Cardiovascular Physiology

Cardiac Electrical Activity

• Features of contraction:
- Must be electrically activated
- Produced by waves of excitation that spreads through the myocardium
- Occurs in an coordinated manner
- Each area stimulated at the appropriate time (not all at once)
- Systole is effective in propelling blood in circulation
• Loss of pattern: upsets in the electric activation will lead to impairment of heart pump such as atrial and ventricular fibrillation and consequently limiting exercise capacity and fatality respectively.
• Electrical properties of myocytes:
- Excitability
- Conductivity
- Automacity
• Excitability: ability of the cardiac muscle to depolarize and repolarize allowing transmission of action potential and stimulation of local contraction.
• Phases of action potential: 4 phases in a cycle of action potential determined by the state of the channel opening.
• Fast responsive cells: cardiac cells that can rapidly depolarize and transmit action potentials, e.g. atria and ventricular cells (working cells)
- Phase 0: upstroke of cell membrane with rapid depolarization from -90mV resting potential. Threshold is at -70mV and opening of sodium channels causes large inward surge of sodium current down their electrical and concentration gradients (iNa). As membrane approaches sodium equilibrium potential, Na+ channels inactivates and only opens until next depolarization.
- Phase 1: transient repolarization to around 0mV by outwards potassium current (ito)
- Phase II: plateau and stable cell potential as the inward calcium current (iCa) through the L-type Ca2+ channels and CICR is balances the outwards potassium current (iki). The sodium channels are inactive causing cell refractory
- Phase III: repolarization with predominantly outward potassium current. Current iK is activated by a delayed response, e.g. channels stimulated to open during the depolarization phase but delayed to hyperpolarize later. Current iK1 is reactivated later when the membrane potential drops
- Phase IV: resting membrane potential with high conductance for potassium (iK1)
• Other potassium channels: these are involved during phase 3
- iK,ATP: open and close depending on levels of ATP, i.e. a decrease in intracellular ATP will activate iK,ATP. This allows shorter AP
- iK,Ach: acetylcholine dependent channels that is activated with increase concentration of acetylcholine or adenosine
• Other channels and pumps: functions to maintain resting potential or contribute to depolarization or hyperpolarization
- Ca pump: outward current (hyperpolarizing)
- Na+/Ca2+ exchanger: 3 Na+ in for 1 Ca2+ out hence net positive current inward (depolarizing)
- Na+/K+ ATPase: 3 Na+ out for 2 K+ in hence net positive current outwards (hyperpolarizing)
• Slow responsive cells: cardiac cells that depolarize and conduct action potential at a slower rate. These include cells of the sinoatrial node and atriaventricular node
• Distinguishing features of slow responsive cells:
- Resting potential is -55mV (much less negative than fast) which is already beyond the sodium channel threshold hence Na channels (present or not) can not be activated due to refractoriness
- Phase 0 has a much slower upstroke caused by inward Ca2+ current rather than Na+
- Phase 2 is not a plateau but slow repolarization and progressive decline in membrane potential
• Refractoriness: inability of the cardiac cell to be stimulated or excited
- Absolute refractory period: ending of phase 0 to beginning of phase 3 in which the membrane cannot be re-excited no matter the means, i.e. sodium channel fully closed and gated
- Relative refractory period: end half of phase 3 in which action potential can be stimulated by required a much larger stimulus than normal
- Supernormal period: first half of phase 4 in which the membrane is extremely excitable and a weaker-than-normal stimulus are able to produce a slow propagating AP.
- Full recovery time: from beginning of absolute refractory period to the end of supernormal period showing the period in which cardiac cells undergoes electrical activity.
• Clinical significance of refractoriness:
- Prevents tetanizing of the heart
- Electric shock during RRP or SNP can cause stimulation to cardiac cells and distort pattern of contraction leading to fibrillation and death
• Interval-duration relationship: duration of AP is determined partly by preceding diastolic interval and faster heart rate means shorter AP.
• Conductivity: cardiac cells are able to transmit action potential through intercalated disk that electrically and mechanically coupled with each cells. Electrical activation and depolarization spreads throughout the myocardium from cell to cells.
• Electric properties of cardiac cells:
- Non-neurogenic: cardiac cells do not contract in response to neural signal. Nerves are present not to initiate contraction but to regulate the force and rate.
- Myogenic: heart muscles self-contract with AP initiated at the pacemaker (SA node)
• Electric syncytium: the cardiac cells are arranged in a laminar network of electrically connected cells
• Automaticity: ability of the cardiac cells to initiate an electrical impulse on their own through pacemaker activity or diastolic depolarization. Occurs in:
- SA node
- Cells around AV node
- His-Purkinje network
• Pacemaker depolarization: slow depolarization to threshold through a combination of decreasing outward current to increasing inward current
- Outward current: iK
- Inward current: main if sodium current which is activated when the cell repolarizes and iCa a slow Ca2+ current that makes only a small contribution to early diastolic depolarization and extends into diastole
• Ways of altering pacemaker discharge rate:
- Change rate of depolarization: slow depolarization means longer time to reach threshold and longer duration of a beat
- Change of threshold level: increasing threshold means longer time for the depolarizing membrane potential to reach and so slows the discharge rate
- Change ending level of repolarization: lower the ending resting potential, the longer it takes to depolarize to the threshold and hence slowed discharge rate
• Effect of autonomic system:
- Parasympathetic: slows the heart rate by release of acetylcholine at vagal ending in the heart which increase K+ permeability of SA cells (iKAcet, current) and thus hyperpolarize and decrease pacemaker slope of depolarization (i.e. greater outward current). Further effect includes slow conduction through or block AV node.
- Sympathetic: speeds heart rate by release of noradrenaline at SA node which increases the slope of pacemaker depolarization
• Cardiac activation sequence:
- SA node: spontaneous depolarization around a small area of specialized tissue in right atrium wall at 70 beats per minute. Cells are continuous with neighboring myocardium
- Internodal tract: cells connected and aligned with rapid conduction
- Atria: AP spreads through muscle cells via gap junctions with contraction of atrium
- AV node: slow conduction velocity of 0.05ms-1 that allows a delay between atrial and ventricular systole, giving time to fill up the ventricles
- Bundle of His: the only electric pathway that extends from AV node to ventricles. Myocardium of the atrium and ventricles are insulated by fibrous skeletal rings that surround the valves. Discharge rate 40 – 55 bpm.
- Bundle branches: bundle of His splits into right and left bundle branches
- Purkinje fibres: bundle branches split into the purkinje fiber network which ramifies over endocardial surfaces and rapid conduction (2-4 ms¬-1) lets ventricles contract in synchrony. Discharge rate 25 – 40 bpm.
- Ventricles: action potential spreads through myocardium and excitation travels from endocardium to epicardium with contraction of ventricles
• Control of pacemakers and conduction:
- SA nodes is not the only automatic tissue in heart but it acts as the pacemaker because it has the highest intrinsic rate and this leads on to overdrive suppression of other pacemakers (rapid rate of action potential overwork channels and pumps and so slows depolarization)
- Loss of SA node function will be replaced by other pacemakers
- Slow conduction in AV node
- Rapid conduction in purkinje network to pump ventricle synchronously for efficiency
- Conduction rate is determined by radius of fibers and rate of depolarization, e.g. AV node has small radius and slow response cells hence slow conduction
• Wolff-Parkinso bvn-White syndrome: presence of alternative abnormal electrical pathway between the atria and ventricles through extra muscular connection around the valves which causes:
- Pre-excitation of ventricle contraction before “proper” action potential
- Recycling of action potential back to the atria from ventricles (re-entrant arrhythmia) to re-excite myocardial tissues that has repolarized (independent of the pacemakers)
• Treatment of WPW:
- Rubbing the baroreceptors to slow heart rate and AP discharge rate and diminish circulating AP
- Exercising heart muscles

The Normal Electrocardiogram

• Electrocardiogram: recording of the electrical activity that spreads through the heart from the body surface using electrodes. A measure of voltage change over time.
- Electrode are not touching the heart but at different site of body
- Measures the potential difference between the sites
- Body tissue are conductors so electrodes can be placed at a distance from the heart
• ECG waves:
- P waves: atrial depolarization which has a relative small positive deflection and slow event
- PR segment: isoelectric event reflecting the time for action potential to pass through AV nodes and His bundles (electrical activities too small to be recognized)
- QRS complex: ventricular depolarization that is of a greater magnitude than P wave due to mass, shorter length due to rapid conduction of Purkinje fibers. Atrial repolarization is overshadowed
- ST segment: isoelectric plateau of ventricular action potential with cardiac cells all depolarized
- T wave: asynchronous ventricular repolarization with a positive deflection as repolarization occurs from epicardium to endocardium (endocardium has longer duration of AP than epicardium)
- PR interval: Reflects total time for wave to pass from atria to ventricles
- QT interval: reflection of ventricular action potential duration
• Dipole and vector representation of ECG: direction of the action potential propagation can be visualized as a wave front of localized depolarization moving from negative terminal to positive terminal of a dipole (arbitrarily designated), i.e. vector direction is “-“ to “+”.
- Dipole: pair of equal but opposite charges separated by a small distance
- Electrodes representing two dipole terminals will measure the electric field and activity in between
• Dipole projection: the original electrical pathway of the action potential can be mapped by a lead line, i.e. a vertical lead line will demonstrate the projection of the component and activity of the cardiac action potential in the vertical plane.

• QRS representation with ECG:
- Q: ventricular septum depolarizing (action potential goes horizontal to the right so toward negative terminal hence negative deflection)
- R: ventricular apex depolarizing (AP travels down the septum toward the positive terminal so positive deflection)
- S: ventricular base depolarizing (AP migrates up through the ventricular walls towards the negative terminal so negative deflection)
• ECG lead system: a single dipole is overly simplified and does not provide a holistic representation of the cardial electric activities. Hence multi-dipoles are used with potential differences measured between many sets of electrodes (leads) and mapping out components of the action potential. There are three types of leads:
- Limb leads
- Augmented limb leads
- Precordial leads
• Limb leads: limb leads measures potential difference between two electrodes (bipolar system) for any combination of the right arm, left arm and left leg. These three locations represent an equilateral triangle (Einthoven’s triangle) with the heart at the center. Components of the cardiac dipole in the same direction as the leads line will be projected on to them an recorded

- Lead I: LA - RA
- Lead II: LL - RA
- Lead III: LL – LA
- Einthoven’s law: at any instant during the cardiac cycle, I + III = II
• Unipolar limb leads: by connecting all three limb electrodes together through resistors, a leads (electrode) of a constant value is created and arbitrarily assumed to be zero. Using another electrode (exploring electrode) which can be placed in any location on the body and the potential difference is calculated in relation to the reference point.
• Augmented unipolar limb leads: as the registered voltage from the unipolar leads is too small, an alternate arrangement of electrode is devised to increase perceived signal. Result is an approximate 1.5 times increase.
- aVR lead: leads of the left arm and leg are connected to form the negative terminal while exploring electrode is placed on the right arm
- aVL lead: leads of right arm and foot act as one terminal and electrode on the left arm is another
- aVF lead: leads of foot measured in conjuction with united leads of left and right arm
• Unipolar chest leads (precordial): set of 6 leads (V1 to V6) placed around the chest (front to side) that measures the electrical activity of the heart in the horizontal plane.
• 12-lead ECG: in total there are 6 leads in the frontal plane called a hex-axial system and 6 leads in the horizontal plane. Usually only the pattern of one lead is used to create a rhythm strip (cycles of recorded heart activity for that strip)
• Instantaneous cardiac vector: using any two leads, the cardiac electrical vector can be derived for that particular time. Third lead can be used to confirm the result.

• Mean QRS vector: the representative pattern and direction of the action potential of the heart as it passes from the base to the apex. Calculated using Eindhoven’s triangle:

-
- For each lead, the difference between the positive and negative deflection are calculated and plotted on the triangle. From the components, the mean vector can be derived
- Normal mean QRS deflection is from -30o to +110o. Great cardiac mass will influence vector direction of the electrical activity toward its direction. E.g. smoking causes right axis deviation as it destroys lung vessels and increase blood resistance and consequently right ventricles undergoes hypertrophy to compensate.

Cardiac Rhythm Disturbances

• Conduction: electric impulse is initiated at the SA and spreads through the right atrium and penetrates the interventricular septum. AP transmitted from endocardium to epicardium via the purkenje fibers
• Intrinsic depolarization rate: SA nodes 60-70/mins, AV junction 35-50/mins, ventricles 30-40/mins
• Consequence of electrical problems: heart rate being too slow and too fast and the consequences can range from no symptoms to death.
- Rhythmic disturbances due to drugs prescribe, e.g. beta blockers given for angina and cause slow pulsation (slow SA)
- Breathlessness
- Fast heart rate can be restored by a defibrillator
• Sinus node disease:
- Sinus arrest
- Sinus bradycardia
- Atrial flutter
- Atrial fibrillation
• Sinus bradycardia: ECG demonstrates inverted T-waves (signs of ischemia)
• Recurrent syncope: repeated loss of consciousness due to lack of oxygen to the brain. This is can be caused through arrested sinus node or carotid sinus input problem, i.e. too low pressure leading to vagally mediated black out.
- ECG indicate slow depolarization and eventually cessation
• Tachycardia: excessive rapid heartbeat (usually over 100 beats per minute)
- Treatment involve use of adenosine to block AV node so even with rapid depolarization of atrium, ventricles will not respond
- Using ventricular defibrillation
• Treatment of sinus node disease:
- Removing offending causes
- Find stimulants
- Pacemaker devices
• AV block: blockage of AP conduction from atrium to ventricles usually due to either delay through the AV node or getting to his bundle, i.e. SA to AV, AV, AV to His
- First degree heart block: prolonged PR interval (longer than 0.3 seconds)
- Second degree heart block: type I and type II non–conductive problem. On ECG, QRS waves doesn’t happen for several SA stimulations
- Third degree heart block: non-coordination of ventricle contraction with atrium, i.e. atrium just beating and ventricles responds occasionally. This produces cannon waves on the ECG and consequences include reflux of ventricular blood during systole so lower efficiency and cardiac output. Patient feels tired, breathlessness, dizzy and slow pulse.
• Causes of AV block:
- Idiopathic / degenerative
- Myocardial infarction
- Cardiac surgery
- Infiltrative and inflammatory cardiac disease
- Drugs, e.g. digoxin, beta blockers, calcium channel blockers. Exception of ACE inhibitors

Heart as a Pump

• The cardiac cycle: during each heart beat, the cardiac chambers go through a series of repetitive events to co-ordinate systole and diastole. The events are:
- Atrial systole
- Isovolumic contraction
- Rapid ejection
- Reduced ejection
- Isovolumic relaxation
- Rapid filling
- Reduced filling
• Atrial systole: occurs soon after atrial depolarization (p-wave). Atrial contraction causes pressure to exceed that of ventricular pressure, making the last effort to fill the ventricle. Ventricular filling is usually passive but at high heart rate, time for filling is short so atrial contraction becomes important.
• Isovolumic contraction: initiated with the peak of the QRS waves. Ventricles contract and pressure exceeds atria causing the AV valves to close (1st heart sound) but still below that of vessel pressure so aortic valve remain closed. Ventricle volume hence remains constant.
• Rapid ventricular ejection: as ventricular pressure rises above the greater vessels, semilunar valve opens and ventricular outflow of blood peaks with rapid decrease in ventricular volume. Atrial pressure drops to minimum.
• Reduced ventricular ejection: ejection phase coming to an end with a decrease in ventricular pressure, which is followed closely by aortic pressure. The aortic pressure is slightly above that of the ventricular pressure to continue to propel the blood forward. Atrial pressure rises with filling. Final ejection fraction is around 55 to 75% and end-systolic volume is 60 mL.
• Isovolumic relaxation: as the ventricle relaxes, rapid pressure fall dropping to below that of the vessel pressure. Semilunar valves closes immediately to prevent backflow of blood (2nd heart sound). Recoil of blood on to the valves produces a dicrotic notch in the aortic pressure curve with partial regurgitation (negative ventricular outflow). As the ventricular pressure is above that of atria, AV valve remain closed so ventricle relaxed with constant volume.
• Rapid filling: when ventricular pressure drops below atrial, the AV valve opens and rapid filling occurs. Ventricular volume increases and occasionally a 3rd heart sound can be heard.
• Slow filling: pressure of the ventricle increases with blood and eventually equalizing with that of atria. Blood flow slows.
• Dynamics of the heart: using an echocardiogram, the wall thickness and valve motion can be monitor to observe cardiac movement and abnormalities. Wall thickening shows decrease internal volume hence ejection while decrease gap of valve shows closure.
• Differences of events in LV and RV:
- Pressure of right side of the heart is always lower than that of left side due to different resistance encountered.
- Timing of pulmonary valve closure is delayed with inspiration (more blood drawn into the RV) hence splitting of the 2nd heart sound occurs.
- Mitral closes before tricuspid and tricuspid opens before mitral (due to relative lower LA pressure); pulmonary valve open before aortic and aortic closes before pulmonary (due to relative lower pulmonary pressure)
- RV valves open sooner and close later as result of electrical activation and pressure differences.
• Heart sounds and murmur:
- 1st heart sound: produced from closure of AV valve, deceleration of blood and tensioning of AV valve and chordae with leads to oscillation of blood and chamber walls.
- 2nd heart sound: produced from semilunar valve closure, and higher frequency oscillation of blood, tensed vessel walls and valve.
- 3rd heart sound: produced from rapid entry of blood into ventricles causing wall vibrations during early diastole. This is normal in children and can be used to indicate pathology
- 4th heart sound: oscillations and stretch caused by atrial contraction
- Murmurs: due to rush of blood such as aortic stenosis or mitral regurgitation
• Pressure measurement: flow of blood through the pulmonary circuit is due to the difference of RV pressure to LA pressure.
- Using fluid filled catheter and pressure transducer
- LA pressure is obtained using a catheter with a balloon on the end. Catheter is passed from veins into the RA, RV and pulmonary artery in which the balloon wedges and blocks the vessel. Pressure measured of the blood is thus representative of LA. This is called pulmonary capillary/arterial wedge pressure
• Measurement of cardiac output: using Fick’s method
- The oxygen content at the arterial end and venous end of the pulmonary capillaries is measured. The difference shows the increase in oxygen content gained.
- Knowing the oxygen uptake rate through measuring expired oxygen content allows rate of blood flow to be calculated, i.e. if oxygen content increase is normal but flow rate is increased, the oxygen uptake rate must also increase to maintain the level of oxygen content.
- The equation is:

[O2]pv¬ is measured in arterial blood from needle puncture while [O2]pa is measured by a catheter advanced into PA
• Criteria for Fick’s methods:
- Mixed venous blood essential as different organs have different extraction. So must be collected after RV
- All of the measured substance must be collected
- Steady state must exist, ventilation and cardiac output.
• Dilution method: using the rate of dilution to calculate cardiac output
- Thermodilution: injection of cold saline into the blood of the RA and measure downstream temperature using a sensor at the pulmonary trunk. Slower flow rate will confer a lower time period of temperature decrease as the saline would have increased to that of the body temperature
- Advantages: no arterial puncture, no toxicity, and no recirculation (problem for dye dilution)
• Vascular resistance:
- Total peripheral vascular resistance: where SA/SV represent systemic artery/vein
- Pulmonary vascular resistance: where PA/PV represent pulmonary artery/vein
- Resistance changes in diseased state, e.g. emphysema causes much of lung tissue to be destroyed so vascular resistance is high with loss of parallel networks. To maintain flow, RV experience a higher pressure load so undergoes hypertrophy and eventually RV failure

Ventricular function

• Stroke volume: end diastolic volume – end systolic volume
• Cardiac output: heart rate × stroke volume
• Passive filling: shape of an exponential curve. The volume of ventricles increases with a little pressure due to compliance. But as the fibres stretches beyond its limit, the force needed to further increase the volume increases greatly.
• End-systolic PV relationship: during systole, the pressure volume relationship is linear, as the pressure the heart is capable of developing is proportional to the volume
• Pressure volume loop:
- Due to performance limit, the pressure of the heart can never be higher than the systolic pressure at each volume.
- Potential pressure: the difference between the pressure in diastolic filling and systole at each volume
- Event one: stroke volume fills from ESV to EDV along the passive PV curve
- Event two: pressure increase vertically due to isovolumic contraction along the potential pressure line
- Event three: before the pressure reaches the maximum systolic pressure for EDV, the aorta valve will open causing volume to decrease while the pressure remains fairly constant. The volume will decrease until the heart can no longer develop the pressure to eject blood and this is the ESV.
- Event four: isovolumic relaxation cause pressure to drop vertically down to that of diastolic curve.
• Preload: end-diastolic volume (stretch of muscles before contraction)
- Determines the degree of overlap of the filaments
- With increased preload, the maximum potential pressure also increases allowing greater volume to be ejected (stroke volume) – Frank-Starling Mechanism
- The PV loop extends horizontally to the right
• Afterload: pressure at which the valve opens (pressure the ventricle must contract against to eject blood)
- Determined by the systolic and aortic pressure
- Increased afterload result in a reduction of stroke volume as ESV increases (lower volumes not possible as heart can’t develop the pressure to eject blood). This usually indicate sick cells and heart failure
- PV loops extends vertically upwards
• Inotropic states: alters the slope of the PV line for systole, i.e. varies the maximum active tension/pressure at which the heart can generate at each volume
- Contractility is varied depending on the Ca2+ in the myocyte
- Increased inotropic state allows for increased stroke volume as at a lower ESV, the same pressure can still be developed to overcome the afterload.
- PV loop extended to the left and upwards for increased inotropic state
• Chronotropic states: heart rate.
- Increased heart rate is the result of more depolarization per second so amount of Ca2+ in cytosol increase as pump stays constant. Thus stronger contractility (minor inotropic effect)
- Increased HR will increase cardiac output but at the same time it reduces the time for ventricular filling so reduced stroke volume.
- PV loop shifts just like inotropic effector
• Balancing function of left and right heart: the cardiovascular circuit is closed so both of the heart must essentially pump the same volume. The heart must respond to changes to maintain same output.
- Increase in afterload will cause the stroke volume to decrease
- Decreased stroke volume will cause the blood to accumulate in the lung
- During next filling the EDV will increase and since the heart is at a greater volume, it is able to produce a greater pressure and restore the stroke volume
- Overall the PV loops shifts to the right and operate at a higher pressure/volume load
• Factors that affect preload:
- Blood volume
- Venous tone (SNS and vasoactive drug): increased tone can push more blood
- Posture: gravity reduce preload when standing up
- Diastolic interval: time needed to fill depends on heart rate
- Atrial contraction: provide extra boost
- Muscles pump: decreased muscle contraction will decrease venous return
- Intrathoracic pressure: decreased pressure draws in blood
- Intraperiocardial pressure: stretch receptors
- Ventricular compliance: increased compliance means easier filling
• Factors that affect afterload:
- Systemic pressure: hypertension
- Vasoconstriction: vascular resistance
- Aortic stenosis: resistance from narrowed valve
- Ventricular geometry: wall stress
• Factors that affect inotropic state:
- Sympathetic nervous system: catecholamine
- Force-frequency relation
- Action potential changes
- Cardiomyopathy: decreased inotropic state due to cell death
- Positive inotropic drugs: isoprenaline
- Cardiac depressant drugs: anti-arrhythmics
- External ion concentration
• Factors affecting heart rate:
- ANS: reflex centers
- Hormone: circulating catecholamines
• Assessment of ventricular performance:
- Ejection fraction: percentage of EDV ejected by the heart, i.e. stroke volume / EDV. This is usually measured using echocardiography. Normal LV ejection fraction is around 55% when normal and 85% when exercising.
- Measurement of contractility: maximum rate of rise in ventricular pressure during ejection
- End systolic PV relation: useful indicator of ventricular function. At any heart rate, the pressure of end-ejection will always arrive on the line
• Ventricular function curve:
- Stroke volume comparison: preload plotted against stroke volume. Good function means a continuous linear relationship before dropping off (i.e. exceeds the heart’s capacity to pump out blood). This approach however is susceptible to change in afterload.
- Stroke work comparison: preload plotted against stroke work. Minimally affected by afterload as increased MAP will decrease SV but SW will stay the same.
• Stroke work: total work done by the heart to pump out the stroke volume of blood. It’s approximately by the product of mean arterial pressure times stroke volume.
- Increased preload will increase ventricular output
- Stroke work changes in response to inotropic drugs (shifts curve to left due to positive inotropic drug)
- Stroke work takes into account preload, afterload, inotropic state so is a effective way of summarising heart function

Vascular Function

• Fluid dynamics: flow rate is proportional to the driving pressure gradient and inversely proportional to effective resistance.
where Q is volume rate of flow (Lmin-1) and R is hydraulic resistance
• Pressure gradient: measured as the difference between arterial and venous.
- In the aorta, blood flows in a pulsatile manner. The walls stretch to stores elastic energy and recoils to maintain forward flow (Windkessel effect)
- Pulses becomes smooth distally with drop in pressure
- Overall the pressure drops in a sigmoidal fashion with little change through the large arteries, huge drop through small arteries and arterioles and steady pressure in venous section.
• Resistance: main resistance occurs in the precapillary resistance vessels. Increase in resistance in a particular set of vessel will reduce the flow to that area allowing control.
• Poiseuille’s Equation: where R is resistance is (η is viscosity, l is length and r is radius)
- Viscosity: disease can cause changes in blood viscosity such as polycythemia and cause blockage in blood flow.
- Length: resistance increases with length
- Radius: resistance is very sensitive to radius
• Laminar flow: flow velocity arranged in a parabolic profile with maximum velocity in the middle and zero velocity at the edge.
• Rigid vessels: small arterial resistance vessels with thick muscular walls (non-expansile). Most important in flow resistance relationship as their properties are most accurately modelled.
• Newtonian fluid: homogenous fluids in which their viscosity is unaffected by shear rate. However blood is not homogenous and consists of 50% cells. Its viscosity will change with shear rate
• Viscosity: measure of friction between adjacent layers of fluid as they slide over one another
- Shear stress: the force per unit area producing the sliding action between “layers” of fluid
- Shear rate: a velocity gradient per distance between layers of fluid
- Relationship: shear force is directly proportional to shear rate as a greater force is require to cause the velocity to differ by a greater degree between layers. The proportionality constant that relate the two is viscosity

• Relative viscosity: ratio of the fluid viscosity to that of water, blood is around 2 – 15 times more viscous
• Factors causing different viscosity:
- Temperature: as temperature decreases, viscosity rises
- Haematocrit: the ratio of red cell volume to total blood volume. As haematocrit increases, viscosity increases and flow drops. This can be seen in polycythemia of people living in high altitudes
- Shear rate: at very low velocities, the cells aggregate and hence viscosity increases making it non-newtonian.
- Vessel diameter: at low vessel sizes, the viscosity decreases due to axial streaming (orderly movement of red cell along a line to reduce friction)
• Flow in distensible vessels: increasing pressure in vessels will alter vessel diameter. As a result, increase transmural pressure will increase pressure gradient but also vessel radius, which decreases the resistance and enhance flow
- Non-linear relationship between pressure and flow rate as resistance progressively decreases with higher pressure
• Vessel diameter and flow rate: flow rate is inversely related to vessel diameter. Hence in peripheral circulation, the large cross-sectional area of capillary produces low velocity flow which is good for gas exchange
• Shear stress: stress experience by the vessel wall due to the forces induced along the direction of the flow. Magnitude of stress depends on viscosity and rate of flow.
- The stress can cause damage to endothelium and eventually lead to weakening of the vessel wall
- Damage is countered by vessel wall response in which nitric oxide from the endothelial cells is released and these cause surrounding smooth muscles to relax and dilating the vessel to give a reduced flow velocity.
• Turbulent flow: when flow of fluid develops swirls and eddies, i.e. mixing of layers. The result is the flow rate becoming proportional to the square root of pressure.
Vascular Mechanics:

Blood Pressure

• Hydrostatic pressure:

Where ρ is density of fluid, g is acceleration due to gravity and h is distance below the surface

- With calculation of the blood pressure, the RA is the reference point.
- Total pressure: vascular pressure of heart PLUS local hydrostatic pressure.
- At the heart: venous pressure is 0 and arterial pressure is 90 mean.
- At feet: additional 90 hydrostatic gives 180 mmHg arterial and venous is 90 mmHg
- At raised hand: subtracting 50 mmHg gives 40 mmHg arterial
• Bernoulli’s Principle: total energy of laminar flow without resistance is constant and equals to the sum of:
- Pressure energy (P×V)
- Gravitational energy (mgh)
- Kinetic energy (1/2mv2)

- As a result, when there is a narrowing in a vessel, velocity increases to maintain flow rate so kinetic energy increases. Pressure must drop.
- In reality E is lost through a tube
• Effect of gravity on rigid U-tube flow:
- Horizontal: no effect of gravity pressure so pressure of pump decreases constantly throughout the tube until zero (with half pressure half way)
- Vertical: pooling of fluid half way causes increase in pressure but decrease to zero at the end
- Vertical inverted: pressure against gravity means at half way, the pressure is much lower and continue to decrease to zero at the end.
• Effect of gravity on distensible U-tube flow:
- Horizontal: same effect
- Vertical: as a result of increased hydrostatic pressure, the region at bottom will stretch (vessel of your feet) causing decrease resistance but also pooling of fluid. The effect of pooling is greater meaning pressure and flow back up is less (reduced venous return and preload). This is the key cause of orthostatic hypotension.
- Vertical tube inverted: negative pressure at top of tube due to gravity causing the tube to collapse. Flow to upper part will stop causing pressure to rise until enough to counteract the gravity and start flow again.
• Physiological implications:
- Heart valve closure: rapid blood flow through the partially closed leaflet will decrease pressure causing the valves to suck together (shut)
- Delayed valve closure: near the end of ejection, pressure gradient of LV and aorta is reversed however blood continues to flow forward due to KE difference and blood in ventricles has higher total energy
- Aortic stenosis: turbulence with narrowing meaning greater KE near the coronary ostia and lower pressure. This leads to poor coronary perfusion.
• Arterial pressure: MAP = PD + 1/3 (PS-PD) where PS is systolic pressure and PD is minimum pressure.
- Pulse pressure: PS – PD
• Mean arterial pressure:
MAP - CVP = CO × TPR
CVP is approximately zero hence MAP is controlled by CO (heart output) and TPR (vascular resistance)
• Determinant of pulse pressure:
- Stroke volume: increase stroke volume will required increased systolic pressure
- Aortic compliance: increasing compliance means decrease systolic pressure needed for same stroke volume
- Diastolic flow: rate at which pressure drops in artery. Vasoconstriction will increase TPR and decrease runoff rate leading to higher PD
- Heart rate: increased HR decreases run off time and so increase PD.
- Compliance of systemic arteries: stiffer arteries are unable to absorb the pressure and blood passes directly through causing increased blood velocity and decreased pressure.
• Peripheral artery waveform: radial stretch of ascending aorta by LV ejection initiates a pressure wave that propagates through the system.
- Pulse is a pressure wave (not blood flow)
- Pressure pulse travel faster than blood with stiffer vessels producing faster velocities (old people and distal muscular arteries)
- Less viscous the blood the faster the pulse travels
• Variations of pulse waveform: a dynamic system where.
- High frequency component damped (due to viscoelasticity) then disappear
- Systolic peak narrowed and elevated (pressure waves can bounce off bifurcation and constructively interfere or destructively superimpose leading to varied notches. Waves also travel at different speed due to wall compliance)
- Hump may appear in diastolic part probably due to reflection of the primary systolic waves.
• Measuring blood pressure:
- Auscultatory method: when pressure > systolic, no sound is produced (complete occlusion). When pressure < diastolic, no sound due to laminar flow. Between these two limits, blood will squirt through a partially occlude artery produce turbulence and korotkoff sounds.

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