Cardiac Physiology


  • The cardiac cycle is divided into two contiguous phases of ventricular diastole and ventricular systole. When we talk of cardiac systole we are concentrating on ventricular function mainly.
  • Loss of atrial systole predisposes you to cardioembolism as seen with AF. Loss of Ventricular systole means death.

Ventricular diastole: The time when the LV and RV muscular cavities relaxes and expands and the ventricles load with blood assisted by atrial systole. This is the filling time and any impediment to filling can cause impaired cardiac function. This can be seen with diastolic heart failure where the ventricle is too stiff like trying to blow air into a stiff balloon. If the ventricule cannot fill properly then it has insufficient blood to eject in systole. Diastole shortens as heart rate increases. Problems with ventricular filling are called diastolic dysfunction.

Ventricular systole: Systole is when the ventricle contracts and blood is forced out from the left ventricle into the aorta and from the right ventricle into the pulmonary artery. If this is impaired this is known as poor systolic function. Not all of the blood is foced out, usually about 70% and this is known as the ejection fraction. 

Cardiac Output

Cardiac output is the volume of blood ejected in each ventricular (both right and left ventricle eject approximately the same volume) systole of the cardiac cycle. Typical total blood volume is 5 L. The volume of LV at the end of diastole = 100 ml and volume in LV at end of systole = 30 ml so the stroke Volume (SV) is 70 ml, this is how the ejection fraction mentioned above is calculated i.e. 70/100. Average heart rate 70-80 bpm. The cardiac output for a minute is SV (70 ml) x Heart rate (70bpm) = approximately 5 L.

In practice there are various techniques for measuring Cardiac output. In practice these are research techniques. We rarely measure cardiac output outside the ITU but use surrogates such as blood pressure, urine output and exercise tolerance as indicators. Transthoracic cardiac echocardiography is a good determinant of systolic function but does not actually directly measure cardiac output.

  • Thermodilution technique using a PA catheter - cold dextrose is injected into the Left atrium and the temperature measured using a transducer in the pulmonary artery. The drop in temperature with time infers the volume of blood passing per unit time and so an estimation of cardiac output can be made
  • Oesophageal Doppler can visualise and measure using doppler the flow in the descending Aorta. Using a correction factor for the patients age, weight and height an estimation of cardiac output can be made. This can be used in ITU or peri-operation in selected individuals but other than that is not in common usage outside of the critical care setting.

Flow in blood vessels is under local and systemic constraints. Localised alterations to flow depends on localised resistance. Most of this is in arterioles and small arteries. Small changes in arterial radius can have large changes on peripheral resistance. Capillaries have a much less important role in altering flow patterns.

As described there is a systemic and pulmonary circulation. Both systems are both in parallel and in series so flow is the same through both. Resistance in pulmonary side only 10% of the systemic circulation. Systemic pressures 120/80 mmHg. Pulmonary pressures 25/10 mmHg

Physics for Circulation

Many of the concepts that you came across in your 'O' and 'A' level physics are useful in cardiology. A couple of concepts will make things a bit easier.

  • Blood pressure = Cardiac Output x Peripheral Resistance

This is similar to Ohm's law ( V=IR) and is basic physical law that applies to any flow situation from blood to current to air in a bronchus to water in your central heating. Note that blood pressure is the product of CO and PR. What is important is oxygen delivery and that is directly related to CO. So a low BP does not always mean low CO if the PR also drops. If PR is constant then BP is directly related to CO.

  • Cardiac output (per minute) = Stroke Volume per heart beat x Heart rate (per minute)

Doppler Effect

Doppler effect

Doppler is a very vital concept in cardiology and wherever flow is being measured. The concept is seen in normal life where a car or ambulance coming towards you has a higher frequency tone and once past the sound seems to be of lower frequency and falling. This frequency shift can help us to measure the velocity of the structure that moves as the speed of sound in air is fixed. Measuring the frequency of the wave coming towards you and its change can tell you the speed of the object. With blood flow the speed of high frequency sound across fluid filled tissues is standard. The sound waves bounce back of the moving blood and if the blood is moving towards the probe the resultant sound frequency is higher and if moving away is lower. The velocity of the flow can be calculated.

  • The formula is    f = f0 ( c+ vr)/(c+vs) and here f is the calculated frequency

  • vr is velocity of receiver e.g. moving blood cells
  • vs is velocity of source e.g. probe which is usually zero

Poiseuille's Law

The rate of flow of blood in a blood vessel can be described by Poiseuille's law. This is in a conduit with smooth laminar flow which is not always the case in a blood vessel. Flow in a pipe is from a location of high pressure to one of lower pressure. The pressure gradient P = P1 - P2. This is in practice the same as ohms law.

  • P = (P1 - P2) and Flow = 3.1415 x P x r 4/ 8 x viscosity x length

Note that flow increases as radius increases (to the fourth power) or viscosity falls or pressure difference increases or length of pipe falls. If you want to increase flow the most important determinant is the calibre of the pipe. This is how arterioles can responsively alter peripheral resistance by relaxing or constricting. It is also the reason that if you need to give fluids quickly you must insert a short and large calibre venflon.  

Coronary blood flow

As we mentioned in the anatomy section the first organ perfused by the cardiac output is the heart itself. Coronary blood flow is maximal in diastole and is zero during systole or even reversed. Diastole shortens with tachycardia which reduces time for coronary flow. The high wall tension in systole creates high resistance in the coronary vessels and this is worse with high muscle bulk and reduced flow such as aortic stenosis and HCM. Even at rest coronary oxygen extraction is maximal so only flow can increase oxygen delivery to match myocardial Oxygen demand. Coronary blood flow is not seriously compromised until there is a luminal narrowing of over 70%

Systemic blood flow

Flow through the peripheral circulation is from aorta to muscular arteries and then arterioles and then capillaries and then venules and veins and back to the heart. Note that most of the peripheral resistance in the circulation is generated at arteriolar level (about 40 mmHg fall) and not as many students think at capillary level (20 mmHg fall). The aorta and arteries contribute a drop of 25 mmHg in terms of vascular resistance. In fact the capillary network total cross sectional area and also surface area for diffusion is much greater than that at other levels and the capillary level resistance is low and so flow is slow allowing exchange of oxygen and other nutrients. Both systemic and pulmonary capillary beds are low resistance circuits. The factors that control flow are shown below.

Blood flows out of the heart in a pulsatile shot of blood into the aortic arch and so has to follow an arc with some blood going to arms, head and neck and then on to the descending aorta. The aorta is muscular but has a significant presence of elastic tissue which helps to store the recoil systolic energy and converts flow into a more continuous laminar flow supply of blood. The aorta has to stretch during systole and like a rubber band (potential energy) stores the energy as it then returns to its normal diameter transferring this energy back to the blood flow as kinetic energy. Flow dampens and continuous flow isn't really seen until arteriolar level. Initial flow velocity at aortic level is 20 cm/s and this falls to 0.05 cm/sec at capillary level which aids gas and nutrient exchange.

In the large veins flow can again become marginally pulsatile but this is simple reflecting right atrial pressures and not a reflection of LV pulsation. In total there is approximately a 100mmHg drop from aorta to right atrium. If we assume a cardiac output of 5-6 L/min then we can calculate resistance. R = Pressure drop/flow. Pressure drop across the whole pulmonary circulation is however only 10 mmHg for the same flow.

  • Systemic vascular resistance = 100 (mmHg) / 6 (L/min) = 17 mmHg/L/min
  • Pulmonary vascular resistance = 10 (mmHg) / 6 (L/min) = 1.5 mmHg/L/min

It is worthwhile just reflecting the low pressure and low resistance of the pulmonary system which is supplied by the force of the RV systole. Significant rises in the pulmonary vascular resistance can result in pulmonary hypertension and in those with congenital heart disease and shunts in Eisenmenger's syndrome.

Cardiac cycle

The Sinoatrial node drives the cardiac cycle. It has an intrinsic rate of 100 bpm but this is slowed by vagal tone to 70 bpm. The SAN pacemaker cell fires of an action potential into the surrounding atrial tissue.

Within atrial tissue the myocardial cells depolarise and the action potential spreads like a forest fire across the atrial generating a P wave on the surface ECG. The SAN lies within the right atrium and so it is the RA that depolarises first - atrial systole.

Assuming the previous beat was normal then the heart at this point will be near the end of ventricular diastole and the atrial contraction that is caused causes slight additional filling of the ventricles. This is the period of active ventricular filling which is lost with AF. Atrial systole adds 15% to ventricular filling. This becomes more important as heart rate increases and time for diastolic filling decreases.

The depolarisation reaches the AV node where there is temporary slowing of passage and this allows the heart maximal time for filling across the mitral and tricuspid valves. This continues as part of the PR interval.

The depolarisation spreads down the bundle of his and into the left and right bundles and purkinje fibres and spreads quickly across the myocardium. The surface ECG represents ventricular depolarisation as a QRS complex. As the ventricles contract there is a sudden rise in left ventricular pressures. The mitral and tricuspid valves shut tight (first heart sound) and there is isovolumetric contraction. Eventually the LV pressures exceed aortic and pulmonary pressures and the aortic and pulmonary valves open and blood is forced into the aorta. This is the ejection phase.

The ventricle then begins to relax and electrically repolarise. Pressure in the ventricles fall and the aortic and pulmonary valves shut (Second heart sounds). There is isovolumetric relaxation. The Mitral and tricuspid valves open and during this period of diastole there is a period of passive ventricular filling which is usually very rapid. The SAN then depolarises once more

During Diastole time allows coronary flow and ventricular filling. Diastole shortens with increasing heart rate

Cellular level

Pacemaker cells have no resting membrane potential but constantly leak current raising membrane potential rises until it hits the threshold potential. This is due to influx of calcium. The rate of change of membrane potential can be altered by extrinsic factors thus altering heart rate. Myocardial cells exist at a steady membrane potential unless depolarised. Depolarisation results in a rapid movement in though fast Na channels of Na ions.

This also opens calcium channels and calcium enters. This leads to the opening of Ca2+ channels in the sarcoplasmic reticulum which causes myocardial contraction. Calcium enters through L-type dihydropyridine sensitive channels on the sarcolemma which leads to calcium release from sarcoplasmic reticulum through RyR2 cardiac ryanodine receptor Excitation contraction coupling

Myocardial cells are surrounded by a membrane (sarcolemma) containing myofibrils surrounded by sarcoplasmic reticulum which form a T system of channels. The basis of excitation contraction coupling is the myosin cross bridge. Depolarisation leads to entry of Ca2+ ions into the sarcoplasmic reticulum. The 100 fold rise in cytosolic calcium saturates all the Ca2+ binding sites of troponin C which displaces tropomyosin uncovering myosin binding sites on actin. ATPase activity in the myosin head hydrolyses ATP to ADP. There is a conformation change in relation between actin and myosin which leads to movement or ratcheting such that the actin and myosin filaments slide past each other shortening the sarcomere.

Ratcheting continues as along as cytosolic Ca2+ is elevated but this soon drops as it is actively removed by a sarcoplasmic reticulum ATPase pump. Relaxation follows where troponin C releases calcium and a change in conformation that covers the active binding sites. The sarcomere returns to its initial length. Any increase in cytosolic calcium increases the amount of ATP hydrolysed and the force generated. Mechanism include beta-adrenocreceptor stimulation which increases cAMP which activates protein kinase which increases calcium entry through L-type calcium channels. Digoxin increases intracellular calcium levels. Excitation contraction coupling may be impaired in heart failure.

Determinants of flow

There has been a great improvement in the understanding of vascular flow. Even 20-30 years ago the endothelium was regarded as an inert barrier structure and it was only through research and the discovery of the effects of nitric oxide as a vasodilator that the endothelium was looked at and its importance recognised.

About 40 mmHg of the mean blood pressure of 100 mmHg is dropped across the arteriolar bed this is the place where flow is modulated. As we saw the flow depends on the Radius4 so controlling the vessels radius is the most expedient way to control flow and pressure. Arterioles structurally are composed of a layer of endothelial cells surrounded by a layer of smooth muscle.

Mechanisms of Control of arteriolar flow/vessel radius

  • Intrinsic Myogenic: Simple tonic contraction of the surrounding smooth muscle in response to stretch. The degree of response can vary in different circulations. These may be through stretch and activation and opening of calcium channels. This along with Sympathetic control would cause a degree of ongoing vasoconstriction and contribute to the underlying vasomotor tone. Can vary from second to second.
  • Metabolic autoregulation : A lack of blood supply leads to the build up of carbon dioxide and lactate with acidosis. These cause smooth muscle relaxation and therefore increase blood flow. Other local metabolic vasodilators include ATP, ADP, AMP, lactate and pyruvate and potassium. These mechanisms are found in heart, brain and gut.
  • Humoural control uses the release of chemical substances to alter local vascular tone

Vasoactive substances determine local blood flow and can be divided into constrictors and dilators

Vasoconstrictors include

  • Endothelin 1/2/3 on ETA and ETB receptors
  • Noradrenaline through alpha-1 receptors
  • Angiotensin II
  • Thromboxane A2

Vasodilators include

  • Adrenaline on beta-2 receptors
  • Nitric oxide
  • Prostacyclin
  • Endothelium derived hyperpolarising factor


During exercise or sympathetic stimulation there is an increased heart rate and stroke volume. Renal and gut and skin perfusion falls. There is increased muscle and cardiac perfusion. This is due to

  • Release of Noradrenaline and Adrenaline with skeletal muscle vasodilation through beta-2 receptors
  • Vasoconstriction to other major organs through alpha-1 mediated receptors
  • Increased heart rate and pulse rate and stroke volume through beta-1 receptors
  • Bronchodilation through pulmonary beta-2 receptors on bronchial smooth muscles

Physiological Effects

  • Heart rate 50/min → 150/min (x3)
  • Stroke volume 80 ml → 160 ml (x2) per systole
  • Peripheral resistance falls
  • Cardiac output increases by x 6 times from 4 → 24 l/min and even higher

Cardiology Concepts

Heart failure means insufficient blood being pumped out to emat the bodies demands despite a normal venous return. It can be due cardiac muscle disease and these can be grouped into systolic and diastolic. The difference is not well explained but is easy if you think about it

Systolic failure

This is usually easier to understand. Imagine a water pump which is working at half energy. It will pump less per unit time and in the heart this is usually seen as a reduced ejection fraction. Can be due to muscle death or muscle hypoxia and the inability to generate satisfactory myocardial contractility. The issue is the ability of the heart muscle contraction.

Diastolic failure

This is due to inability of the ventricular muscle to relax. Filling the left ventricle is a bit like filling a balloon with air. With a well stretched compliant balloon you don't need to puff to hard to fill it. However a new or other balloon will be much stiffer and filling will be difficult. The problem is relaxation of muscle fibres. The left atrium will have to work harder to get blood in which canbe seen as an increased LV end diastolic(filling) pressure. This is seen when the muscle is stiff and thick such as with severe LVH or HCM as well as older diabetic patients. Remember the balloon analogy - if because it is stiff and only half fills then there is going to be much less 'air' pumped out when you let it go and so there is failure. For diastolic dysfunction the management is largely diuretics and relaxants such as calcium antagonists.