Physiology: Cardiovascular Physiology

cardiovascular physiology

Comparison of skeletal and cardiac muscle
Muscle cells (skeletal muscle)
-          The cells are called skeletal muscle fibres. They run the whole length of the muscle.
-          They have hundreds of nuclei, and are formed by the fusion of hundreds of myoblasts – each nucleus represents the contribution of one myoblast.
-          Myoblasts that don’t contribute to the fibre are found inbetween the fibres, and are called satellite cells – these are a form of stem cell that in the event of cell damage will join to a nearby fibre to help repair.
-          The cell membrane is called the sarcolemma, and the cytoplasm is called the sarcoplasm.
-          The cells have t-tubules running through them that contain extracellular fluid – thus providing a large surface area in connection with the outside environment. The t of t-tubule stands for transduction. The t-tubules loop around each ‘myofibril’ of the muscle fibre. Myofibrils are the contractile unit, and contain the myofilaments.
-          On either side of each t-tubule there is another tube – part of the sarcoplasmic reticulum called the terminal cysternae. This basically contains a giant reserve of calcium ions to be released for contraction.
-          There are also lots of mitochondria and glycogen granules found in muscle fibres.
-          Troponin is a molecule found on thin filaments. It will bind to calcium, and when it does so, this causes a change in shape of the troponin-tropomyosin complex, exposing its binding site, and allowing it to bind to the myosin head of the thick filament.
-          ACh causes muscle contraction – this is released by exocytosis, will bind to receptors on the skeletal muscle cell surface, and will cause the opening of Na+ channels, causing an influx of Na+ into the cell, which in turn will cause a release of Ca2+ by the terminal cysternae.
-          The cell will repolarise because K+ will be forced out by the positive charged caused by the influx of Na+. The balance of Na+ and K+ will be restored by the action of the Na+/K+ pump.
Cardiac Muscle cells
-          Are much smaller than skeletal muscle cells. They generally have one nucleus although they can have up to 5.
-          There are no triads – i.e. there are no terminal cysternae surrounding the t-tubules. However, the mechanism of contraction (from Ca2+ release from the sarcoplasmic reticulum, onwards) is exactly the same.
o   However – unlike in skeletal muscle – Ca2+ is also allowed to enter the cell from the ECF.
o   Also – unlike skeletal muscle – it is pacemaker cells that provide the initial action potential – not an ACh stimulus from a nerve ending.
-          There are massive reserves of glycogen and lipids, as well as loads of mitochondria (up to 25% of the cell volume) to provide the energy needed. Pretty much all the metabolism in cardiac cells in aerobic. Most of the energy comes from direct utilisation of lipids and carbohydrates, and not the breakdown of glycogen.
-          The cells do not run the whole length of the heart. Instead, many cells are connected by intercalated discs – which hold cells together by means of desmosomes. There are also gap junctions between adjacent cells, allowing the limited exchange of molecules. The main function of the gap junctions is to create a direct electrical connection between cells. this means an action potential can easily cross the intercalated disc. This basically means that the heart cells contract as if they were one giant cell – this is called functional syncytium.
-          Cardiac muscle does not contain satellite cells – and thus repair is not easily achieved. Scarring is the only form of repair mechanism.
The Conducting system
-          The ability of the heart to contract on its own without external nervous input is known as autorhytmnicity or automaticity.
-          This rhythm is generated by the sinoatrial node(SA node). This is found in the wall of the right atrium. With no nervous or hormonal stimulation, it will generate a heart rate of 60-100bpm.
o   The cells of the SA node have a negative intracellular potential. But they have ‘leaky’ sodium channels that constantly allow a small number of sodium ions into the cell. Once the inside of the cell reaches a threshold voltage (of about -45mV) then voltage controlled sodium/calcium channels open and allow loads of positive ions into the cell, thus generating the action potential. These will close and potassium channels will open once the cell reaches a certain positive potential. The potassium channels allow potassium out of the cell, thus repolarising (hyperpolarising it back to about -60mV – thus to allow the ‘leaky’ channels to have an effect) it. The balance of sodium and potassium within the cell is controlled by the sodium/potassium pump.
-          The atrioventricular node – which is found at the junction of the atria and ventricles is also able to generate action potentials if the SA node is not doing so. It can generate a heart rate of 40-60 bpm.
-          The purkinje fibres are able to also generate their own rhythm – at about 20-40bpm – if they receive no other signal to depolarise before this time.
o   The term rhythm is used to refer to which part of the heart is controlling the heart rate. When the heart is functioning normally, and the SA node is controlling the rhythm we call it the sinus rhythm.
-          Ventricular muscles fibres depolarise in a different manner to SA node fibres. They have ‘fast’ sodium channels that allow the cell to depolarise very quickly. The resting potential of the cell is also more negative than that of the SA node – and these fast channels can only become active at such negative potentials. There are no leaky channels in ventricular fibres – they are depolarised when the receive an action potential from an adjacent cell.
-          There is a fibrous skeleton that separates the atrium from the ventricle – and thus the action potential cannot travel from on to another. Instead, the signal HAS to pass via the AV node along special inter-nodal pathways.
o   This mechanism controls the time delay between the atria and the ventricles contracting. There needs to be a delay to allow for filling of the ventricles. Normally, this delay is about 0.16 seconds. The delay is caused by a reduced number of gap junctions between cells in the pathway, and thus the signal cannot travel as quickly.
o   One way conduction also occurs at the AV bundle – and thus the signal cannot potentiate back to the atria causing them to contract again. In some cases this mechanism can be damaged, and can lead to arrhythmias.
-          The signal travels from the SA node, through atrial fibres, until it reaches the AV node. From here the signal travels down the bundle of His and then splits into the two bundle branches (the left and right bundle branches), until it eventually goes into the purkinje fibres.
-          The purkinje fibres have a huge number of gap junctions, and transmit the signal extremely quickly (150x as fast as AV node fibres do!). This means that the signal is spread almost instantaneously around the ventricles, so that the whole ventricle can contract at the same time. However, the signal travels even more quickly through the Bundle of His and bundle branches that it does through the purkinje fibres!
-          Parasympathetic nervous fibres – from the vagus nerve supply all of the heart, but most extensively they supply the SA and AV nodes. They release ACh which will:
o   Decrease the rate and rhythm of the sinus node
o   Decrease the excitability of the AV junctional fibres – these are the fibres found between the SA nodes and the AV node
o   So the overall effect is to REDUCE the excitability of the heart.
-          The ACh will open potassium channels in the muscles fibres, and thus cause excess hyperpolarisation – thus is takes longer for the threshold voltage to be reached by the ‘leaking’ of the leaky sodium channels.
-          ACh is very rapidly removed by acetylcholinesterase, and so its effect is very shortlived. ACh stimulation can be so strong as to stop the SA and AV nodes producing action potentials completely. This will allow the purkinje fibres to act as an ectopic pacemaker – a mechanism known as the ventricular escape.
-          Sympathetic nervous fibres – these are also distributed to all areas of the heart, but there is particularly strong representation in the ventricles. The number of sympathetic nerves far outnumbers the number of parasympathetic nerves. These fibres release noradrenaline and it is thought that this increases the permeability of the cells to sodium and calcium ions. This mechanism can not only increase the heart rate, but also increase the contractile strength of the heart (due to extra calcium ions; and calcium ions role in contraction).
-          There are cardiac centres in the medulla that control the amount of parasympathetic and sympathetic stimulation. These centres receive input from areas of the hypothalamus involved with cardiac regulation.
-          Normally, there is a moderate amount of sympathetic stimulation, which keeps the heart rate about 30% above its own automatic base rate.
-          Adrenaline and noradrenaline increase the heart rate and contractile strength by acting on β-receptors – thus β-blockers will reduce the heart rate and contractile strength by blocking sympathetic activity of the heart.
-          Heat can also affect heart rate – the higher the temperature, generally the higher the heart rate – this is presumable because heat increases the permeability of the cardiac cells to ions, and thus in cold weather, the self-excitatory process occurs more slowly.
o   Heat will also increase contractile strength, but only for a short amount of time – after prolonged heat the heart muscles will get ‘tired’ and thus the contractile strength will decrease.
The cardiac cycle
-          Systole – the period of contraction
-          Diastole – the period of relaxation where the chambers fill.
o   Note that 70-80% of ventricular filling is passive – it is only the last 20-30% that is forced in by the atria.
-          Atrial systole only lasts about 0.1 seconds. As soon as the atria enter diastole, then the ventricles begin systole. The amount of blood in the ventricles just before systole begins is known as the end-diastolic volume (EDV).
-          Ventricular systole – as this occurs, there is a short period whereby the ventricles will contract, but the semilunar valves will not open – this is called isometric contraction. Once enough pressure has built up, the semilunar valves will open. The first 70% of blood will leave the ventricles very quickly (fast ejection) and the other 30% will leave the ventricles more slowly (slow ejection).
-          Stroke volume – this is the volume of blood pumped from one ventricle with each contraction. You calculate it by subtracting the end systolic volume (ESV) from the end diastolic volume (EDV). The normal stroke volume is about 60% of the EDV. This percentage is known as the ejection fraction.
o   Normal EDV – 120ml
o   Normal ESV – 40-50ml
o   Normal SV – 60-70ml
§    The EDV can be increased to about 180ml, and the ESV reduced to about 10ml in a normal heart to increase the supply. This will virtually double the amount of blood flow (i.e. during strenuous exercise).
Cardiac output is the amount of blood pumped by the heart in one minute.
Cardiac output (ml/min) = Heart rate (beats/min) x Stroke volume (ml/beat)
You can increase both the HR and the SV to increase the cardiac output. HR can increase by 2.5x, and SR by 2x. Thus the cardiac output can increase by 5x.
The Frank/Starling Law states that the more the heart muscle is stretched during filling, the greater the strength of the contraction – i.e. more blood in = more blood out, i.e. bigger EDV = bigger SV.
This conclusion comes from the analysis of Preload and Afterload. The preload is the amount of tension in the ventricular muscle at the begging of the contrition (i.e. how much the heart muscle has been stretched), and the afterload, is the amount of pressure needed to force open the semilunar valve.
The greater the EDV, the greater the preload, and the greater the SV. However, this is only true up to a certain point, because once the ventricular fibres become overstretched, they will not contract as effectively (however this limit is large, and in a normal heart it will not normally be reached).
The greater the afterload the greater the amount of pressure needed to open the semilunar valve, and thus the isovolumetric contraction time is increased, and the SV is decreased. The afterload can be increased by anything that restricts blood flow, e.g. arterial disease, constriction of blood vessels, circulatory blockage etc etc.
Stretching of the atria as a result of rapid filling of the atria due to increased venous return, will cause a more rapid depolarisation and thus increase heart rate – this is known as the Bainbridge reflex (or the atrial reflex).
Heart Valves
-          Bicuspid (Mitral) valve – separates left atrium/ventricle
-          Tricuspid valve – separates right atrium/ventricle
-          Semilunar valve – pulmonary (right), aortic (left).
The valves all open and close passively. The papillary muscles are connected to the tri/bicuspid valves by the chordinae tendineae. These muscles contract with the ventricles, and prevent the tri/bicuspid valves from bulging/opening backwards into the atria when the ventricles contract.
The semilunar valves are much smaller in diameter than the tri/bicuspid valves, and thus blood flows at a much higher rate through these valves.
Aortic pressure – entry of blood into the arteries causes the arterial smooth muscle to stretch. At the end of ventricular systole, there is elastic recoil of the arteries, causing a small backflow of blood towards the ventricles and increasing ventricular pressure very slightly before the aortic valve has time to close. This will produce the dicrotic notch on a graph of ventricular pressure.
Heart sounds
-          S1 – caused by closing of the AV valves
-          S2 caused by closing of the semilunar valves
-          S3 caused by filling of the ventricles
-          S4 caused by contraction of the atria
Notes by Tom Leach

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