
- Although the flow of blood will be the same through the circulation, its velocity will vary
Describe the relationship between flow and velocity
- The flow must be the same at all points along a system of vessels
- The velocity will vary along the length if the cross-sectional area of the vessel changes
- At a given flow, velocity is inversely proportional to cross-sectional area → smaller volume of blood can be held at any one time in a small vessel and so must flow faster
- VELOCITY (V) = FLOW (Q) / AREA (A)
- if the flow was the same in each,
V1/V2 = A2/A1 = R2^2/R1^2
- Hence blood flows through capillaries at a lower velocity than arterioles as the total cross-sectional area of the capillaries is much larger
- Decreasing the area of the vessel decreases the flow of blood and increases the resistance at that vessel
Describe what is meant by laminar flow and its effects
- Fluid will not move with the same velocity across the width of the tube - its flow is laminar
- Laminar flow will mean that the velocity is lowest - essentially stationary - at the edges, and highest at the centre of the tube where the edge effect is weakest
- Laminar flow means that the width of the tube greatly affects its resistance, which thereby affects the velocity of blood
- Reducing the radius results in a reduction in the velocity in the middle of the tube = the mean velocity is reduced
- At a constant pressure gradient, mean velocity is proportional to r^2 due to increased resistance as a result of laminar flow
- So, when decrease the width of the tube, and you increase the resistance and decrease the velocity of blood (at constant pressure)
- SO, since flow = velocity x πr^2,
FLOW proportional to πr^4
- Thus, if you reduce width of the tube by 1/2 the flow rate reduces by 16
- To sustain this constant flow, the pressure gradient will need to be radically increased
- In this situation (P increase), reducing the radius results in an increase in the velocity in the middle of the tube: the mean velocity will now be increased
What is Poiseuille's law, and how does it effect flow?
- The resistance of the vessel depends on its radius, length and the viscosity of the fluid
- Total resistance in the vasculature is greatest in the arterioles, through a combination of their length and reduced radius without a significant change in total cross-sectional area
- Capillary resistance is less than arteriolar resistance because capillaries are shorter, large numbers of them occur in parallel, and they have a singly file rather than laminar flow
- Total resistance is dependent upon smooth muscle tension, which controls the arteriolar radius
What is Poiseuille's law, and how does it effect flow?
- The resistance of the vessel depends on its radius, length and the viscosity of the fluid
- Total resistance in the vasculature is greatest in the arterioles, through a combination of their length and reduced radius without a significant change in total cross-sectional area
- Capillary resistance is less than arteriolar resistance because capillaries are shorter, large numbers of them occur in parallel, and they have a singly file rather than laminar flow
- Total resistance is dependent upon smooth muscle tension, which controls the arteriolar radius
Describe what is meant by viscosity and the effect of viscosity on flow
- Viscosity is defined as the 'lack of slipperiness' and is a measure of the internal friction within a moving fluid
- According to Poiseuille's law, viscosity is proportional to resistnace, so it plays a role in blood flow
- A result of laminar flow is that red cells tend to get borne along the most rapidly moving stream in the centre of blood vessels, raising its viscosity
- Polycythaemia is caused by physiological adaptation to chronic hypoxia or a lyeloproliferative disease resulting in an increased red blood cell production by the bone marrow. Viscosity, and therefore resistance are increased, leading to hypertension and sluggish blood flow
Describe:
1. The changes in velocity and pressure when the flow is constant and the radius is halved
2. The changes in velocity and flow when the pressure is constant and the radius is halved
What is meant by turbulent flow?
- Under certain circumstances the flow becomes turbulent - such flow gives rise to sounds
- The layers (laminae) of laminar flow break up and flow becomes disordered
- Flow is more likely to become turbulent if:
1. Velocity is high (main)
2. Viscosity of blood is low
3. Blood vessel diameter is high
- Reynold's numbers tend to decrease when the diameter and velocity decrease
- Turbulent flow is noisy and will give rise to murmurs or bruits
- In turbulent flow, the resistance to flow is increased.
- Turbulent flow results in damage to endothelium and leads to damaged intima and arterial disease
What is the effect of branching of the circulation?
- At constant laminar flow:
- Expectation is that smaller vessels will have a higher resistance than larger ones. For individual vessels this is true
- However, for the circulation as a whole, the resistance of the capillaries is not that much greater than that of the aorta as formed in a bed → most resistance resides at the arterioles
Describe the effects of combining flow resistances in series and parallel
- Resistances combine just like electrical resistances do:
- For vessels in series, resistances add, and flow through each will be the same
- For vessels in parallel, the overall resistance is reduced and flow through each vessel will be in inverse proportion to its resistance
- Just are with electrical resistances and constant current, the voltage drops in proportion to each resistance
- So in the circulation the cardiac output flows through each part of the circulation and the pressure drops with the resistances through which blood flows
Describe the pattern of flow resistance and pressure over the systemic circulation
Describe how the distensibility of blood vessels affects the relationship between flow and pressure
- Blood vessels are not rigid = they are distensible - especially so with the veins
- They have blood inside them under pressure
- They may have external pressures acting on them = hydrostatic pressure of tissues etc.
- Transmural pressure = pressure across the wall of the vessel
= P(intravascular) - P(extravascular)
- Transmural pressure tends to stretch the vessel
- With a rigid tube resistance is constant
- With a distensible tube, an increase in pressure stretches walls lowering resistance → tendency for resistance to fall with increasing pressure
- Conversely, if pressure falls towards 0, vessel collapses and flow ceases.
- Transmural pressure must be >0 to permit vessel to be open (so intraluminal pressure must be larger than extralminal pressure)
- The distensibility of blood vessels gives them capacitance
- As vessels widen with increasing pressure, transiently more blood will flow in than out
- The vessel will store blood - the more distensible the more blood will be stored
- Veins are particularly compliant and hold ~67% of the circulating blood volume
What is systolic and diastolic arterial pressures and pulse pressure and give typical values
- In resting conditions, the left ventricle puts into the aorta around - 5 l.min-1
- This is the cardiac output
- Cardiac output = stroke volume × heart rate
- Heart is ejecting blood only during systole (for ~300ms)
- No blood is ejected during diastole (~500 - 600ms)
- Systolic blood pressure is typically 120mmHg
- Diastolic blood pressure is typically 80mmHg
- Pulse pressure = systolic – diastolic pressure = 40mmHg
- Mean blood pressure = diastolic + 1/3 × pulse pressure = 93mmHg
Why do the aorta and major arteries have distensible walls?
- If the aorta and major arteries had completely rigid walls pressure would rise to its maximum during systole and would fall to 0 in diastole
- Flow would therefore follow pressure and be intermittant
- This would be energetically be very costly to the heart
How do the aorta and major arteries maintain blood flow throughout the cardiac cycle?
- As blood is pumped into the aorta and major arteries they stretch
- Thus in systole, more blood flows into the arteries than out of them
- In diastole the walls of the aorta and elastic arteries recoil, using the potential energy stored in their walls
- This maintains blood flow, and although the flow is pulsatile, it is never intermittant
- This means that pressure rises to a maximum during systole and falls to a minimun during diastole → and flow follows pressure and is pulsatile
What are the 2 major factors that affect systolic and diastolic pressure?
1. How much blood the heart puts into the aorta and arteries = the stroke volume
2. How much blood leaves the arteries during systole =
• the peripheral resistance of the arterioles
• the compliance of the aorta and arteries = how easy it is to stretch them
- The pulse pressure in particular is determined by these factors
- Change in pressure during the cycle = change in volume in the arteries / compliance of the arteries
Describe the association of arterial compliance and age
- One of the factors that results in pressures rising with age = much less compliant as age, causing a wider blood pressure, increased pulse pressure and causing hypertension
Where does the main peripheral resistance occur?
- Arterioles determine peripheral resistance and arteries put blood into arterioles, and this is where the main resistance to flow in the circulation resides
- Arterioles also determine the flow of blood to a different organs and tissues, changing the resistance in different parts of the circulation
- Increased of blood to one organ → need to make compensation in rest of body to help maintain blood pressure e.g. increase PR in other places or increase CO
What are the factors that control vasoconstriction and vasodilation?
- TPR is varies by vasoconstriction and vasodilation as resistance to flow varies inversely with r^4
- Blood in vessels tend to be under vasomotor tone, in part owing to sympathetic action, which can cause constriction or dilation
- Vasodilator metabolites may also help control blood vessels:
• H+
• K+
• adenosine (released by cells whose O2 demand is high)
• CO2
• hypoxia (in the systemic circulation)
- These factors act paracrinely to relax vascular smooth muscle leading to vasodilation = oppose the action of sympathetic nerves
- Metabolites are washed away by blood flow = balance of 2 opposing effects
What is reactive hyperaemia?
- Measure blood flow to the arm and cut off the circulation for 1-2 mins
- During cessation of blood flow, metabolites accumulate, so arterioles will dilate maximally
- Therefore, when blood is returned supply flow is very high as the resistance to flow has decreased
- However, blood flow will wash away the vasodilator metabolites, reducing their concentration and the blood vessel will be constricted
Describe the balance between action of the sympathetic innervation and of vasodilator metabolites to match flow to metabolism
- An increaes in metabolims will increase the concentration of vasodilator metabolites
- This increase will cause vasodilation
- Vasodilation will increase flow, which will help regulate the concentration of metabolites
- More metabolism → more metabolites → more flow
- Less metabolism → less metabolites → less flow
How do vasodilator metabolites help vessels respond to a change of supply pressure
- An increase in supply pressure will increase flow
- This increase will reduce the concentration of vasodilator metabolites
- Vasoconstriction will result (autoregulation) which will help restore the flow to its appropriate level.
- More pressure → more flow → less metabolites → vasoconstriction
- Less pressure → less flow→ more metabolites → vasodilatation
How can vasodilator mechanisms compensate for arterial disease?
- Increase in resistance, resulting from coronary artery disease, is compensated by the effect of the release of vasodilator metabolites.
- At rest, this will overcome considerable occlusion of the vessel.
- However, when the heart demands an increased oxygen supply, these physiological mechanisms fail to compensate completely with smaller lesions.
- This means that only a 70-80% obstruction will show signs of disease at rest
Give 3 factors, other than vasodilator metabolites, that may help to control the blood flow in the microcirculation
1. Myogenic contraction of vascular muscle important in autoregulation, especially in the kidney where there is a need to maintain flow over a wide range of perfusion pressures
2. Circulating factors e.g. angiotensin II
3. Factors released from endothelial cells = act locally in smooth muscle e.g. NO
Describe how myogenic contraction occurs
- An increase of pressure → an increase in flow and stretch of vessel wall
- This stretch of smooth muscle cell stimulates their contraction → vasoconstriction and resuction / restoration of flow
- This contraction is myogenic = the stretch is sense by the smooth muscle cells themselves, which respond by contracting
- This is a major mechanism of autoregualtion of blood flow = an increase in transmural pressure, which would increase flow, causes muscle contraction, which tends to maintain flow by increasing resistance
- Conversely, a reduction in transmural pressure leads to vasodilation
What is the role of reactive hyperaemia?
- Reactive hyperaemia is the increase in blood flow that occurs after supply to a tissue has been temporarily interrupted.
- This enables resupply to ischaemic tissue as quickly a possible
- The myogenic response is the predominant mechanism for brief occlusions, dilating the downstream vessels in preparation for the return of blood flow
- In more prolonged occlusions, vasodilator metabolites accumulate and these play a significant role.
- Return of blood flow → myogenic vasoconstriction and washing away of metabolites, causing a exponential decay
Describe the role of vasoactive agents released from endothelial cells
- Endothelial cells secrete both vasoconstrictor and vasodilator agents
- Vasodilator agents include NO, stimulated in response to thrpombin, bradykinin, ADP ACh
- NO may be formed in response to shear stress. NO produced the relaxation of vascular smooth muscle through reduction in cytosolic Ca2+. Nitric oxide synthase is expressed in higher amounts in places of turbulent flow and easily damaged areas = defence mechanism
- Vasoconstriction is caused e.g. by endothelin I and is released in response to stretch, thrombin and adrenaline
- Release may be induced by the binding of various ligands to endothelial cells
How can circulating factors affect blood flow?
- Among these is adrenaline from the adrenal medulla → vasoconstriction in most organs, but vasodilation in skeletal muscle, myocardium and liver
- The peptide Angiotensin II produced by the kidney is a powerful vasoconstrictor = causes vasoconstriction at high concentrations by actibe directly on vascular sooth muscle, initiate the release of NA from sympathetic nerve terminals, and increasing central sympathetic drive in the brainstem. Also increases aldosterone secretion from the adrenal cortex which increases Na+ and therefore ECF volume and plasma volume, increasing cardiac output
Define autoregulation
The process that maintains a constant flow of blood to an organ despite changes in arterial pressure through local control mechanisms
What are the stages of hypertension?
Hypertension may be essential (95%) or secondary(5%) e.g. due to high renin
What are the consequences of hypertension?
Initially asymptomatic
- Heart has to do more work
• Hypertrophy of the left ventricle
• Earlier onset of heart failure
- Heart has a higher O2 demand
• Increased risk of myocardial ischaemia and infarction
- Damage to blood vessels
• Acceleration of atherosclerosis
• Aortic aneurysm & dissection of the aorta
• Stroke
• Damage to kidney
• Retinopathy
What determines venous return?
- Veins are thin walled and highly compliant, though there will be a venous tone owing to contraction of their smooth muscle
- The pressure in veins will be determined by the volume of blood they contain
- Depends on what flows in from the body & out by way of the heart.
What is central venous pressure?
- This is the pressure in the great veins – it is the pressure that fills the heart
- Depends on return from the body – effects of ‘muscle pump’, respiratory efforts are necessary to counteract the effects of gravity
Give 5 methods involved in the autoregulation of blood vessels
1. Vasodilator metabolites
2. Myogenic contraction
3. Circulating factors
4. Factors released from endothelial cells
5. Temperature
What is the mediastinum?
- The space between the two lungs and pleurae
- Contains all the structures of the chest except the lungs and pleurae
- Extends from the superior thoracic aperture to the diaphragm, and from the sternum to the vertebrae
- Mediastinum divided into superior and inferior parts, and the inferior part divided into anterior, middle and posterior parts
Describe the contents of the divisions of the mediastinum
- Superior mediastinum found between the transverse thoracic plane (sternal angle to T4-T5) to the thoracic inlet:
→ Thymus anteriorly
→ The great vessels in the middle
→ The oesophagus, trachea and thoracic duct posteriorly
- Inferior mediastinum between the transverse thoracic plane divided into:
→ Anterior inferior mediastinum = posterior to the sternum and anterior to the pericardium
• Inferior thymus
→ Middle mediastinum
• Heart and pericardium
• Great arteries
• Phrenic nerve
• Main bronchi
→ Posterior mediastinum
• Oesophagus
• Thoracic aorta
• Vertebral bodies
What is the pericardium? Describe its layers
- A fibroserous sac that covers the heart and the beginning of its great vessels
- Composed of an outer fibrous layer
- Inner serous part composed of 2 layers - a parietal pericardium close to the fibrous paricardium, and a visceral pericardium closest to the heart. Between these layers is secreted a layer of pericardial fluid
- The pericardium helps anchor the heart and helps allow the heart to beat without friction (using the pericardial fluid)
Describe the attachments of the pericardium
- Base fused with the central tendon of the diaphragm
- Fused with the tunica adventitia of the great vessels entering and leaving the heart
- Anterior joined to the sternum via sternopericardial ligaments
What are the 2 sinuses found in the pericardium?
- Formed by folding of the embryologial heart
- Transverse pericardial sinus is a recess within the pericardium, posterior to the aorta and the pulmonary trunk and anterior to the superior vena cava
- The oblique pericardial sinus is a blind recess formed by the inferior vena cava and pulmonary veins
Where is the base of the heart?
Located posteriorly and formed mainly by the left atrium
Where is the apex of the heart?
- Formed by the left ventricle and is posterior to the 5th intercostal space
What forms the sternocostal surface of the heart?
Mainly the right ventricle
What forms the diaphragmatic surface of the heart?
Mainly by the left ventricle, and part of the right ventricle
What forms the pulmonary surface of the heart?
Mainly the left ventricle
What makes up the borders of the anterior heart?
- Right = right atrium →venous side of the heart (SVC and IVC)
- Left = left ventricle and left auricle → arterial side of the heart (aortic arch, pulmonary artery)
- Inferior = mainly right ventricle, and small part of left ventricle
- Superior = right and left auricles
What is pericardial effusion?
- Passage of fluid from pericardial capillaries into the pericardial cavity, or an accumulation of pus
- As a result, the heart becomes compressed and unable to expand or fill full because the fibrous pericardium can only stretch a little. This reduces cardiac output.
- May also result from congestive heart failure = heart that fails to pump blood out at the same rate that it receives blood
What is cardiac tamponade?
- Heart compression
- May be caused by pericardial effusion or haemopericardium (e.g due to a myocardial infarction or stab wounds).
- Haemopericardium is more likely to be fatal because of the high pressure involved and the rapidity of the accumulation of fluids
- Potentially lethal as the heart volume is increasingly compromised by the fluid outside the heart but inside the pericardial cavity
- Treatment = pericardiocentesis → syringe at 15 degrees from surface of skin
Describe the features of the right atrium
- Has the right auricle = conical muscular pouch that projects from the chamber, increasing its capacity
- Has a smooth, thin-walled posterior part, onto which the SVC, IVC and coronary sinus (between the right AV orifice and the IVC orifice) empty
- Rough anterior wall composed of pectinate muscles
- Smooth and rough parts of the wall separated by a vertical ridge, the crista terminalis, internally (sulcus terminalis externally)
- Interarterial septim has the fossa ovalis
- Tricuspid valve to the right ventricle
Describe the features of the right ventricle
- Contains irregular muscular elevations = trabeculae carneae
- Thick muscular ridge, the supraventricular crest, separates the ridged muscular wall of the inflow part of the chamber from the smooth wall of the outflow part (conus arteriosus)
- Papillary muscles = 3 conical muscular projections which pull chordae tendinae, which are attached to the cusps of the tricuspid valve. This closes the valve and helps prevent regurgitation
- Septomarginal trabeculae (moderator band) is a curved muscular bundle that carries part of the right branch of the AV bundle
- Pulmonary valve
Describe the features of the left atrium
- Left muscular auricle which contains pectinate muscles
- Larger, smooth-walled part
- Valveless pairs of right and left pulmonary veins enter
- Thicker wall that the right atrium
- Left mitral valve
- Fossa ovalis with surrounding annulus ovalis (remnant of valve)
Describe the features of the left ventricle
- Walls 3 times as thick as right ventricle
- Walls covered with trabeculae carneae which are more numerous and finer than those on the right
- 2 papillary muscles, which are larger than the right, with cordae tendinae attached, to the aortic valve
- Aortic vestibule, leading to the aortic valve
Where do the coronary arteries arise?
- Left coronary artery arises from the left anterior cusp of the aortic valve
- Right coronary artery arises from the right anterior aortic sinus just above the right anterior cusp of the aortic valve
Describe the 3 tissue layers of the heart wall
- Epicardium aka visceral pericardium
- Myocardium = thickest layer and contains muscle cells which attach to the heart skeleton, providing a base for contraction. Atrial myocardium secretes ANP (atrial natriuretic peptide) when stretched, promoting salt and water excretion. Ventricular myocardium secretes BNP (brain natriuretic peptide) when stretched
- Endocardium = 3 layers. An outermost connective tissue layer (containing nerves, vessels and Purkinje fibres), an middle connective tissue layer, and a inner endothelium of flat endothelial cells
What is the heart skeleton?
- Consists of fibrocollagenous rings of dense connective tissue encircling the base of the aorta and pulmonary trunk and the atrioventricular openings
- The heart valves and muscles attach to these to form the base of muscle contraction
- Also electrically insulates the atria from the ventricles except along the interventricular septum, which contains the bundle of His
What is the most important point to remember about heart valves?
They are avascular so if bacteria invades the valves there will be little immune reaction and infective endocarditis may result. Also, serious problems healing
Describe 3 cardiac-specific radiographic views
1. Short axis
- Slices perpendicular to long axis of LV
- LV and RV chambers well seen
- Volume measurements
- Easy to see wall thickness

2. Horizontal long axis
- Perpendicular plane through vertical long axis
- 4 chamber view
- As seen from below looking upwards and see left and right
- Chamber size, septum, mitral and tricuspid valves well seen

3. Left ventricular outflow tract
- Through and perpendicular to plane of aortic valve
- Oblique coronal plane
- Thick wall LV, brachiocephalis trunk, common carotic artery → functional anatomy of heart
Describe the anatomical positions of the heart sounds and where you would listen to heart sounds
- Note that you listen to valves in the direction of the flow of blood from the valve
Describe the 2 pericardial sinuses
- Two sinuses:
1. Transverse sinus
- posterior to the pulmonary trunk and ascending aorta and anterior to the superior vena cava. Superior to the atria;
2. Oblique sinus of the pericardium
- posterior to the base of the heart, anterior to the oesophagus
What is this and what is its cause?
- GLobular heart shadow on CXR
- Heart loses shape due to pericardial effusion
- Pain worsens when sit forwards
- AXR shows large extra swelling of fluid within the pericardium of the heart
How can radiography be used to assess cardiac hypertrophy?
- Heart should occupy 50% of the maximum internal thoracic diameter on a standard PA erect view → if it is larger than this hypertrophy is present
- Cannot comment on heart size on AP view because magnification of the heart is seen
What is dextrocardia?
- Heart found on RHS
- Very rare = 1/20,000
- Usually associated with other situs invertus
Describe the path of the phrenic nerve in the mediastinum
- The right phrenic nerve travels down the SVC and across the LA to the diaphragm
- The left phrenic nerve travels more anteriorly, along ascending aorta and pulmonary trunk, to travel along the left ventricle to the diaphragm
Describe the 2 types of cardiac vavles
1. Semilunar vavles
- Passively opened and closed
- Pulmonary artery and aorita
- 3 cusps

2. Atrioventricular vavles
- Passively opened and closed
- Actively held closed by papillary muscles pulling on the chordae tendineae
What is there problem here?
- Calcification of the aortic valve → aortic stenosis and possible left sided hypertrophy
Label 1, 4 and 7
1 = Left anterior descending (anterior interventricular) artery
4 = Circumflex artery (NOT LAD)
7 = Left coronary artery
What is the problem here and how may it be treated?
- Coronary heart disease of right coronary artery
- Treatment
1. Coronary bypass graft (CABG = cabbage) = from internal thoracic artery or long saphenous vein
2. PTCA = coronary angioplasty → remodelling the artery through the skin
3. Stents = keeps the artery open
Describe the basic circulation of the heart
- The systemic circulation is in series with the pulmonary circulation
- Atria are thin-walled reservoir
- Ventricles are muscular pumping chambers
- Valves control the inflow and outflow of the ventricles
- The left mitral valve has only 2 cusps rather than 3 to better withstand the high pressure that it is under
- Pulmonary veins drain into the left atrium
- Left atrium drains into left ventricle through the mitral valve
- Left ventricle pumps out of the aorta through the aortic valve
- SVC and IVC return blood to the right atrium
- Right atrium flows into the right ventricle through the tricuspid valve
- Right ventricle flows into the pulmonary arteries through the pulmonary valve
Describe the mitral valve
- Papillary muscles are an integral part of the LV
- They help the mitral valve to close with their chordae tendineae to prevent regurgitation
- Consequenty, mitral repair is preferred to replacement as the muscle is useless otherwise → atrophy, and it is less thrombogenic
Describe the conduction of action potential through the heart
- Conduction of action potential:
1. Depolarization is initiated in the SA node
2. Depolarization spreads through adjacent atrial work cells causing atrial systole in both atria
3. At the AV node the wave of depolarization is delayed by approximately 0.1s so that the atria can contract fully
4. Conduction continues through the bundle of His and its left and right bundle pathways. These are very fast conduction pathways
5. Numerous subendocardial Purkinje fibres distribute the impulse to the work cells in the endocardium
6. Adjacent work cells then continue the spread to the epicardiu to depolarise the whole ventricle
What is the sinuatrial node?
- All parts of the heart a capable of causing a heart beat
- The sinoatrial node has the highest intrinsic firing rate, and therefore controls heart rate
- The SA node is located in the posterior wall of the right atrium.
- The SA node is the cardiac pacemaker and is responsible for initiating the depolarization and subsequent contraction of the whole heart
What is a chronotropic agent?
- An agent that increases (positive chronotrope) or decreases (negative chronotrope) the heart rate
What is an inotropic agent?
- An agent that increases (positive inotrope) or decreases (negative inotrope) the force of contaction
What is heart rate and what is its typical value?
- Beats per minute
- Typically 60-70bpm
What is stroke volume and giveits typical value?
- Volume (ml) ejected by each ventricle per heart beat
- Typically ~70ml
What is cardiac output and give its typical value?
- Cardiac output is the product of heart rate and stroke volume
- Typically ~ 5l/min
Define systole and diastole
- The period when the ventricles relax is called diastole and takes ~700ms
- The period when the ventricles cotract is called systole and takes ~300ms
- To increase the heart rate the length of diastole (but not systole) becomes shorter
Describe ventricular filling
- Within diastole
- g,a
- Lasts 0.5s
- AV valves are open and arterial valves are closed
- Ventricular pressure falls, then slowly rises and ventricular volume increases
- The atria and ventricles are relexed initially and there is passive filling of the ventricles
- The volume continues until a neutral ventricular volume is reached
- Further filling, driven by venous pressure, causes the ventricle to distend, causing the ventricular pressure to rise
- Contraction of the atria further increases the filling of the ventricles - but really only 'tops-up' what is already there (only 15-20% of ventricular filling at rest)
- The volume now in the ventricle is termed the end-diastolic volume
Describe isovolumetric contraction of the heart
- During systole
- Lasts 0.05s
- b
- AV valves are closed and arterial valves are closed
- Rapid rise in ventricular pressure
- Ventricular volume is constant
- The contraction of the ventricles increases ventricular pressure
- Ventricular pressure rises above arterial pressure, thereby closing the AV valves and creating a closed chamber
- As contraction proceeds, wall tension increases, causing a rapid rise in ventricular pressure
- The rise of pressure is a measure of cardiac contractility
Describe ejection of the cardiac cycle
- Duration = 0.3 seconds
- c & d (not the aortic pressure should be lower than the ventricular pressure as blood is moving downhill and a pressure gradient is needed)
- AV valves closed
- Arterial valves open
- Ventricular pressure rises, thanslowly falls
- Ventricular volume decreases
- Ventricular pressure rises aboe arterial pressure, opening the arterial valves
- This causes a rapid initial rise in the arterial pressure, and then the pressure starts to fall as the contraction fades
- The momentum of the blood prevents immediate valve closure, even when the ventricular pressure falls below arterial pressure
- Eventually the arterial valves close, creating a brief dicrotic notch as the walls of the vessels elastically return
- Note: the ventricle does not empty completely - at rest it remains 50% full, which can be used to increase stroke volume if necessary
Describe isovolumetric contraction of the heart
- During systole
- Lasts 0.05s
- b
- AV valves are closed and arterial valves are closed
- Rapid rise in ventricular pressure
- Ventricular volume is constant
- The contraction of the ventricles increases ventricular pressure
- Ventricular pressure rises above arterial pressure, thereby closing the AV valves and creating a closed chamber
- As contraction proceeds, wall tension increases, causing a rapid rise in ventricular pressure
- The rise of pressure is a measure of cardiac contractility
Describe ejection of the cardiac cycle
- Lasts 0.3s
- AV valves closed
- Arterial valves open
- c & d
- Ventricular pressure rises, than slowly falls
- Ventricular volume decreases
- Ventricular pressure rises above arerial pressure, opening the arterial valves
- This causes a rapid initial rise in arterial pressire, and then the pressure starts to fall as the contraction fades
- The momentum of the blood prevents immediate closure of the valve, even when the ventricular pressure falls below arterial pressure
- Eventually the arterial valves close, which creates the brief rise in arterial pressure called the dicrotic notch, as the elastic walls of the arteries return
- Note: the ventricle does not empty completely. It usually remains 50% full, and can be used to increase heart value where necessary
Describe the isovolumetric relaxation of the cardiac cycle
- Lasts 0.08s
- AV valves closed
- Arterial valves closed
- e
- Ventricular pressure rapidly falls
- Ventricular volume is constant
- The relaxation of sarcomeres plus collagen recoil drops the ventricular pressure
- When ventricular pressure falls below atrial pressure, the AV valve open, leading to filling
Describe the sounds of the heart and why they occur
- 4 possible herat sounds
- S1 = mitral and tricuspid closure
- S2 = aortic and pulmonary valve closure
• These valves don't close at exactly the same time and therefore can be split (this can be heard better when the patient inhales)
- S3 = passive LV filling in early diastole. High blood velocity causes sound from blood turbulance
- S4 = PATHOLOGICAL active (atrial kick) LV filling in late diastole. Found in individuals with impaired ventricular filling e.g. hypoertrohpy, or when a high cardiac output is required, as atrial contraction is needed to produce a high enough cardiac output
What is fibrillation?
- Fibrillation is chaotic electrical and mechanical activity due to errors in the spread of the heart beat
- The pumping action of the affected chamber is lost

- Atrial fibrillation reduces efficiency of the heart but does not cause a serious problem for cardiac output in the absence of other heart disease
• Blood may be more likely to be trapped in the atrium and clot (thromboembolism), increasing the risk of stroke
• A rippling effect of the muscle occurs, which does not contribute to ventricular filling
• Ventricular activity is affected, producing a characteristic 'irregularly irregular' pulse in rate and volume
• Commonly caused by mitral valve disease, ischaemic heart disease, thyrotoxicosis, hypertension and alcohol

- Ventricular fibrillation results in complete loss of cardiac output and is fatal within minutes unless corrected (electrical defibrillation)
Describe how right atrial waveform can be assessed
- JVP is the best way of assessment
- JVP indicates right heart pressure, and therefore if raised can be indicative of disease e.g. right heart failure of SVC obstruction
- The waveform can also be observe if the venous pressure is normal, which also can be indicative of various diseases e.g. atrial fibrillation
What is pulmonary capillary wedge and what does it measure?
- Push a catheter through the venal side into the right ventricle and then into the pulmonary artery. As you continue to push it, it will become lodged as it's so small, stopping the flow of blood
- This allows a measurement of left atrial pressure (as blood it returning to the LA)
Describe the differences in pressures in different chambers of the heart during the cardiac cycle
Describe where you would auscultate for the heart
What is a murmur?
- Turbulent flow through the heart, which is audible with the stethoscope
- May be caused by:
• High cardiac output (normal heart)
• Leaking valves
• Narrowed valves
• Abnormal connections between cardiac chambers
Describe the changes in heart sounds brought about for aortic stenosis
- Increased resistance of flow of the aortic valve (which has been narrowed) and turbulent flow through it
- Increases ventricular work
- This increase of work is an example of pressure overload and is also seen in hypertension
- Causes a murmur between S1 and S2 but a normal diastole
Describe the differences in sounds of the heart in aortic regurgitation
- Systole is normal
- Early diastolic murmur which tails off, so that diastole seems shorter
- Listen for on the left hand side and blood will be flowing in the wrong direction
Describe the differences in sounds of the heart in mitral regurgitation
- Systolic heart sounds are not completely separate due to regurgitation murmur
- Diastole normal
Describe the differences in sounds of the heart in mitral stenosis
- Mid to late diastolic murmur
- Systole is normal, and slight gap between S2 and it beginning
What is hypertrophy of the heart and why might it occur?
- Increase in the size of the heart
- Heart muscle responds toany kind of long-term stres (physiological or pathological) by undergoing hypoertrophy
- Physiologically may be an adaptive response in athletes e.g. cycling, rowing, weightlifting
- May also be caused by aortic stenosis and after an MI
- Concentric hypertrophy (increase in muscle thickness inwards but not of overall heart) may cause a pressure overload
- Eccentric hypertrophy (increase in lumen and overall size of heart) may cause volume overload, and therefore the apex beat may appear to move around
Describe the formation of the heart into a 4 segmented tube
- The cardiogenic region is a horse-shoe shaped region derived from the splanchnopleuric mesoderm by a process called vasculogenesis (day 19)
- A network of blood vessels and the blood cells inside them, begins to form in the mesoderm during the 3rd week of development
- Gradually one vessel on each side becomes larger than the rest of the network. These vessels are the 2 endocardial tubes
- Folding of the embryo draws the endocardial tubes together in the midline and positions them ventral to the future head region. The 2 tubes fuse and the 1st primitive heart is formed
- Cardiac muscle differentiates in its wall and it begins to beat around day 21
- Blood enters the heart at the posterior end from the developing network of veins and is pumped out anterior into the arteries, thus establishing a circulation
- As the heart enlarges it changes from a simple tube to one with 4 segments - from posterior to anterior:
1. Sinus venosus
2. Atrium
3. Ventricle
4. Truncus arteriosus
The blood flow into the sinus venosus comes from which 3 pairs of vessels?
1. Cardinal veins that drain the embryo proper
2. Vitelline veins from the yolk sac
3. Umbilical veins from the placenta
- The umbilical and vitelline veins traverse the liver, which forms within the tissue of the septum transversum
Describe the folding of the heart
- A cavity, the pericardial cavity forms around the heart
- As the heart grows longer it bends into a loop in order to accomodate to the size of the pericardial cavity
- The sinus venosus and atrium come to lie posterior to the ventricle and truncus arteriosus
Describe the formation of the mature ventricles
- The superior, inferior, right and left cusions form around the atrioventricular canal
- At the same time the ventricular septum begins to grow up towards the cushions to divide the single ventricle
- Dorsal and ventral endocardial cushions fuse in the middle of the AV canal, forming the AV septum which divides the canal into rigt and left AV openings. The also form the mitral and tricuspid valves
- Also, neural crest cells that form at the level of the 4th and 6th aortic arches populate the forming trucal cushions
- These form the conotruncal cushions and the pulmonary and aortic trunks
- The conotruncal cushions fuse to form the aorticopulmonary septum
- Further along the outflow tract, these cushions are more dorsal and ventral to one another. This change in position is indicative of the spiraling of the aorticopulmonary septum, aorta and pulmonary artery
- Fusion of the outflow tract cushions resuts in the separation of blood flow to their correct constituent parts
Describe the formation of the mature atria
1. Septum primum grows down from the roof of the common atrium towards the fused endocardial cushions. The ostium primum is the gap between the septum primum and the endocardial cushions (it does not grow all the way down)
2. Septum secundum appears in the roof of the common atrium on the right side of septum primum. The ostium secundum is formed by the rupture of the upper part of septum primum. Ostium primum is closed by the fusion of the septum primum with the AV septum
3. Foramen ovale is the oblique passage between septum primum and septum secundum. Septum primum is a moveable septum, whereas septum secundum is a rigid septum. During the foetal period, septum primum acts like a valve of foramen ovale, letting blood floew from right atrium (high pressure side) to left atrium (low pressure side). This is important as foetal blood flow must still get through from right to left atria.
4. At birth the pressure in the left atrium increases and pushes the septum primum to septum secundum, closing the foramen ovale and forming the interatrial septum. This is a functional closure - the anatomical closure takes 3 months, and may never truely complete. The lowere margin of the septum secundum forms the annulus fossa ovalis. Septum primum forms the fossa ovalis
How does cigarette smoking cause heart disease?
- Nicotine increases the amount of work that the heart has to do
- Chemicals from the cigarettes also attack and damage endothelium which is the first step in heart disease
→ makes it easier to get heart disease
Why is the arterial blood supply at such a high pressure compared with the venous blood supply?
- High pressure needed to overcome systemic resistance
- Also need to raise the blood to the level of the brain, requiring considerable force
What is the average stroke volume at rest?
About 70ml of blood per beat
What is the typical cardiac output at rest?
Approx. 5 litres of blood per minute
What are the roles of the systemic and pulmonary circulations?
- Systemic = flow serves to supply cells with their metabolic needs by exchange between the blood and the metabolising cells
- The pulmonary circulation has the role of acquiring oxygen and excreting carbon dioxide in appropriate amounts, by exchange between blood and the gas in the lungs.
How does the main part of exchange occur across capillaries?
Via diffusion
What factors will determine the rate of transfor of water and solute through the capillary wall and give the equation that combines these
1. The area (A) available for exchange - essentially the capillary density
2. Permeability (P)
→ How readily the substance moves through the endothelium
→ The path length to or from the metabolising cell.
3. The concentration gradient (Ci-Co) down which movement occurs

Summarised by Fick's Law:
J = P.A.(Ci-Co)
Describe how the permeability of the capillary wall may be determined by the nature of the molecules involved
Depends largely on the molecules involved:
- Lipid soluble molecules, which include O2 and CO2, diffuse easily through capillary cell membranes
- Hydrophilic molecules travel through pores, often through a paracelular route. The larger the molecule the greater the resistance to transfer
- Molecules whose molecular mass >60kD are not transferred and many plasma proteins are retained in the circulation - important in the equilibrium between plasma and the interstitial fluid
Describe how path length may be important in determining the rate of diffusion of molecules through the capillary walls
- Substances diffusing out of capillary beds must traverse a path through interstitial fluid between the capillary wall and the metabolising cell
- The length depends on the capillary density
- An increase length will mean that the molecules must travel further and thus may not reach necessary cells
- This is particularly important in oedema = increase volume of interstitial fluid jeopardises the supply of metabolites to cells and can cause necrosis
Give 2 factors that may affect the size of the gradient of molecules across the capillary wall
1. How rapidly the tissues are using the substances being delivered in the blood = metabolic rate
2. How rapidly the blood flows through the tissues = blood flow
Why is rate of flow of blood important in defining rate of capillary transfer?
- The rate of flow must be adjusted to optimise delivery to and removal of substances from tissues
- If the flow is too rapid, there may not be time for exchange
- If the flow is too slow, the concentration gradient will be dissipated as transfer will largely occur at the beginning of the capillary so that there will be no gradient further down the capillary
- For many small, highly diffusible substances, the gradient is dissipated along the whole length of the capillary
- Transfer then becomes flow limited
What is the most important factor in determining the rate of transfer in capillaries?
- Concentration gradient
→ the delivery of many metabolically important materials is limited by the rate of flow
→ Metabolic need is a major physiological mechanism for regulating flow and optimising transfer (i.e. maintain the right flow of blood for the prevailing level of metabolic activity)
- Generally, area, and for small molecules, diffusion resistance, are not limiting factors.
What are the 2 major roles of capillaries?
1. Permits the exchange of nutrients and metabolites between the blood stream and metabolising tissues by diffusion
2. Determines the equilibrium between the plasma and the interstitial fluid
What are the forces governing the development of the equilibrium of interstitial fluid and plasma across the capillary bed?
- Governed by Starling forces
- Loss of fluid from the plasma due to hydrostatic pressure is opposed by reabsorption of fluid into plasma, owing to colloid osmotic pressure (oncotic pressure)
- Hydrostatic pressure of the blood at the arteriolar end is 37 mmHg
- Hydrostatic pressure of the blood at the venous end is 17 mmHg
- Hydrostatic pressure of the interstitial fluid is 0 mmHg, so that hydrostatic pressure forces fluid out of the plasma across capillary walls
- Impermeance of plasma proteins generates an oncotic pressure of 25 mmHg, which draws fluid back into the capillaries from the interstitial spaces
- The filtration pressure = hydrostatic pressure - oncotic pressure
- At the arterial end, the hydrostatic pressure is greater that the oncotic pressure, and there is net filtration
- At the veonus end, the oncotic pressure is greater than the hydrostatic pressure, and there is net reabsorption
- In the middle an equilibrium is met where these are balanced
Give 3 different causes that may disrupt the equilibrium between the interstitial fluid and the plasma
1. Increase in hydrostatic pressure will force fluid into the interstitial space. Oedema will result if there is an accumulation of fluid in this space
2. In liver disease, renal disease or severe starvation, plasma protein levels fall, decreasing oncotic pressure. This will also drive fluid into the interstitium , leading to oedema
- Capillaries become more permeable to protein when damaged, causing a decrease in oncotic pressure, leading to oedema e.g. in the swelling of a sprained joint
Describe capillary transport mechanisms
- Exchange of solutes generally occurs by diffusion down concentration gradients
- Processes involved include:
→ diffusion through the endothelial cell membrane = lipid-soluble substances e.g. O2 and CO2
→ Diffusion through the pores and fenestrations in the cell membrane = water soluble substances e.g. water, glucose, amino acids
→ Active transport by transcytotic vesicles = some proteins
Describe the distribution of blood flow to the brain, heart, kidney, gut, skeletal muscle and skin
- Brain = the metabolic needs of the brain are constant and can be met by a flow of 0.5ml/min/g. The brain is extremely intolerant of flow interruption
- Heart = at rest the heart needs 0.9ml/min/g but if it has to work hard this can increase four-fold. The heart is extremely intolerant of inadequate flow
- Kidney = requires a high constant blood flow to maintain its function, though most flow is not nutritive
- Gut (and liver) = at rest receives 1ml/min/g. Digestion of a meal generates a substantial increase in flow. Short term flow reduction tolerable
- Skeletal muscle = metabolic needs very variable. At rest flow needs ~0.03ml/min/g, which may rise up to 6.0ml/min/g in exercise, but this may not reach metabolic needs. Muscles can survive a degree of anabolic metabolism.
- Skin = not metabolically very active and may be supported by 0.03ml/min/g, though flow may increase to 0.1ml/min/g for thermoregulation
Describe the 3 aims of the cardiovascular system
1. Deliver between 5 and 25 l/min of blood to the body
2. Maintain a blood flow of 750 ml/min to the brain at all times
3. Maintain blood flow to the heart and kidney at all times
Describe 4 ways in which the cardiovascular system can carry out its specifications
1. Needs a pump to create flow = the heart. Two sides of the heart must put out the same volume of blood, virtually beat for beat
2. Distribution vessels = arteries. High arterial pressure and low venous pressure allows distributions
3. Flow control = the output of the pump (the cardiac output) must be distributed by restricting flow to those parts of the body which are easy to perfuse so as to drive blood to those, often vulnerable, parts which are not so easy to get blood to. Flow control is via resistance vessels:
- arterioles and arteries, which can be altered by metabolic factors, and neural and humoral factors
- Precapillary sphincters, which can shut down or open parts of the capillary bed and therefore alter the effective density
4. The ability to cope with changes in the cardiac output = requires capacitance in the system - a store of blood that can be called upon to cope with temporary imbalances between the amount of blood returning to the heart and the amount it is required to pump out. This store is in the veins.
Describe the distribution of blood volume in the body
Blood volume is ~5L. Distrubuted as:
- 11% in the arteries and arterioles
- 5% in the capillaries
- 17% in the heart and lungs
- 67% in the veins
What are the 4 classifications of blood vessels and name the blood vessels in each type
1. Conductance
- Low resistance vessels
- Large arteries with predominantly elastic walls to smooth out pulsatile flow
- Role is delivering blood to more distal vessels, although they may have a small resistance role

2. Resistance
- Terminal arteries and arterioles
- Act to control local blood flow
- Muscular walls
- Dilation of these vessels lowers resistance and increases blood flow
- Constriction of these vessels increases resistance and decreases blood flow
- Influence exchange vessels by governing the flow that reaches them

3. Exchange
- Capillaries
- Thin walled for exchange
- Optimises their function, which is to allow rapid transfer between blood and tissues
- Also contribute some resistance to flow

4. Capacitance
- Thin walled and low-resistance
- Venules and veins
- Variable reservoir of blood volume and contain almost 2/3 of the volume
- Innervated by venoconstrictor fibres which, when stimulated, can displace blood back to the heart
Describe the basic structure of a blood vessel
1. Lumen
2. Tunica intima:
- Endothelium
- Supporting connective tissue (arterial disease develops here due to endothelial damage)
3. Tunica media
- Elastic tissue = alters resistance and stretch
- Smooth muscle = regulates width of the lumen
4. Tunica adventitia
- Principally collagen
Describe a typical elastic artery
- Walls expand slightly with each heartbeat
- Large amount of elastic and muscular tissue throughout the tunica media
- Media thicker than the adventitia
Describe the histology of a muscular artery
- Has a prominent muscular tunica media, with an internal and external elastic laminae
- Less resistant to stretch as less elastic tissue
Describe a typical atheroma
- If the endothelium is damaged an athethromatous plaque may develop in the tunica intima
- The tunica intima may grow so thick that a thrombus may be caused. This may break off and cause a heart attack, stroke or pulmonary embolism
Describe factors involved in the vasoconstriction and vasodilation of arteries and arterioles
- Local metabolites (including O2 and CO2)
- Nervous action - sympathetic nerve fibres
- Circulating vasoactive hormones
- factors secreted by endothelial cells
- mechanical factors e.g. stretch of vessel wall
Name 3 ways that flow can be reduced to the capillary bed
1. Constriction of metarterioles
2. Use precapillary sphincters to close off parts of the bed
3. Arteriovenous anastomoses = not capillaries as have smooth muscle and do not take part in gaseous exchange. Very important in temperature regulation, as shunts the blood straight into the venous system without any loss of resistance to flow
Describe the histology of capillaries
- Most capillaries are thin walled, with a single layer (sometimes 2 layers) of endothelial cells on a basement membrane
- No tunica media so no smooth muscle nor elastic tissue
- The arrangement of endothelial cells determines the permeability of capillaries
- Surrounding periocytes may have a muscular function, and may be involved in angiogenesis
Describe the classification of capillaries
1. Continuous
→ endothelial cells joined via tight junctions
→ prevents the leakage of proteins
→ found in most tissues
2. Fenestrated
→ Found in exocrine glands
→ Large windows which are covered by a mesh of fibres so that molecules larger than 70kD cannot get through
→ Capillaries more permeable to water, but prevents leakage of proteins
3. Discontinous
→ No joining of cells
→ Intracellular gaps/pores
→ Found particularly in the liver and spleen where proteins are secreted into the blood

Note: Endothelial cells junctions in the brain have a complex arrangement of fibres so that they are only permeable to hydrophilic molecules. This comprises the blood-brain barrier, which tightly controls the neuronal environment
Describe the molecules that are transferred through capillary walls
- Transfer occurs by way of cellular and paracellular routes
- O2 and CO2 readily transferred through the cells
- Water, glucose and electrolytes principally through paracellular routes = intercellular junctions, fenestrae in fenestrated capillaries
- Protein transfer is limited = intercellular gaps in discontinuous capillaries or cellular transfer in vesicles
How to lymphatics help regulate extracellular fluid?
- Lymphatics act by mopping up any excess filtrate and returning it to the main circulatory system (LSV). They also carry foreign antigens from the blood to cells of the immune system located in the lymph nodes
- Lymphatics start as blind ended sacs = terminal lymphatics which are found around capillary beds
- Terminal lymphatics have large endothelial cell junctions anre so they are permeable to plasma proteins and other large molecules
- Lymph capillaries join together to form collecting vessels, which may contain valves to prevent backflow. They also have smooth muscle in their walls
- Afferent vessels drain into lymph nodes, where the fluid is presented to the immune system and some lymph may enter the blood
- Efferent vessels leave the lymph node and enter the cisterna chyli, which acts as a reservoir for chylomicrons from the gut
- Eventually the lymph drains into the large thoracic duct, draining into the LSV
Describe the structure of veins and venules
- Veins and venules have a very thin tunica media, but a larger tunica adventitia than arteries and arterioles
- Post-capillary venules have no tunica media, similar to capillaries
- Like muscular arteries, small and medium-sized veins have internal and external elastic layers on either side of a muscular layer, which makes up the tunica media. Large veins have a larger amount of both elastic tissue and smooth muscle
- Veins contain valves, which aid in the transport of blood back to the heart
How are large blood vessels and nerves supplied with blood?
- Larger vessels need their own blood supply as nutrients are unable to diffuse across the many layers of cells, and deoxygenated blood is already low in nutrients. Instead they are supplied with small vessels called vasa vasorum
- Similarly, nerves are supplied by small vessels called vasa nervorum. In certain conditions, such as diabetes, these vessels are targeted, causing damaged nerves and neuropathy. The neuropathy then predisposes to subsequent joint damage and ulceration
What is the autonomic nervous system?
- Plays a major role in homeostasis and in regulation of physiological functions not under conscious control
Describe the divisions of the autonomic nervous system
- The autonomic nervous system and its divisions are defined anatomically
- Autonomic nerve fibres are part of the paripheral nervous system
- Autonomic fibres are efferent or motor (AKA visceral efferents) NOT afferent
- There are 2 divisions:
1. Symphathetic nerve fibres
- Arise from the thoracic and lumbar segments (T1 to L2) of the spinal cord = outflow is thoraco-lumbar
2. Parasympathetic nerve fibres
- Arise from certain cranial nerves (III, VII, IX and X) and from sacral segments S2-S4 of the spinal cord = outflow is cranio-sacral
Describe the distribution of sympathetic fibres
- Often distributed in spinal nerves
- Usually in spinal cord segments T1-L2
- Visceral afferent fibre enters spinal cord through dorsal horn and synapses
- Sympathetic efferent fibre given off from ventral horn into spinal nerve
- Sympathetic preganglionic fibres leave spinal nerve to synapse at sympathetic ganglia found on the sides of vertebral bodies between T1 and L2
- Some fibres may branch to synapse in ganglia further up or down the vertebral column → sympathetic chain interconnecting sympathetic ganglia
- Sympathetic post-ganglionic fibres rejoin the spinal nerves for distribution

- This contrasts with that of somatic nerves providing efferents to skeletal muscles which do not synapse (but somatic afferent fibres do at the dorsal root ganglion)
Briefly describe how nerves act
- Nerves act by releasing a transmitter, which must bind to a receptor on their target tissue
- In some cases, receptors are ion channels opened by ligand-binding:
• Nerve terminal releases transmitter in response to action potentials
• Transmitter binds to receptor on target cells
• Rapid but simple → transfer of impulse changing excitability
- In other cases, receptors are linked to G-proteins whose activation triggers a cascade of reactions in the cell
• Relatively slow series or reactions but can have subtle cellular effects and are amplifiable
What are the 2 principle transmitters of the ANS? What receptors do they act on?
1. Acetylcholine
2. Noradrenaline (norepinephrine) = a catecholamine
- Somatic efferent fibres release ACh which acts on nicotinic receptons at the NMJ

- Both parasympathetic and sympathetic branches of the ANS release acetylcholine from their pre-ganglionic fibres. This acts on (nicotinic) receptors on ganglionic cell bodies
- Most (but not all) post-ganglionic parasympatheic fibres also release ACh, which usually acts on the muscarinic type of adrenergic receptors
- Most (but not all) post-ganglionic sympathetic fibres release noradrenaline. Different effector organs have different receptor types for noradrenaline but there are 2 broad types:
1. α-receptors
2. β-receptors
Each is subdivided according to responses to different drugs
Describe ACh receptors and the signalling pathways they use
- Ach acts acts at cholinergic receptors
- Two types:
1. Nicotinic
- E.g. at autonomic ganglia
- ligand-gated ion channels
2. Muscarinic
- E.g. at post-ganglionic sites
- G-protein coupled receptors linked to signalling cascades
- Work either by:
• Generation of IP3 (causing Ca2+ release) and DAG (activates PKC)
• Inhibition of AC causing decreased cAMP and thus decreased activity of PKA
Describe noradrenaline and adrenaline receptors and the signalling pathways they use
- Adrenaline and noradrenaline acts at adrenoceptors
- 2 major types:
• Both types are G-protein coupled, but couple to different signalling pathways in cells
1. α-receptor linked to the activation of PLC forming IP3 and DAG and releasing calcium
2. β-receptor linked to activation of AC causing increased cAMP and increased PKA activity
Give 2 examples of other transmitters that ACh and NA that may be involved in the ANS
Other transmitters often involved as co-transmitters
1. ATP from sympathetic postganglionics
2. NO from parasympathetic postganglionics
Also various peptides
Describe the functions of the ANS
- Essential role in homeostasis = control of the internal environment
- May be dual innervation by both divisions, though the sympathetic has wider innervation
- Sympathetic and parasympathetic may have opposing influences
- Fright, flight or fight responses are sympathetic
Describe the length of sympathetic and parasympathetic nerve fibres
- Sympathetic preganglionic fibres are short and postganglionic fibres are long. However, some ganglia are located in the neck and abdomen and these have longer pre-ganglionic fibres
- Parasympathetic preganglionic fibres tend to be long and postgnaglionic fibres tend to be short. However, some ganglia are in the neck and abdomen and are further awat from their target organs
What is the role of the adrenal medulla in the ANS?
- Part of the sympathetic nervous system
- Preganglioic fibres run to the adrenal medulla, which is made up of modified postganglionic cells known as chromaffin cells
- These cells secrete adrenaline (and noradrenaline) into the blood stream
- Circulating adrenaline will also act upon receptors in the tissues, producing a more generalised effect
Give 5 examples of antagonistic sympathetic and parasympathetic activity
1. Pupil of eye: SY = dilatation, PS = constriction
2. Airways: SY = dilatation (note through action of circulating catecholamines on β2-receptors), PS = constriction
3. Blood vessels of erectile tissue: SY = constriction, PS = dilatation
4. GI motility: SY = reduced, PS = increased
5. GI sphincter: SY = constriction, PS = dilatation
Give an example of synergistic sympathetic and parasympathetic activity
Salivary glands: Sympathetic increases viscous secretion, parasympathetic increases serous secretion
Give 6 examples of systems where only one part of the ANS acts
1. GI secretion = PS stimulates serous secretion
2. Adipose tissue = SY stimulates lipolysis
3. Liver = SY stimulates glycogenolysis and gluconeogenesis
4. Kidney = SY stimulates renin secretion
5. Sweat glands = SY stimulates secretion (using ACh, muscarinic)
6. Male internal genitalia = SY stimulates seminal emission
What is the autonomic innervation to the heart?
- Parasympathetic = Vagus
- Sympathetic = inputs from T1-T4 and the inferior, middle and superior cervical ganglia, forming the cardiac plexus
Describe 3 chronotropic effects on the heart by the ANS
- Chronotropic effects = change the speed of the heart
- Sympathetic receptors = β1
- Parasympathetic receptors = M2
1. Sinoatrial node: SY increases rate; PS decreases rate
2. Atrioventricular node: SY increases autorhythmicity and reduced delay at the AVN, PS reduces autorhythmicity and increases delay at the AVN
3. Ventricle: SY raises automaticity, PS has no innervation
Describe 2 inotropic effects on the heart by the ANS
- Inotropic = increases contractility
- Sympathetic receptors = β1
- Parasympathetic receptors = M2
1. Atria = SY increases contratility, PS decreases contractility
2. Ventricle = SY increases contractility, PS no effect
Describe the regulation of blood vessel diameter by the autonomic nervous system
- Predominantly through sympathetic division
- Acts to alters the contractility of smooth muscle in the tunica media of blood vessels
- Both arteries (especially arterioles) and veins are affected
- Constant supply of sympathetic innervation to vessels = vasomotor tone
- Action potentials release NA from varicosities in sympathetic nerve endings. These activate the production of IP3 which releases Ca2+ from IC stores
- Vasoconstriction is caused by increasing the frequency of action potentials, causing increased amounts of released NA, causing increased contraction. This increases the blood pressure and decreases the flow of blood through the capillary bed to the organ
- Vasodilation is caused by reducing the frequency of action potentials, reducing the output of NA and therefore reduced contraction. This will decrease the peripheral resistance and blood pressure and increase the flow of blood through the capillary beds to the organs
- In most blood vessels circulating adrenaline will also constrict through binding to α1 receptors.
- This is important in vasoconstriction response to circulating or injected adrenaline, which causes widespread vasoconstriction at therapeutic doses e.g. in anaphylaxis
- Blood vessels of skeletal muscle have both α1 and β2 receptors. β2 receptors have a vasodilator action and have a higher affinity for adrenaline than noradrenaline
- This is important in regulating blood flow during exercise (as adrenaline levels will only be high enough to stimulate β2 receptors here)
- PS acts only on specialised blood vessels, though its stimulating action on organs such as the gut is associlated with the release of mediators which may produce dramatic vasodilation
Give 2 other circulating factors other than adrenaline and noradrenaline that help regulate blood vessel diameter
1. Angiotensin II
2. Vasopressin
- Both act as vasoconstrictors
Describe the process of maintenance of blood pressure
1. Baroreceptors in the carotid sinus and aortic arch measure bp and will fire more often at high pressure
2. Afferent sent to medulla oblongata, the vasomotor centre of the brain, which compares pressure to set point
3. Efferents sent out to heart and blood vessel to adjust blood pressure
Describe the changes that can be implemented by the ANS to correct blood pressure
- BP = CO x TPR
- Heart = changes of rate (PS and SY) and contractility (SY)
- Veins = changes of diameter of veins altering amount of blood held in veins (SY)
- Arterioles = changes of vasomotor tone (SY)
What is vasomotor tone?
- There is constant activity in the sympathetic nervous system, the sympathetic vasomotor tone, tending to make arteriolar smooth muscle contract.
- The tone varies from organ to organ as does the magnitude of the effect of sympathetic innervation.
- In skin, for example, vasomotor tone is normally high, so arterioles, pre-capillary sphincters and arterio-venous anastomosis are generally shut down. Large changes in skin blood flow are produced by variation in sympathetic outflow, usually for the purposes of thermoregulation.
- In skeletal muscles vasomotor tone is high at rest, but is reduced in exercise when it is also antagonised both by local release of vasodilator metabolites and by hormones.
- In the gut vasomotor activity is high until a meal is consumed, when it is antagonised by various vasodilator substances produced in gut tissue.
- The circulation to the brain on the other hand is virtually unaffected by sympathetic activity.
- Sympathetic outflow to blood vessels is controlled from the hindbrain - via the 'vasomotor' centres in the medulla oblongata.
- Sympathetic activity also produces veno-constriction which is contraction of smooth muscle in the walls of veins. This tends to increase venous pressure and force more blood back towards the heart.
Describe the divisions of congenital heart disease that you may see in an adult
Can be divided into 2 broad categories:
1. Acyanotic
May have:
• 2 ventricles
→ LV systemic disease
◘ Coarctation
◘ Most septal defects
◘ Aortic valve disease
◘ Repaired Fallot
→ RV systemic disease
◘ Corrected transposition of heart vessels
◘ Post Mustard
• 1 ventricle
◘ Fontan
2. Cyanotic
May have:
• Normal / low Pulmonary Artery pressure
◘ 50-60 different variations
• High PA pressure
◘ Eisenmenger syndrome
Describe aortic coarctation
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
• Narrowing of the descending aorta.
• Almost always located at the junction of the distal aortic arch and the descending aorta - just below the origin of the subclavian artery → radio-femoral delay as blood easily gets to arms but struggles to descend to the legs (if narrowing is before the origin of the subclavian artery there will be a radio-radial delay as blood will easily get down the right arm through the brachiocephalic, but struggle to get down the left subclavian
• Two types:
→ Localised stenosis = caused by a shelf-like infolding of the posterior wall of the aortic lumen opposite. Shelf is opposite to the ductus arteriosus, so that when the duct closes fibroductal cartilage can surroud the aorta and cause luminal obstruction
→ Longer hypoplastic segment = diffuse form involving the aortic arch or aorta distal to the origin of the SC artery

2. Genetics
• Makes up 5-8% Congital Heart Disease (CHD) and is almost doubly more common in males
• Cause is unknown
• Simple = in isolation
• Complex = associated with
→ bicuspid aortic valve
→ VSD
→ Mitral valve abnormalities
→ Intracranial aneurysms
= Important to look for a secondary abnormality

3. Presentation
• Severe coarctation commonly presents in infancy or after the 2nd or 3rd decade of life due to the consequences of heart defects associated with it
• In adults: may have arterial hypertension or an ejection systolic murmur due to turbulent flow (heard at the back)
• Patients are often asymptomatic

4. Management
• Often surgical
• Remove stenodid and stress and strain across the aorta as there is high pressure at the point of narrowing → high risk of dissection or rupture
• Maintain aortic patency
• Surgical risk ~1% though higher in adults >30-40 yrs because of degenerative aortic wall changes
• Hypertension persists in 25-50% patients operated on after age 6
• Stent management may be a solution but never technique so less data. Certainly preferred method for patients suffering a recoarctation (repair not always a cure and recoarctation may occur in a new place = need MRI every 5 years)

5. Late outcome
• Long term survival post op lower than general population, but statistics are out of date and it is improving all the time
• Younger patients who have procedures generally have better outcomes
Describe atrial septal defects
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
- Direct communication between the cavities of the atrial chambers that permits blood.
- The true atrial septum is within the rims of the oval fossa; the majority of the remaining tissue seperating the atrial chambers is composed of an infolding of the atrial wall.
- 3 types:
• Secundum = Defects within the oval fossa
• Sinus venosus defects (Superior and inferior) = Deficiency of the infolding of the atrial wall where the SVC and IVS are situated (2-3% ASDs)
• Primum = Commonest form
Part of an atrioventricular septal defect with a common AV junction → no proper rims and affects valves so more complicated to close

2. Genetics
- 2nd most common CHD 10-17%
- 60% found in females
- FH = in one or more close relatives in 2%
- In RBH series, 14% present in adulthood
- Secundum defects associated with Downs syndrome
- When ASD primary diagnosis, 30% are associated with other malformations:
• PV stenosis
• Congen MS or MV prolapse
•VSD (Ventricular septal defect)
• PDA (Patent ductus arteriosus)
• Coarctation

3. Presentation
- Shortness of breath on exertion (SOBOE)
- Palpitations due to atrial arrhythmias (holes in atrium → loss of electrical continuity)
- Recurrent chest infections
- Ejection systolic murmur, best heard in the 3rd intercostal space and produced by increased flow across the pulmonary valve (left to right shunt)
- Cardiac enlargement on CXR
- Occasionally cyanosed if very large defect

4. Management
- If associated with RV dilatation – should be closed as LH flows to RH, increasing pressure on the RV → overloading, dilatation and eventual failure. Use a septal occluder
- However, only need surgical intervention if severe. Otherwise can leave
- Mortality rate < 1%

5. Late Outcome
- Natural history (untreated) = Mortality – infancy 1%, 15% in third decade due to PHT (Pulm HT) and CCF (Congestive cardiac failure) and actual survival rate of 15% at 60 yrs.
- Number of patients with sizeable shunts remain well and symptom free during adulthood = At risk of premature death due to progressive RV dilatation and failure, recurrent pneumonia, PHT, atrial arrhythmias, paradoxical embolus and stroke
Describe ventricular septal defects:
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
- The ventricular septum consists of a muscular septum and smaller membranous septum (just inferior to the aortic valve and divided into two by TV leaflet)
- VSDs arise from failure of growth, alignment or fusion of one or more septal components.
- The left ventricular pressure is greater than the right because of its larger muscle mass, so blood will flow from left to right. Since it will occur through the whole of systole may cause a pansystolic murmur (if small)

2. Genetics
- The commonest CHD malformation
- 20% of all CHD defects
- 1.5 – 3.5 per 1000 live births
- M : F equal
- 5% VSDs associated with chromosomal syndromes including trisomy 13, 18 and 21, so should check the genetics of the parents to find the probability of passing it on

3. Presentation / symptoms in adults
- Children with small VSDs present with murmurs at lower left sternal edge → the smaller the hole the greater the noise (due to squiting into other chamber). Larger holes produce no murmur
- Small defects are relatively benign with potential for spontaneous closure
- Patients with moderate sized VSDs present with SOB and failure to thrive due to excessive pulmonary blood flow (Eisenmenger's syndrome = reversal of shunt from right to left). May also have a palpable parasternal thrill
- Cyanosis does not occur unless Eisenmenger's occurs = deoxygenated blood 'dilutes' oxygenated blood before entering the systemic circulation

4. Management
- Goals:
• To prevent development of irreversible pulmonary vascular disease = very serious
• To preserve left atrial and ventricular function
• To prevent Infective Endocarditis
- Small VSDs – infrequent consultations to document closure = just watch
- Large VSDs – surgical closure
- Mod VSDs – closure may be delayed if signs indicate VSD getting smaller, pressures OK and patient asymptomatic

5. Late outcome
- Course of small VSDs in adult life is not completely benign
- In series of 188 referred to UK centre:
• Spontaneous closure 10% between ages 17-45
• 11% had IE
• Aortic regurgitation developed in 19.7%
- Age related arrhythmias occurred in 8.5%
- 47% no complications
Describe a patent ductus arteriosus:
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
- Blood vessel connecting the prox left pulmonary artery to the descending aorta just distal to the left subclavian artery.
- During fetal life vital structure to bypass the pulmonary circulation by diverting blood flow from right ventricle to descending aorta
- May be deliberately kept patent with prostagladins (and survival is dependent upon patency of the arterial duct) in neonates with pulm atresia or hypoplastic left hearts so that both sides are perfused.
- May result in low overall saturation of blood (but not cyanotic) as desaturated blood ay not be reoxygenated in cases where there is bidirectionality
- Large PDA – rare in adults in the developed world as most repaired in infancy and childhood.

2. Genetics
- Unknown but associated lesions are common

3. Presentation / symptoms in adults
- Small usually silent
- Moderate PDA – present with a loud continuous murmur beneath the left clavicle and bouncy or collapsing pulses or with development of LH dilatation and L-R shunt related PHT
- Eventually become symptomatic with SOB +/or palpitations

4. Management
- Usually surgical or catheter closure = tie off with cotton or plug with coil)

5. Late outcome
- Infective endocaditis may result if the duct never closes
- PHT common in these patients and not reversed with closure

- Small silent – normal life expectancy
- Life expectancy also normal in patients whom have undergone closure; surgical or catheter
Describe aortic stenosis:
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
- LV outflow tract obstruction (LVOTO) may occur
• Below the valve (subvalvular stenosis)
• At the level of the aortic valve (AS)
• In the ascending aorta
- Valvar stenosis is the most common with bicuspid valve accounting for 95%

2. Genetics
- Bicuspid aortic valves reported to occur in 1-2% population
- Congenital valvar AS accounts for approx 5% CHD
- M : F upto 5:1

3. Presentation / symptoms in adults
- Patients with congenital aortic stenosis present with
• Murmur alone +/- Chest pain (not enough blood to the coronary arteries), syncope (not enough blood to the brain) and HF (heart tries to compensate by pumping harder)
- Many patients with bicuspid aortic valve will develop AS and bicuspid Ao Valves account for 50% all AS surgical cases.
- Adults typically develop severe AS by 50-60s as opposed to 70-80yrs for acquired calcific disease

4. Management
- Depends upon
• Age at presentation
• Severity of obstruction
• Presence of symptoms
• Presence of associated other lesions
- Paediatric age group – balloon or surgical valvotomy = balloon preferred as avoids repeating operations when outgrow valves
- Adults – intervention only recommended for symptomatic patients – surgical replacement

5. Late outcome
- For patients diagnosed with valvar aortic stenosis in childhood, annual mortality is upto 2.1% in first three decades then increases to 2.4 – 4.8% thereafter.
- If presentation for first time is in adults, survival without intervention is poor
- 50% survival at 2 years, 20% at 5 yrs
- Mortality from Infective Endocarditis in these patients is 15-30%
Describe the Tetralogy of Fallot:
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it?
- Characterised by:
• Subpulmonary infundibular stenosis
• Large VSD
• Aorta overriding the interventricular septum (right deviation of Aov) → blood flows more into the aorta than pulmonary artery as blood flows across VSD and larger opening (but does depend on the degree of pulmonary stenosis as better perfusion if less stenosis)
• RV hypoertrophy

2. Genetics
- Commonest form cyanotic – 10% CHD
- Slight male predominance
- 15% patients with TOF – deletion of chromosome 22q11
- Found in “Catch 22” (DiGeorge) syndrome – cardiac defect, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia (and chromosome 22)
- Affected subjects have 50% risk of transmitting deletion to offspring

3. Presentation / symptoms in adults
- Cyanosis – due to R – L shunting through VSD and mixing of oxygenated and deoxygenated blood
- The timing of this presentation depends upon the degree of Right Ventricle Onto Tricuspid obstruction
- Vast majority present in infancy
- If RVOTO mild, patients often have minimal cyanosis – so called “pink tetralogy” or “acyanotic fallot”

4. Management
- Palliative or reparative
- Palliative
• Often in the past with Blalock-Taussig shunt (BT shunt)
• Subclavian artery to pulm artery anastomosis = bypass
• Less common, Waterston shunt (Asc Ao – RPA) or Potts shunt (Desc Ao to RPA)
- Modern approach now is that patients undergo a primary repair at presentation
• Many different surgical approaches but all include closure of VSD and relief of RVOT obstruction

5. Late outcome
- Main complications in palliated patients are pulmonary arterial distortion and PHT
- Occurs with any shunt but more common after Potts or Waterston shunt
- With time, biventricular dysfunction ensues and ultimately patients die prematurely from cardiac failure or sudden cardiac death
- Excellent outcome providing VSD closed and RVOTO relieved with no residual Pulmonary regurgitation to allow RV dilatation and failure.
- Survival rates at 32 yrs 86% and 36 yrs 85%
- Older age repair associated with lower survival
- Death is either sudden or due to CCF
- Risk of Sudden Cardiac Death 1.2% 10 yrs to 6% at 25 yrs
Describe the transposition of great vessels:
1. What is it?
2. Genetics
3. Presentation / symptoms in adults
4. Management
5. Late outcome
1. What is it? ]
- Occurs when the trunconal septum develops but does not spiral
- The left artery pumps blood into the pulmonary trunk and the right ventricle pumps blood into the aorta
- Usually also an VSD, ASD or PDA to allow blood to mix or will be born dead

2. Genetics
- Unknown
- 2nd Commonest form of cyanotic CHD
- 5-7% of all CHD
- Incidence 20-30 per 100,000 live births
- M : F 2:1

3. Presentation / symptoms in adults
- Usually presents in the first 24 hours of life as a 'blue baby'
- Severe cyanosis
- May have finger clubbing, and numerous murmurs

4. Management
- Post atrial switch repair
- In the past have used Post Mustard / Senning procedures for transposition of the great arteries

5. Late outcome
- Mean hospital mortality rate post switch repair 4.8%
- Longterm
• 10 yr survival 90%, 20 yr survival 80%
• Much worse if associated VSD – 5 yr 60-70%
- Main longterm problems are sudden cardiac death and complex arrhythmias and RV dysfunction
What is Fontan circulation?
- Operation performed due to a single ventricle
The operation bypasses the right ventricle and by virtue of a surgically corrected atriopulmonary connection and atrial separation, conducts blood into the lungs without the benefit of pulsatile flow → poor flow and thick blood due to gravity, and RH structures are damaged
- Complications:
• Right atriomegaly and hepatic dysfunction
• Systemic venous collaterilization – promote hypoxaemia
• Atrial arrhythmias
• Protein losing enteropathy
→ ascites, pleural and pericardial effusions, peripheral oedema
→ mortality of 4 – 13%
• Thromboembolic events
- Tend not to live past 30 years