INTRODUCTION TO THE CARDIOVASCULAR SYSTEM


Describe the functions of the cardiovascular system and its component parts: heart, arteries, arterioles, capillaries and veins

The goal is to supply all the cells of the body with oxygen and nutrients and get rid of waste: so it needs to move a fluid around the body. To move a fluid, there needs to be a pressure difference, because the way that fluid moves is from a region of high pressure to a region of lower pressure.

What provides this pressure difference? The heart. So this is its function.

The vessels of the body can be divided into two main groups: veins and arteries. Arteries come out of the heart and veins go into the heart. In general, veins carry deoxygenated blood and arteries oxygenated blood (the opposite is true of the veins and arteries of the lungs).

There are four types of arteries:

  1. Elastic arteries

  • They can accommodate the stroke volume and smooth the flow due to their abundance of elastin and collagen – such vessels are the aorta, iliac arteries and pulmonary trunk: temporary storage vessels that expand about 10% during each heartbeat.

  • ARTERIOSCLEROSIS – occurs when elastin starts breaking down with age and collagen increasingly dominates the properties of elastic vessels.

  1. Conduit and feed arteries

  • These arteries deliver blood to the organs.

  • Their tunica media contains a lot of smooth muscle and is thicker relative to the lumen compared to elastic arteries.

  • They are rich in sympathetic innervation and can change their diameter actively.

  • Dilatation: local increase in blood flow to skeletal muscle during exercise.

  • Contraction: reduces peripheral blood flow.

  • Vasospasm: intense and sustatined contraction of conduit arteries, lifesaving in severing of limbs for example. However vasospasm evoked by cerebral haemorrhage can cause a stroke, and of diseased coronary arteries can cause cardiac angina at rest (variant angina)

  1. Resistance vessels: terminal arteries and arterioles

  • Pressure falls sharply across these vessels because they are very narrow, so they dominate the resistance of the entire circulation

  • Proof of this dominance is provided by the fact that there is basically no BP drop in the elastic arteries and conduit arteries (which have very large lumen and little resistance) and there is a large BP drop here

  • There are proximal resistance vessels (terminal arteries) which are richly innervated by sympathetic vasoconstriction nerve fibres and have thick muscular walls

  • Distal resistance vessels (terminal arterioles) are poorly innervated, with one to three layers of smooth muscle cells

  • These resistance vessels are therefore the ‘taps’ regulating local blood flow and capillary perfusion through vasodilatation and restriction

  1. Exchange vessels

  • These are capillaries, and responsible for the actual exchange of materials between the blood and cells of the body

Describe the involvement of the different chambers of the heart in the pumping of blood.

Explain how cardiac depolarisation in generated in the SA node and distributed to the cardiac chambers by the cardiac conduction system

Briefly describe cardiac excitation contraction coupling

Why do we say Ca2+ is the most important thing when it comes to heart contraction? At first this would confuse me because isn’t it the same with skeletal and smooth muscle too? There is no contraction without Ca2+ there either. However, there is a difference when it comes to cardiac muscle.

We know that the heart can pump with different strengths: this is where the differences in volume and pressure come from. In skeletal muscle, there is recruitment: if we want a little contraction, for lifting something light for example, we only contract some myocytes, and if we want to lift something heavier, we recruit more. It depends on how many groups of muscle cells we have activated and contracted, because every twitch of an individual skeletal muscle fibre occurs at full power.

Heart muscle cells however are connected to one another through gap junctions. It is therefore impossible to isolate contraction (if we could it would be devastating anyway – what happens when we have an MI and part of the heart doesn’t contract, or in ventricular fibrillation when cardiac myocytes do not contract in synchrony). So how are different strengths of contraction achieved with cardiac myocytes?

Unlike skeletal muscle, in cardiac myocytes the amount of contraction is proportional to the amount of Ca2+ available. With little Ca2+ we have less contraction, and with more Ca2+ we have more contraction. Typically, the contraction of heart muscle cells in around 40% of the maximum possible.

CONTRACTILE FORCE IS PROPORTIONAL TO CROSSBRIDGE ACTIVATION IN CARDIAC MYOCYTES

There are two different parts of sarcoplasmic reticulum in the cardiac myocyte:

  • Junctional SR – located near the T-tubules – mainly releases Ca2+

  • Network SR – located near the interior of the cell – mainly pumps Ca2+ into the SR

As Ca2+ enters through L-type Ca2+ channels (stay open for a long time/close slowly), the concentration of Ca2+ is quickly raised in the subsarcolemmal space = trigger Ca2+. This activates a cluster of release channels RyR receptors – since the entry of Ca2+ happens all around the cell, there is a synchronous release of Ca2+ from the sarcolemmal store. This also means that the amount of Ca2+ released is proportional to the size of the iCa, one cluster is observed not to activate others around it.

Where does the Ca2+ go after contraction? 75-90% is pumped back into the SR interior by Ca2+ ATPase pumps, and then the remaining 10-25% are expelled by the sarcolemmal 3Na+/Ca+ exchanger.

Phospholamban is an inhibitory protein of the SR Ca2+ ATPase pumps, it is inhibited by adrenaline and noradrenaline which is why they increase the rate of myocardial relaxation = lusitropic action. This also increases the SR Ca2+ content and hence the amount of Ca2+ released to activate contraction – this increases the force of contraction.

How do Ca2+ levels not infinitely rise in the SR then? There is a simple negative feedback loop by which high Ca2+ concentration in the cytoplasm increases the probability that the 2Na2+/Ca2+ exchanger favours Na2+ entry rather than Ca2+ expelling until the levels are normalised again.

Summary of cardiac contraction

  1. Resting potential is about -80mV (highly permeable to K+, small back-leak of Na+)

  2. Action potential opens Voltage-dependent Na+ channels: iNawhich depolarize the myocyte: ACTION POTENTIAL SPIKE – spike because a fast raise, but also fast inactivation

  3. Early partial repolarisation: Na+ channels close

  4. Second inward current: extracellular Ca2+ ions iCamaintains the prolonged depolarisation: PLATEAU 200-400ms: ABSOLUTE REFRACTORY PERIOD

  5. Repolarisation begins: outward K+ currents iKVand iKirterminate the plateau.

  • TACHYCARDIA and HYPOXIA: the plateau is shortened due to increased K+ currents

  • CHRONIC HEART DISEASE: reduced K+ currents lengthen the plateau

  1. Trigger Ca2+ pass through L-type Ca2+ channels into the subsarcolemmal space activating RyR channels in the junctional SR: CALCIUM INDUCED CALCIUM RELEASE – about half the Ca2+ stores are release increasing Ca2+ concentration to about 1uM

  2. Ca2+ binds to troponin-tropomyosin complex on actin, exposing myosin binding sites for myosin to form crossbridges, the recocking of myosin needs ATP so the myocytes are rich in mitochondria and need a rich O2 supply

Summary of factors that affect cardiac contractile force

  1. Stretch of sarcomeres in diastole: increase the sensitivity of the contractile machinery to Ca2+, which leads to more cross-bridge activation and contractile force (the length-tension relationship)

  2. Size of the systolic Ca2+ transient determines the number of cross-bridges activated at a given length:

  • ADRENALINE and NORADRENALINE increase the iCaincreasing the store size and supplies more trigger Ca2+

ISCHAEMIA AND Ca2+

The sarcoplasmic reticulum Ca2+ stores can become overloaded, especially with B-adrenoceptor stimulation by catecholamines is high. This can cause spontaneous partial discharge of the overloaded store during diastole: this causes depolarisation, due to the increased 3Na+/1Ca2+ exchanger current. This can trigger premature action potentials and arrhythmia.

Draw a diagram of the changes in aterial blood pressure during the cardiac cycle, and explain the role of the Windkessel effect in maintaining flow during diastole

Blood is pumped in a pulsatile way: during systole. However, the need for oxygen and nutrients in the body is continuous, and could not depend on an only pulsatile supply: this is where the importance of the elastic vessels mentioned above comes in:

1. During systole a large amount of blood is pumped into the aorta. Its elastin allows it to expand, pushing 25% of the SV forward, and storing transiently 75% of the SV

2. During diastole the heart is not pumping anymore blood into the aorta, but the stored energy in this elastic vessel allows it to recoil, maintaining blood flow during diastole

3. Another systole starts and the cycle repeats itself

The Windkessel effect

The mechanical energy stored in the stretched elastin serves to maintain the blood pressure during diastole.

Describe how the mean blood pressure changes along the vascular system

Outline the effects of the autonomic nervous system on cardiac and vascular function

Define the term ‘coronary heart disease’ and describe the relationships between the major disorders of the cardiovascular system

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