CIRCULATION VIVAS
The Heart
2011-1
Describe the normal sequence of electrical excitation of the cardiac conduction system and
cardiac muscle? (+ 2006-2)
SA -> radially through atria -> AV node -> Bundle of His -> Major bundle branches (L) and (R) ->
Purkinje fibers -> ventricular muscle: septum to apex, then up to AV grooves. Spread is from
endocardial to epicardial surfaces
What are the common mechanisms which cause abnormalities of cardiac conduction? And…
What are the possible clinical consequences of these conduction abnormalities?
1. Abnormal pacemakers
- ectopic beats
- pacemaker failure (sick sinus syndrome)
- fibrillation (atrial or ventricular)
2. Re-entry circuits
- atrial flutter
- other tachyarrythmias
3. Conduction defects
- heart block
- bundle branch blocks
4. Prolonged repolarisation
- long QT (increased vulnerability to ventricular arrythmias/sudden death)
5. Accessory pathways
- WPW (Bundle of Kent) and LGL (short PR) -> SVT
2010-2
Please draw a normal ECG tracing
Describe the cardiac events that relate to each of the intervals
Cardiac cycle:
PR
R to
end of T
End of
T to P
Phase 1
Phase 2
Atrial systole
Isovolumetric vent.
contraction
Phase 3
Ventricular ejection
Phase 4
Isovolumetric Vent.
Contraction
Ventricular filling
Phase 5
Atrial systole
Ventricluar
systole
Diastole
The Action Potential:
R wave
S wave
ST segment
T wave
T-P
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
Rapid depolarization
Rapid repolarization
Plateau
Slow repolarization
RMP
Na influx (fast)
Na innactivation
Ca influx (slow)
K efflux
Nil
What is the electrophysiological basis for
elevation
acute
MI?
R ST
wave
Phase 0in(Na
influx
S wave
Phase 1
Defect in infarcted cells
Rapid repolarization
Decreased resting
membrane potential
Delayed depolarization
Cause
Accelerated K+
opening
Loss of
intracellular K+
Current Flow
Out of infarct
ECG change
ST elevation
Timing
Lasts minutes only
Into infarct (diastole)
TQ depression
( = ST elevation)
ST elevation
Minutes -> days
Out of infarct
After 30mins -> days
2009-2
Draw an ECG trace and identify the 5 phases of the cardiac contractile cycle. Also
demonstrate the ventricular volume trace.
Cardiac Cycle:
1. Atrial systole
2. Ventricular isovolumetric
contraction
3. Ventricular ejection
4. Ventricular isovolumetric
relaxation
5. Ventricular filling
2008-2, 2006-1
Please draw a normal ECG tracing, showing the durations of the major intervals
Intervals
PR
0.18
QRS 0.08
QT
0.4
ST
0.32
How
does
the ECG change with hyperkalaemia?
1. K+ 7.0: Tall peaked T waves
2. K+ 8.5: Loss of atrial activity, widened QRS
3. Extreme: Arrhythmias (VT and VF), then unexcitable (sinusoidal)
How does it change with hypokalaemia?
Long PR, ST depression, T inversion, U-wave
2007-2, 2005-2
Describe or draw an action potential in ventricular muscle
What are the ion fluxes that produce this action potential
How does the ECG relate to the ventricular muscle action potiential
The Action Potential vs ECG:
R wave
S wave
ST segment
T wave
T-P
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
Rapid depolarization
Rapid repolarization
Plateau
Slow repolarization
RMP
Na influx (fast)
Na innactivation
Ca influx (slow)
K efflux
Nil
Why does tetany not occur in cardiac muscle 2005-2
- Because of the inactivation of the sodium channels and the
prolonged action potential, cardiac muscle cannot contract in
response to a second stimulus until near the end of the initial
contraction
- During phases 0 to 2 and about half of phase 3 (until the
membrane potential reaches approximately –50 mV during
repolarization), cardiac muscle cannot be excited again; that
is, it is in its absolute refractory period
- It remains relatively refractory until phase 4
- Therefore, tetanus of the type seen in skeletal muscle cannot
occur
- Of course, tetanization of cardiac muscle for any length of
time would have lethal consequences, so it is a safety feature
2009-2, 2008-2, 2007-1, 2006-2, 2003-1
Describe the features of the action potential in cardiac pacemaker tissue
- Rhythmically discharging cells with a membrane potential, that after each impulse declines to the
firing level: the prepotential or pacemaker potential triggers the next impulse.
1. Prepotential: Initially IK efflux declines. Then Ih channels open
(following hyperpolarization) “funny” channels that pass both K+ and
Na+. Completed by Ca2+ influx via T (transient) channels
2. Action potential: due to Ca2+ influx via L (long-lasting) channels
3. Repolarization: due to K+ efflux – no plateau
Describe the major differences between a cardiac myocyte AP and the pacemaker
1. Fast Na+ depolarizaton vs slower Ca2+
2. Pacemaker has automaticity due to rising prepotential
3. Myocyte has a plateau phase
4. Lower resting potential
5. Faster conduction rate (1m/s vs 0.05)
How do autonomic factors alter the slope of the prepotential? 2007-1, 2003-1
Sympathetic:
- speeds Ih
- NA -> via 1 receptors -> cAMP -> opens L channels ->
increased ICa -> increases slope of prepotential -> increases
rate
Parasympathetic:
- Vagal cholinergic stimulation -> ACh release -> M2 receptors via
B subunit of G protein -> increased intracellular K+ -> slows Ih
and cAMP -> hyperepolarization/decreased slope -> slows rate
2010-2, 2005-1, 2003-2, 2003-1
List in order, the mechanical phases of the cardiac cycle
Please draw the pressure changes in the ventricle that occur during the cardiac cycle
1. Atrial systole
2. Ventricular isovolumetric contraction
3. Ventricular ejection
4. Ventricular isovolumetric relaxation
5. Ventricular filling
2009-1, 2005-1
Describe the pressure and volume changes at the onset of systole
Describe the pressure and volume changes at the onset of diastole
At the start of systole:
- Mitral and tricuspid valves close (first
heart sound)
- Ventricles start to contract
- AV valves bulge into atria (jugular c
wave)
- Isovolumetric contraction lasts 0.05s
- Until (L) > 80mmHg, (R) >10mmHg
- Then aortic and pulmonary valves open
At the start of diastole
- Ventricles relax
- Aortic and pulmonary valves close when
momentum of ejected blood overcome by
arterial pressure -> vibrations are second
heart sound
- Initially no change in volume: hence
isovolumetric relaxation
- AV valves open when pressure falls
below atrial pressures
Relate the aortic pressure to the phases of the cardiac cycle 2005-1
When do the heart sounds occur? 2003-2
2007-2
Draw and label a diagram of the jugular venous pressure wave
How does the ECG relate to the
jugular venous pressure
Explain the origins of the fluctuations of this wave
- a wave: atrial systole - some of the blood regurgitate
back into the great veins
- c wave: ventricular isovolumetric contraction tricuspid wave bulging
- x descent: ventricular ejection - atrial volume increase
as tricuspid pulled distally
- v wave: isovolumetric relaxation - rise in atrial
pressure prior to tricuspid valve opening
- y descent: ventricular filling - atrium empty when
tricuspid opens
2011-1, 2010-2, 2008-1, 2003-2 (+ contractility)
What are the parameters that define cardiac output?
CO = SV x HR
What are the factors that influence stroke volume?
1. Preload (= EDV or cardiac fiber length)
2. Afterload
3. Contractility
What is cardiac preload?
Amount of blood in ventricles at the end of diastole = end diastolic volume (Usually 130ml). Also the
amount of stretch of cardiac muscles c.f. resting length.
What factors affect preload?
- Blood volume
- Venous return e.g. increased by blood volume, venous constriction, muscle pump, negative
intrathoracic pressure, venous compression (uterus in pregnancy)
- Increased intrapericardial pressure, e.g. tamponade from pneumothorax, pericardial
effusion/hemorrhage, tumour, infection, IPPV
- Atrial contraction
- Decreased ventricular compliance, e.g. MI, infiltrates
How can cardiac output be measured?
1. Direct Fick method: amount of substance taken up/time = A-V difference x blood flow, so…
Cardiac Output
=
Amount of substance consumed (ml/min)
Aterial - Venous
-
commonly O2 is used: consumption measured by spirometry, and A-V difference across the lungs
from arterial vs pulmonary venous sample via catheter
2. Indicator dilution method: output of heart = amount of indicator divided by the average
concentration after a single circulation. Thermodilution with cold saline is a safe technique.
2011-2, 2009-1, 2008-1, 2006-2
What factors influence myocardial oxygen consumption?
1. Intramyocardial tension which is dependant on:
a) Pressure - after load, systolic pressure, contractility
b) Radius - preload (nb tension is proportional to radius as per law of Laplace)
c) Wall thickness
2. Contractile state of the heart i.e. ionotropy
As per Frank-Starling curve:
3. Heart rate i.e chronotropy
4. Also:
- cardiac work = SV x MAP of aorta for (L) and pulmonary a. for (R), note 7x more stroke work for
(L) ventricle b/c aorta MAP = 80mmHg c.f. pulmonary MAP 10mmHg)
- Pressure load increases O2 consumption more than volume load
How does decreasing a patient’s heart rate improve symptoms of angina?
1. Decreasing HR decreases O2 demands
2. Lower HR = longer diastole, thus at a slower heart rate there is more time for coronary
circulation which occurs in diastole
What effect does preload and afterload have 2009-1
- Both increase work. Cardiac work = SV x MAP
- Also, both increase intramyocardial tension
 Preload: Law of Laplace: radius proportional to wall tension
 Afterload: Increase in pressure increases tension
- As per Frank-Starling law and curve, increased preload (EDV) increases SV = more work
- Pressure load increases O2 consumption more than volume load, thus AS causes more
angina than AR. Reason not well understood
- Because afterload aorta > pulmonary (aorta MAP = 80mmHg c.f. pulmonary MAP 10mmHg), note
7x more stroke work for (L) ventricle c.f. (R)
What are the changes in cardiac function with exercise and how these mediated? 2006-2
1. Rate and stroke volume
2. Adrenaline and sympathetic discharge
3. Venous return
What are the physical laws involved?
1. Starling
2. Laplace Law: P = 2T/R
2011-1, 2010-2, 2009-2, 2006-1
Please draw the starling curve
What factors influence myocardial contractility?
Positively Inotropic:
- Sympathetic stimulation via nerves or
circulating catecholamines
- Drugs such as xanthines, glucagon,
cardiac glycosides, adrenergic agents
- Post-extrasystolic potentiation
- Increased heart rate (small effect)
- Increased myocardial mass (chronic)
Negatively Inotropic:
- Metabolic abnormalities: hypoxia,
acidaemia, hypercarbia
- Reduced sympathetic tone
- Blockade of circulating
catecholamines
- Pharamcologic depression (Ca
blockers, antiarrhythmics)
- Myocardial disease
- Increased parasympathetic tone
- Reduced intracellular calcium
- Hypothermia
- Heart failure (intrinsic depression)
Frank-Starling Law
aka Starlings law of the heart:
“energy of contraction is proportional to the
initial length of the muscle fibres”
i.e. length of fibres (preload) is proportional
to the end diastolic volume
The Frank-Starling curve demonstrates the
relationship between SV and EDV
How do changes in myocardial contractility alter the relationship between end diastolic
volume and stroke volume? 2011-1
Frank-Starling Curve:
- Increasing contractility moves the curve upwards and to the left
- Decreasing contractility moves the curve downwards and to the right
- More contractility = more is ejected by ventricles giving lower EDV and more SV
2011-2, 2010-1, 2006-1
Describe the factors that control blood flow to the myocardium
At rest heart extracts 70-80% of O2. More O2 consumption requires more blood.
a) Chemical factors -> vasodilation: Local factors control radius of blood vessels (overall flow and
regional flow). Low O2 is the main controlling factor. Hypoxia increases concentrations of CO2, H+,
K+ lactate, prostaglandins, adenine nucleotides, and adenosine.
b) Neurogenic factors -> controlling radius of blood vessels (overall flow and regional flow)
Parasympathetic nerves: vagal stimulation dilates coronaries
Sympathetic nerves: α -> vasoconstriction, β -> vasodilatation. However giving NA -> increased
HR/contractility via β -> increased O2 demand -> vasodilation. Giving β-blocker and NA ->
vasocontriction via α only. So coronary flow is preserved if systemic blood pressure falls -> NA
release
c) Pressure gradients
- Flow is dependant gradient between arteries and veins: thus reduced in CHF where systemic
venous pressure is high
- During systole ventricular muscle pressure limits flow, especially to subendocardium of the left
ventricle: in AS both high pressure and high O2 requirement -> high risk for myocardial ischaemia
d) Viscosity of the blood
2007-2
Describe the factors controlling blood flow through skeletal muscle during exercise
- Mainly local regulation
- Mainly via low O2 -> arterioles and precapillary sphincters open because smooth muscle cannot
maintain contraction in hypoxic conditions
- Local metabolites: low PO2, high PCO2, increased K+, adenosine, lactic acid
- Temperature rise -> vasodilation
What other circulatory changes occur in the body during exercise and why
- Increased cardiac output via sympathetic stimulation (increased rate and contractility)
- Sympathetic vasocontrictor nerves/adrenaline -> contraction of peripheral aterioles not in skeletal
muscle (coronary and cerebral systems spared)
- Depends if exercise is isometric (length doesn’t change) vs isotonic (force doesn’t change)
Isometric:
 Psychic stimuli act on medulla oblongata -> decreased vagal tone (and cardiac
sympathetic stimulation) -> increased heart rate
 Stoke volume unchanged
 Blood flow to muscle limited by steady muscle contraction -> compression of vessels
 Systolic and diastolic blood pressure rises (in seconds)
Isotonic:
 Similar prompt increase in heart rate
 Also increase in stroke volume
 Vasodilation in exercising muscles
 Thus diastolic BP the same or lower, and systolic only rises a small amount
- Increase venous return due to muscle pump and thoracic pump
- Also increased return because venoconstriction of capacitance vessels
The Circulation
2011-2, 2009-1, 2008-1, 2006-2, 2005-2
What factors determine cerebral blood flow?
1. Intracranial pressure
2. Local constriction and dilation of cerebral
arterioles
3. Mean arterial pressure at brain level
4. Viscosity of blood
5. Mean venous pressure at brain level
- Monro-Kellie doctrine
- Cushing reflex
- Local autoregulation
What is the Monro-Kellie Doctrine?
Volume of blood (75ml), CSF (75ml) and brain (1400g) in the cranium at any time remains relatively
constant (within a rigid structure).
What substances are important for brain metabolism 2008-1
1. Oxygen ~49ml/min = 20% body O2 consumption
2. Glucose (major energy source) ~77mg/min
3. Glutamate (converted to glutamine as detox mech NH3 i.e. ammonia) ~5.6mg/min
What is Cushing’s Reflex? 2006-2
Physiologic nervous response to raised ICP resulting in triad of widening pulse pressure, irregular
breathing and reduction of the heart rate.
Increased ICP > 33mmHg -> ↓ CBF -> ischaemia of RVML - ↑ systemic BP and heart rate (first
stage) –> stimulation of baroreceptors –> stimulation of vagal outflow –> bradycardia (second stage)
2010-1, 2009-1, 2003-2
Describe how tissues regulate their own blood flow
- 2 theories to autoregulation
Myogenic: Intrinsic contractile response of smooth muscle to stretch, so as blood pressure rises the
vessels walls are stretched and the vascular smooth muscle contracts. A greater degree of
contraction is seen at higher pressures. Respond to tension, so as per Law of Laplace the tension is
proportional to the radius (x distending pressure). To maintain a given wall tension at higher pressure
requires a reduction in the radius.
Metabolic: Products of metabolism are potent vasodilators and thus with reduced blood flow and
increased metabolism more accumulate. With increased blood flow more are washed away.
Vasodilators include: hypoxia, hypercapnea, acidosis, lactate, K+, temperature, histamine, adenosine
Describe how blood flow can vary in different parts of the brain 2005-2
- PET and fMRI show that there is marked variation in local blood flow with brain activity
- Active neurons attract blood flow
- Neurovascular coupling may adjust local perfusion in response to changes to brain activity
- Certain diseases show reduction in flow to affected areas (Alzheimers, Huntington, Manic
depressives, schizophrenia)
2004-2, 2003-2
Describe how blood flow is regulated at the level of the endothelium
Vasodilators:
1. Prostacyclin
- Endothelium derived from arachidonic acid via cyclooxegenase
- Inhibits platelet aggregation and vasodilates
2. Nitric oxide (EDRF)
- synthesized from arginine by NOS
- activated by agents that increase intracellular Ca2+ like bradykinin and acetylcholine
- activates guanylyl cyclase producing cGMP -> smooth muscle relaxation
- inactivated by haemoglobin
3. Carbon monoxide and H2S (hydrogen sulpide)
4. Kinins
Vasoconstrictors:
1. Thromboxane A2
- Platelet derived from arachidonic acid via cyclooxegenase
- Promotes platelet aggregation and vasoconstrics
2. Endothelin-1
- potent vasoconstricor
- resembles venom of Israeli burrowing asp
3. Serotonin
What other general effects do endothelins have on the cardiovascular system
- Positive inotrope and chronotrope
- Rise in ANP/renin/aldosterone
- Decreased GFR and renal blood flow
2010-1
Draw a diagram of the changes in systolic and
diastolic pressure as blood flows through the
systemic circulation
How does the total cross sectional area of the
vessels change through the systemic
circulation
2007-1, 2003-2
What is the normal value for venous return in the healthy human adult?
5 - 5.5 L/min
What are the major factors that influence venous return to the heart?
Right atrial pressure aka CVP
1. Circulating blood volume
2. Sympathetic and parasympathetic tone (venous capacitance)
3. Muscle pump
4. Thoracic pump (expiration creates higher negative pressure in thorax (from -2.5 to -6mmHg) and
also diaphragm creates some increased pressure in abdomen)
5. Effect of the heart pump (ventricular systole pulls tricuspid valve distally)
6. Gravity
What is the relationship between right atrial pressure and venous return?
-
venous return is determined by a pressure gradient (venous pressure – RAP) and venous
resistance
circulation is a closed system so cardiac output matches venous return (when averaged over
time)
achieves balance through Frank-Starling mechanism: if venous return is increased on lying down,
preload and SV increase leading to an increase in cardiac output
RAP = 4.6mmHg average, with range 2mmHg in inspiration to 6mmHg in expiration (Ganong)
2008-2, 2006-2, 2004-2
Where are Baroreceptors found in the body?
1. Stretch receptors in adventitia of vessel walls, major ones found in carotid sinus (ICA, rise or fall)
and aortic arch (apex, rise) to monitor arterial side of circulation.
2. Also low-pressure "cardiopulmonary receptors" in right and left atria, and pulmonary circulation to
monitor venous circulation
What is the effect of vessel wall distension on a baroreceptor?
- Stretch of vessel wall leads to increased baroreceptor discharge
- More sensitive to pulsatile pressure than constant pressure
- Transmitted by afferents in glossopharyngeal (carotid sinus nerve) and vagus (aortic depressor
nerve) nerves to medulla/vasomotor area
- NTS -> glutamate to CVLM -> GABA to RVLM: inhibits sympathetic vasoconstriction
- NTS -> dorsal motor nucleus and nucleus ambiguous: parasympathetic/vagus stimulation
Net effect is:
1. Inhibition of tonic discharge of sympathetic vasoconstrictor nerves
2. Excitation of cardiac vagal innervation
-> Results in vasodilation, with decrease in BP, HR and CO.
What is the effect of chronic hypertension on the activity of the arterial baroreceptors 2006-2
They ‘reset’ to maintain normal basal activity at the elevated blood pressure (reversible, unknown
mechanism)
What is the Set Point? 2004-2
- Neutral MAP for vasomotor centre, around 100 mm Hg
2007-1, 2003-2
What are the major factors affecting the regulation of arterial pressure?
1. Baroreceptor reflex
 rapid, adjusts for changes in posture
 aortic arch and carotid sinus
 messages via IX and X -> medulla (RVLM)
 autonomic nervous system to adjust HR/contractility (vagal) and peripheral vascular
resistance (sympathetic)
2. Renin-angiotensin system
 longer term adjustment of blood pressure
 compensation of volume loss or BP drop via vasoconstrictor angiotensin II
3. Aldosterone release
 steroid hormone released from the adrenal cortex in response to ATII or high potassium
 stimulates sodium retention and potassium excretion by kidneys
 sodium is main ion determining amount of fluid in vessels via osmosis, thus increases fluid
retention and indirectly BP
4. Caridiopulmonary and atrial stretch receptors
 feedback by regulating the secretion of ADH (vasopressin), rennin and aldosterone
 increase blood volume which increases cardiac output (by Frank-Starling law)
5. Peripheral chemoreceptor reflex
 In carotid and aortic bodies
 decreased flow in hypotension stimulates them
2005-1
Describe the cardiovascular compensations to acute blood loss.
Tachycardia; Vasoconstriction; Venoconstriction.
Describe the other physiologic compensations to acute blood loss.
- Tachypnoea and
Increased:
- Adrenaline/noradrenaline (sympathetic)
- Vasopressin
- Glucocorticoids
- Renin/angiotensin/aldosterone
- Erythropoietin
- Plasma protein synthesis
2008-1
What are the basic factors which determine the rate of flow of blood through a blood vessel?
Flow = Pressure/Resistance
Poiseulle-Hagen formula
Where:

= viscosity
L
= length of tube
r
= radius
What factors cause turbulent flow in a blood
vessel?
Loss of laminar flow, the probability of this can be expressed by Reynold’s number
Where:
ρ is the fluid density
D is the diameter of the tube
is the velocity of flow
viscosity of the fluid
V
η is the
The higher the value of Reynold’s number the greater the probability of turbulence, which usually
occurs when Reynold’s number is between 2000-3000.
2005-2
What factors cause turbulence in blood flow
-
“critical velocity”, density/viscosity, diameter
Reynolds number gives probabilty
Why is blood flow slower in capillaries
- highest total cross sectional area (4,500 cm2, i.e. 1000x that of the aorta)
- velocity = flow/area
What is the relationship between pressure and wall tension in blood vessels of different sizes
- As per Law of Laplace, P = T/r
- Smaller vessels have less tension to balance the pressure
What is the relationship between pressure and wall tension in the heart
- ventricular dilation means more tension required to generate the same pressure = more work