Cardiovascular I

Question 1

Heart development at the third week of gestation

Answer 1

1. Heart forms as a pair of endothelial tubes which fuse to become the primitive heart tube.
2. Occurs in the pericardial cavity and is suspended from the dorsal wall by a dorsal mesocardium

Question 2

Sequence of formation I

Answer 2

1. The primitive heart tube develops grooves which divide it into five regions:
   a. Sinus venosus
   b. Atrium
   c. Ventricle
   d. Bulbus cordis
   e. Truncus arteriosus (see diagram).
2. The arterial and venous ends of the tube are surrounded by a layer of visceral pericardium. The tube elongates in the pericardial cavity, with the bulbus cordis and ventricle growing more rapidly than the attachments at either end, so that the heart first takes a U-shape and later an S-shape.
3. Simultaneously heart rotates slightly anticlockwise and twists so that the right ventricle lies anteriorly and the left atrium and ventricle posteriorly.

Question 3

Sequence of formation II

Answer 3

1. The sinus venosus incorporates into the atrium and the bulbus cordis into the ventricle.
2. Endocardial cushions develop between the primitive atrium and ventricle.
3. An interventricular septum develops from the apex up towards the endocardial cushions.
4. Atrium division:
   a. The septum primum grows down to fuse with the endocardial cushions, but leaves a hole in the upper part which is termed the foramen ovale.
   b. A second incomplete membrane develops known as the septum secundum. This is just to the right of the septum primum and foramen ovale. Thus a valve-like structure develops which allows blood to go from the right to the left side of the heart in the fetus (See fetal circulation diagram)
5. At birth, when there is an increased blood flow through the lungs and a rise in the left atrial pressure, the septum primum is pushed across to close the foramen ovale.
6. Usually the septa fuse, obliterating the foramen ovale and leaving a small residual dimple (the fossa ovalis).
7. The sinus venosus joins the atria, becoming the two venae cavae on the right and the four pulmonary veins on the left

Question 4

Aortic arches

Answer 4

1. A common arterial trunk, the truncus arteriosus, continues from the bulbus cordis and gives off six pairs of aortic arches (aortic arch diagram).
2. The first and second aortic arches disappear early
3. Third remains as the carotid artery
4. Fourth becomes the subclavian on the right, and the arch of the aorta on the left, giving off the left subclavian.
5. Fifth artery disappears early
6. Ventral part of the sixth becomes the right and left pulmonary artery, with the connection to the dorsal aortae disappearing on the right but continuing as the ductus arteriosus on the left connecting with the aortic arch.

Question 5

Recurrent laryngeal nerve and aortic arches

Answer 5

1. In the early fetus the larynx is at the level of the sixth aortic arch, and when the vagus gives off its nerve to it this is below the sixth arch.
2. As the neck elongates and the heart migrates caudally, the recurrent nerves become dragged down by the aortic arches.
3. On the right the fifth and sixth are absorbed leaving the nerve to hook round the fourth arch (subclavian) in the adult
4. On the left it remains hooked around the sixth arch (the ligamentum arteriosum) of the adult.

Question 6

Fetal circulation in utero

Answer 6

MUST SEE FETAL CIRCULATION

1. Oxygenated blood from the placenta travels along the umbilical vein, where virtually all of it bypasses the liver in the ductus venosus joining the inferior vena cava (IVC) and then travelling on to the right atrium.
2. Most of the blood then passes straight through the foramen ovale into the left atrium so that oxygenated blood can go into the aorta.
3. The remainder goes into the right ventricle joining the returning systemic venous blood into the pulmonary trunk.
4. In the fetus the unexpanded lungs present a high resistance to pulmonary flow, so that blood in the main pulmonary trunk would tend to pass down the low resistance ductus arteriosus into the aorta.
5. Thus the best-oxygenated blood travels up to the brain, leaving the less well-oxygenated blood to supply the rest of the body.
6. The blood is returned to the placenta via the umbilical arteries, which are branches of the internal iliac artery.

Question 7

Fetal circulation from birth onwards

Answer 7

1. At birth on breathing, there is a rise in the left atrial pressure, causing the septum primum to be pushed against the septum secun- dum and thus to close the foramen ovale.
2. The blood flow through the pulmonary arteries increases and becomes poorly oxygenated, as it is now receiving the systemic venous blood.
3. The pulmonary vascular resistance is also abruptly lowered as the lungs inflate, and the ductus arteriosus becomes obliterated over the next few hours or days.
   a. Closure via prostaglandin-dependent mechanism which causes the muscular component of the ductal wall to contract when exposed to higher levels of oxygen at birth.
   b. Closure of the ductus arteriosus is less likely to occur in very premature babies or those with perinatal asphyxia.
4. Ligation of the umbilical cord causes thrombosis and obliteration of the umbilical arteries, vein and ductus venosus.
5. The thrombosed umbilical vein becomes the ligamentum teres in the free edge of the falciform ligament.

Question 8

Congenital Heart defects: Malposition

Answer 8

1. Dextrocardia, which is a mirror image of the normal anatomy
2. Situs inversus, where there is inversion of all the viscera. (Appendicitis may present as left iliac fossa pain in this condition.)
3. In pure dextrocardia there is no intracardiac shunting and cardiac function is normal.

Question 9

Congenital Heart defects: Left to right shunts

Answer 9

Left to right shunts (late cyanosis)

1. Atrial septal defect (ASD) This may be from the ostium primum, secundum or sinus venosus and represents failure in the primary or secondary septa.
2. Clinically important septal defects with intracardiac shunting should be differentiated from a persistent patent foramen ovale, where a probe may be passed obliquely through the septum, but flow of blood does not occur after birth, because of the higher pressure in the left atrium.
3. This condition is said to occur in 10% of subjects, but it is not normally of any significance. Atrial septal defects requiring closure have previously been treated with a pericardial patch but more recently catheter-introduced atrial baffles made of Dacron have been used.

Question 10

Congenital heart defects: VSD

Answer 10

Ventricular septal defect (VSD) is the most common abnormality. Small defects in the muscular part of the septum may close. Larger ones in the membranous part just below the aortic valves do not close spontaneously and may require repair.

Question 11

Congenital heart defects: PDA

Answer 11

Occasionally this normal channel in the fetus fails to close after birth and should be corrected surgically because it causes increased load to the left ventricle and pulmonary hypertension, and along with septal defects may later cause reverse flow and, therefore, late cyanosis.

Question 12

Congenital heart defects: Eisenmenger’s syndrome

Answer 12

Pulmonary hypertension may cause reversed flow (right to left shunting). This is due to an increased pulmonary flow resulting from either an ASD, or VSD or PDA. When cyanosis occurs from this mechanism it is known as Eisenmenger’s syndrome.

Question 13

Congenital heart defects: Right to left shunts (cyanotic)

Answer 13

Fallot’s tetralogy

1. The four features of this abnormality are
   a. VSD
   b. A stenosed pulmonary outflow tract
   c. A wide aorta which overrides both the right and left ventricles
   d. Right ventricular hypertrophy.
2. Since there is a right to left shunt across the VSD there is usually cyanosis at an early stage, depending mainly on the severity of the pulmonary outflow obstruction.

Question 14

Congenital heart defects: Obstructive non-cyanotic abnormalities

Answer 14

Coarctation of the aorta

1. This is a narrowing of the aorta which is normally just distal to the ductus arteriosus due to the obliterative process of the ductus.
2. There is hypertension in the upper part of the body, with weak delayed femoral pulses.
3. Extensive collaterals develop to try and bring the blood down to the lower part of the body, resulting in large vessels around the scapula, anastomosing with the intercostal arteries and the internal mammary and inferior epigastric arteries.
4. These enlarged intercostals usually cause notching of the inferior border of the ribs, which is a diagnostic feature seen on chest x-ray.
5. This is another condition which used to require a major thoracic operation but now can frequently be treated by balloon angioplasty.

Question 15

Congenital heart defects: Valve abnormalities

Answer 15

Abnormalities of the valves Any of these may be imperfectly formed and tend to cause either stenosis or complete occlusion (atresia). The pulmonary and the aortic valves are more frequently affected than the other two.

Question 16

Phases of the cardiac cycle

Answer 16

Each cycle can be broken down into two phases each for diastole and systole:
Systole:
Contraction (I) – mitral and tricuspid valve 
closure
Ejection (IIa & b) – aortic and pulmonary valve 
opening.

Diastole:
Relaxation (III) – aortic and pulmonary valve closed
Filling (IVa, b & c) – mitral and tricuspid valve open. 


See cardiac cycle diagram. It is convenient to start when the ventricles are still in diastole at the beginning of atrial systole.

Question 17

Phase IVc, atrial systole

Answer 17

1) 
The SA node depolarises and atrial musculature contracts (P wave on ECG).
2) Atrial pressure rises and blood flows down the pressure gradient through the AV valves to the ventricles, completing the last 15% of ventricular filling. This is the end of diastole

Question 18

Phases I & II, ventricular systole

Answer 18

1) The electrical impulse from the atria now reaches the ventricles, which contract (QRS on ECG) – phase I.
2) The pressure in the ventricles rises, closing the AV valves but not yet opening the semilunar (aortic and pulmonary valves). Thus all four valves are closed and the volume of blood in the heart remains constant as the pressure rapidly increases (isovolumetric contraction).
3) When the pressure in the ventricle exceeds that in the aortic (or pulmonary) artery the semilunar valves open. The pressure in the aorta and ventricle (and pulmonary artery and ventricle) is now the same, and both continue to rise rapidly.
4) The opening of the valves marks the start of the ejection phase or phase II. A maximum pressure of 120mmHg is reached on the systemic side and 18mmHg on the pulmonary.

Question 19

Phase III, diastolic relaxation

Answer 19

1) Having reached maximum pressure the ventricles now relax but maintain their volume for a short while (isovolumetric relaxation).
2) The pressure inside drops below that of the aorta (and pulmonary artery) so the semilunar valves close. All four valves are closed again.
3) The end of phase III is marked by the start of a fall in ventricular volume as the ventricles relax further. The ventricle ejects about 60% of its volume, the ejection fraction, which is defined as follows:
Ejection fraction = SV/LVEDV

SV is stroke volume; LVEDV is left ventricular end diastolic volume.

Question 20

Phase IV, diastolic filling

Answer 20

1) The filling phase of diastole can now occur. It is important to realize that the downward displacement of the valves during ejection ensures a low atrial pressure (suction effect) and hence rapid initial filling (phase IVa).
2) This rapid rate of filling declines as atrial volume increases (IVb).
3) Finally active atrial contraction begins again (phase IVc).
4) The ventricles are ‘topped up’ by about 15% at rest but much more at higher heart rates. Hence a failure of atrial contraction, espe- cially at higher heart rates (e.g. fast atrial fibrillation, exercise) becomes more important and possibly life threatening.

Question 21

Heart

Answer 21

1) The first heart sound is caused by closure of the mitral (and much quieter tricuspid) valve. It is best heard at the apex.
2) The second heart sound is produced when the aortic and pulmonary valves close and is best heard at the base of the heart.
3) A third heart sound may occur in early diastole if there is an abrupt end to ventricular filling. This occurs in an hyperdynamic circulation, such as pregnancy or anaemia.
4) A fourth heart sound may occur in late diastole and indicates a stiff (diseased) ventricle. It is only heard if the atria contract to augment filling and generally indicates heart failure or ventricular failure

Question 22

JVP

Answer 22

There are five waveforms that make up the jugular venous pulse and its relative the central venous pressure trace. They represent right atrial activity. Three are positive and and two negative. They can be clearly identified by physicians on inspection of the internal jugular vein

1) a wave: Atrial systole. Not seen in AF. Increased in tricuspid or pulmonary stenosis. Heart block causes variable a-waves and even `cannon ́ waves
2) c wave: Leaflets of the tricuspid valve bulge into right atrium during isovolumetric contraction
3) v wave: Right atrium is rapidly filled while tricuspid valve is closed
4) 
x descent: Atrium relaxes and tricuspid valve moves down
5) y descent: Tricuspid valve opens, blood flows from right atrium to right ventricle

Question 23

Cardiac cell types

Answer 23

Cardiac tissue has two types of cell:
• Cells that initiate and conduct impulses
• Cells that conduct and contract.

Question 24

Generation of the cardiac impulse

Answer 24

The SA node and conducting system do not have a resting membrane potential. The cells are constantly depolarising at a slow rate after each repolarisation. This slow depolarisation continues until the threshold potential is reached and an action potential is triggered (see diagram).

1) The maximum transmembrane potential of the SA node is about -50 mV.
2) The cell membrane is relatively permeable to sodium, so this ion gradually ‘leaks in’, lowering the transmembrane potential.
3) When -50 mV is reached a sudden depolarisation occurs, and this is conducted to other cells, initiating a cardiac cycle. Depolarisation is a sudden short-lived increase in permeability to sodium. The SA node has the fastest rate of depolarisation (i.e. the greatest permeability to sodium).
4) Depolarisation/permeability is increased by sympathetic activity and decreased by vagal (parasympathetic) activity. If the rate of spontaneous depolarisation of the SA node is slowed sufficiently, then the cardiac impulse will be generated from elsewhere in the conduction system (the second fastest pacemaker is the AV node).

Question 25

Repolarisation

Answer 25

1) Potassium now diffuses out of the cell down the electronic gradient, rapidly restoring the ‘resting membrane potential’
(-80 mV).
2) Before this can occur, the inward movement of calcium ions slows this process down and produces a plateau phase of about 200ms (see cardiac action potential).
3) During this period cardiac muscle cannot be stimulated further (it is inexcitable)
4) This plateau phase is unique to cardiac muscle; without it, rhythmic contraction would be impossible.

Question 26

Effect on heart: Hypocalcaemia

Answer 26

Decreased contractility

Decreased calcium available from the sarcoplasmic reticulum


Question 27

Effect on heart: Hypercalcaemia

Answer 27

Initially increased contractility

Increased calcium available from the sarcoplasmic reticulum

Question 28

Effect on heart: Hypokalaemia

Answer 28

Initially positive chronotropic and inotropic effects


 Decreased repolarisation of the myocardium
so more calcium may enter the cells

Question 29

Effect on heart: Hyperkalaemia

Answer 29

Decreased rate of conduction and slowing of the heart, dysrhythmias, reduced force of contraction (tall-peaked T waves on ECG). Eventual cardiac arrest
Inactivation of the sodium channels. Accelerated repolarisation of the myocardium, so that less calcium can enter the cells

Question 30

Effect on heart: Low pH

Answer 30

Decreased contractility

Multiple factors

Question 31

Cardiac output

Answer 31

CO= SV x HR

Question 32

What affects the stroke volume

Answer 32

1) Preload = ventricular end diastolic volume i.e. amount of stretch of the ventricle (the
‘wall stress’ of the myocardium);
2) Afterload = total peripheral resistance (TPR)
3) Contractility = capacity of myocardium to 
‘respond to’ preload and afterload.
Sympathetic stimulation increases myocardial contractility and heart rate both by direct neuronal stimulation and by circulating catecholamines.
Heart rate is increased not only by increasing sympathetic stimulation but also by decreased vagal stimulation.

Question 33

Kortokoff sounds

Answer 33

There are five phases:
phase 1: Appearance of a tapping sound heard at systolic pressure;
phase 2: Sounds become muffled or disappear;
phase 3: Sounds reappear;
phase 4: Sounds become muffled again. In the UK 
this is taken as diastolic pressure; and
phase 5: Sounds disappear. (in 
most automated blood pressure monitors this is taken as the diastolic pressure.

Question 34

Where does resistance occur in the circulation?

Answer 34

1) 
The arterioles and capillaries each account for about 25% of TPR.
2) These are often referred to as resistance vessels.
The arterioles contain smooth muscle and hence can exert considerable control over resistance and flow through the capillaries. Further they control the number of capillaries which are open to flow at any one time.

Question 35

Blood pressure control: Neural activity

Answer 35

1) The adrenergic fibres of the sympathetic nervous system are the predominant pathways whereby the systemic circulation is controlled.
2) Vasomotor areas in the medulla have descending pathways to the thoracolumbar areas of the spinal cord.
3) Postganglionic fibres then go from ganglia of the sympathetic chain to the vascular smooth muscle.
4) The major transmitter which acts on receptors to cause vasoconstriction is noradrenaline.
5) The vasomotor centre discharges in response to afferent stimuli from baroreceptors, chemoreceptors and from the cortex itself e.g. anticipation of exercise.
6) Discharge from the vasomotor centre and increased adrenergic activity is a redistribution of blood from skin, muscle and gut to heart, brain and kidney areas, where there are fewer adrenergic receptors or thinner smooth musculature.
7) By contrast the cholinergic fibres of the sympathetic nervous system cause vasodilatation in skeletal muscle. Stimulation of these fibres results in a redistribution of blood from skin and viscera to skeletal muscle.

Question 36

Spinal shock

Answer 36

1) Transection of the spinal cord above the thoracolumbar region will result in a loss of not only sensory and motor functions but also in loss of sympathetic vasomotor tone, contributing to the condition known as spinal shock.
2) Very high transections of the cord not only allow profound falls in blood pressure but also result in the absence of sympathetic innervation of the myocardium, which can result in unopposed vagal stimulation and profound bradycardia (especially during endotracheal intubation, or the passage of a nasogastric tube to control an associated ileus).

Question 37

Blood pressure control: Hormones

Answer 37

1) Adrenaline and noradrenaline from sympathetic nerve endings and the adrenal medulla pour into the circulation during stress (not day to day regulation)
2) Angiotensin II is a powerful vasopressor produced by the action of renin on angiotensinogen. Renin is released when there is a decrease in the perfusion of the kidney. Whilst the vasoconstriction produced is great, it is more likely that this hormone acts mainly by increasing aldosterone concentrations, which in turn promote salt and water retention.

Question 38

Blood pressure control: Local control

Answer 38

The term autoregulation is used to refer to the mechanism by which blood flow is maintained at a constant rate over a wide range of perfusion pressures. This is most pronounced in the renal and cerebral circulation. There are two basic mechanisms:
1) A fall in blood pressure results in a reduction in blood flow. Local metabolites accumulate and these cause local vasodilatation, ultimately mediated by nitric oxide.
2) Myogenic response – this involves local neural reflex in response to stretch. It occurs at the level of the first-order arteriole.
3) The final common pathway for the relaxation of smooth muscle is via nitric oxide.
mean arterial pressure = CO x TPR

Question 39

Baroreceptors

Answer 39

Baroreceptors are found in the wall of the aorta and carotid sinus. They are stretch receptors which, when stimulated (by increased blood pressure), lead to a reflex reduction in vasoconstriction, venoconstrictor tone, and to a lower heart rate. This leads to a fall in TPR, cardiac output and blood pressure.
As blood pressure falls the baroreceptors become less stretched: vasoconstriction, venoconstriction and heart rate increase, and the fall in blood pressure is reversed.
In addition to the baroreceptors, there are other receptors to be found in the carotid and aortic bodies. These are chemoreceptors that respond to hypoxaemia and also to hypoperfusion. Stimulation results in an increase in sympathetic discharge and an increase in blood pressure.

Question 40

Dopamine

Answer 40

1) Stimulation of dopamine receptors results in an increase in renal blood flow, glomerular filtration rate (GFR) and sodium excretion.
2) As the dose increases, β1 receptors are also stimulated, resulting in an increased heart rate and contractility.
3) Even higher doses stimulates α1 receptors, which may result in decreased tissue perfusion (and GFR) despite a higher blood pressure. About 50% of the action of dopamine is mediated by the release of noradrenaline from nerve terminals.

Question 41

Dobutamine

Answer 41

1) This is a β1 (and to a lesser extent β2) agonist and a synthetic derivative of isoprenaline.
2) Causes an increased heart rate, contractility, cardiac output and coronary blood flow combined with afterload reduction.
3) At higher doses the tachycardia may well result in a disadvantageous effect on the myocardial oxygen supply/demand ratio and limit therapy.
4) Its main advantage over isoprenaline is that it causes less tachycardia and it does not cause the release of noradrenaline.

Question 42

Adrenaline

Answer 42

1) Has both α and β effects.
2) It is used mainly as a bronchodilator and in the treatment of acute anaphylactic reactions. It has a great potential for causing arrhythmias and so must be infused with caution. This propensity to cause arrhythmias is put to use in cardiac arrest situations where it can be used to provoke ventricular fibrillation, which may then respond to DC shock.
3) It is most effective on α1 receptors, which are vasodilatory and found mainly in skeletal muscle and causes increasing cardiac output and TPR as dose increases.
4) Vasoconstriction is most pronounced in the skin and kidneys and can lead to acute renal failure. The combination of vasodilatation in the muscle beds and vasoconstriction elsewhere leads to a characteristic widening of the pulse pressure (systolic blood pressure increased more than diastolic).
5) Due to its effect on renal blood flow the role of adrenaline in circulatory support is reserved for refractory hypotension with a low peripheral vascular resistance.

Question 43

Noradrenaline

Answer 43

1) This is a powerful α1 stimulant (although it does increase myocardial contractility).
2) Infusions result in vasoconstriction and an increase in TPR with increased systolic and diastolic blood pressure.
3) Renal blood flow declines with increasing infusion rates. Cardiac output is unchanged or decreased, but an increased workload results in a higher oxygen demand.
4) Its use is largely restricted to the treatment of shock where there is a very low peripheral vascular resistance (e.g. sepsis).

Question 44

Isoprenaline

Answer 44

1) This is exclusively a β stimulant affecting receptors of the heart, bronchi, skeletal muscle and gut vasculature.
2) Infusion of isoprenaline reduces TPR by vasodilatation in skeletal muscle, kidney and mesentery.
3) It has positive inotropic and chronotropic actions and produces an increased cardiac output. Tachycardia limits the clinical use of isoprenaline.

Question 45

Nitrates

Answer 45

1) These can be used where vasodilatation may be required: e.g. pulmonary oedema or left heart failure.
2) The principle is to reduce TPR and to venodilate, reducing afterload and preload respectively. Nitrates are predominantly venodilators.
3) Where arterial vasodilatation is required (reduced afterload) hydralazine may be used.
4) Close supervision and monitoring of the circula- tion, e.g. with arterial lines, CVP, PCWP and cardiac output measurement, are often required.

Question 46

Phosphodiesterase inhibitors

Answer 46

1) These work by decreasing the rate of breakdown of cAMP by phosphodiesterase III (conversely β stimu- lation increases production of cAMP).
2) The effect is to increase myocardial contractility. Amrinone is a potent inotrope with marked vasodilator effects that reduce SVR and PVR with reductions in afterload to the left and right heart.
It has little chronotropic effect, but may cause significant hypotension