Section C: Cardiovascular Physiology

I: STRUCTURE & FUNCTION OF THE HEART

Describe the structure & functional significance of the conductive, excitatory & contractile elements of the
heart

Cardiac muscle is a syncytium in which cells are so tightly bound together that when one of them is excited APs
spread to all of them. Intercalated discs which form gap junctions separate the individual cells from one another.
This allows the atria or ventricles to contract as a single unit. The atrial syncytium is separated from the ventricular
syncytium by the fibrous tissue surrounding the valvular rings. The cardiac AP is conducted from the atrium to
ventricle through the atrivoventricular bundle.

II: ELECTRICAL PROPERTIES OF THE HEART

Explain the ionic basis of spontaneous electrical activity of cardiac muscle cells (automaticity)
AP of a pacemaker cell & AP of the SA node – ion fluxes
Pacemaker cells are rhythmically
discharging cells that have a
membrane potential that decline
after each impulse to the firing
level. At the peak of each
impulse IK brings about
repolarisation. IK then declines
 K+ efflux & the membrane
begins to depolarize (1st part of
prepotential). Ca2+ channels
open: 1st Transient channels
(completes prepotential) then
Long-lasting (produces impulse).

Prepotentials are normally only prominent in SA & AV nodes, however

“latent pacemakers” are present in other portions of the conduction system
that can take over if conduction blocked. Atrial & ventricular fibres only
discharge spontaneously when abnormal or injured.

Vagal stimulation  decrease of prepotential slope - due to K+ conductance & slowed opening of Ca channels.
Sympathetic stimulation  increased prepotential slope – due to  Transient Ca channel opening.
Describe the normal & abnormal processes of cardiac excitation
02A2 Draw a labelled diagram of a cardiac action potential highlighting the sequence of changes in
1995 ionic conductances. Explain the terms 'threshold', 'excitability', and 'irritability' with the aid of a 56%
diagram. AP of the ventricle/myocyte 10 – ion fluxes 6

Action potential - a wave of electrical discharge that travels along the membrane of an excitable cell. Cardiac APs
differ between different types of cardiac cell e.g. APs in the SA node area (slow response) are different to the
ventricles (fast response).

Phase 0 – Rapid depolarization - 2

Na+ influx (peak may reach +40mV).
Triggered by depolarization of
pacemaker cells. Chemical and
electrostatic forces both favour the entry
of Na+ into the cell through fast opening
voltage gated Na+ channels. K+
conductance is reduced because the
potassium inward rectifier channel
becomes non-conducting at positive
potentials. The peak of the action
potential may reach +40mV.

Phase 1 – Rapid partial

repolarisation - closure of fast voltage
gated Na+ channels, opening of rapidly
activating delayed rectifier K+ channels
(IKr)  K+ efflux, opening of Cl-
channels  Cl- influx. Chemical and
electrostatic forces both favour the
efflux of K+ to generate this early partial
repolarisation.

Phase 2 – Prolonged plateau - 2 Ca2+ influx (slower & more prolonged opening of voltage gated “L” Ca
channels) & continued K+ efflux.
Phase 3 – Final repolarisation - 2 K+ efflux - opening of slowly activating delayed rectifier K+ channels (IKs).
Chemical forces that favour K+ efflux predominate over electrostatic forces that favour its influx. Normalisation of
Na+ and Ca2+ permeability (closure of Ca2+ channels).

Phase 4 – Back to RMP –90mV - the chemical forces that favour K + efflux very slightly exceeds the electrostatic
forces that favour K+ influx.

 Threshold – the level of depolarization at which a self propogating AP is generated. This is determined by
the sensitivity of the ion channel responsible for depolarisation and the relative concentrations of the ion
being transported….
Ventricular muscle cell -65mV: depends on the voltage sensitivity of the fast sodium ion channel, and the
concentration of Na+ outside the cell.
SA node -40mV: threshold is reached by steady depolarisation of the resting membrane, rather than by a sudden
change in electrical potential. This allows the SA node to make its own beat (automaticity) and allows regular
pacemaker activity (rhythmicity).

Threshold intensity – the minimal stimulus required to produced an AP.

All or none law – an AP will fail to occur below the threshold intensity, and will always occur at the same form &
amplitude above the threshold regardless of the strength of the stimulus.
Absolute refractory period – the period from where firing level is reached until repolarisation is 1/3 complete.
During this period no stimulus will excite the nerve. This is much longer in cardiac than skeletal muscle.
Relative refractory period – period from where repolarisation is 1/3 complete until the start of after-depolarisation.
During this period a greater than normal stimulus will excite the nerve.

 Excitability - is the ease with which a myocardial cell can respond to a stimulus by depolarising. If a cell
can respond to a smaller stimulus than another cell, it is said to be more excitable. The degree of
excitablilty can be assessed by considering the size of the minimum stimulus necessary to depolarise the
cell and initiate an AP. The slope of phase 0 in the depolarisation is used as an index of excitability. The
more excitable the cell, the larger the slope and the higher the velocity of conduction. During the relative
refractory period excitability is reduced. Excitability (and consequently the slope of phase 0) increases
progressively as the stimulus occur later in the refractory period. When the resting membrane potential is
reached, full excitability is restored and the phase 0 slope returns to its steepest. Cardiac excitability
depends on activation, inactivation and recovery of various ion channels.

 Irritability – diminished potential between resting and threshold e.g. hyperkaelamia. As irritability
increases depolarisation is easier, but there is decreased gradient & conduction velocity of phase 0.
Immediately after the AP, the membrane is transiently hyper-excitable and is said to be in its vulnerable
period. During this time relatively weak stimuli in the form of delayed after depolarisations can propagate
APs, leading to extra beats or sustained arrhythmias.

Briefly discuss the interaction of the action potential duration and conduction velocity in the
1993  
ventricular myocardium and its effect on myocardial performance
With HR there is AP because AP occurs earlier in the inactivation period. This decreases duration of diastole >
systole. Results in decreased atrial + ventricular filling  heart failure. Results in decreased myocardial blood flow
 rate related ischaemia (worse in subendocardial area).

Explain the physiological basis of the ECG in normal & pathological states
See clinical measurement section

Factors that may influence cardiac electrical activity

Mechanical events of the cardiac cycle & correlate this with electrical & ionic events

Draw the cardiac cycle

THE CARDIAC CYCLE

= one complete sequence of ventricular systole & diastole

1. Atrial Systole - SA pacemaker initiates excitation, which spreads

across the atria  atrial contraction & pressure within both atria (a-
wave of the JVP)  additional ventricular filling.
Little blood is pumped in a retrograde direction due to the momentum of blood entering the atria & contraction of
the venous orifices. Atrial contraction is not necessary for ventricular filling (30%), however with HR when
diastole is abbreviated & disease states of the AV valves the atrial contribution may be important.

2. Isovolumetric Contraction Phase - excitation of the ventricles occurs as the wave of excitation passes through
the AV node, bundle of His and Purkinje system. Ventricular contraction starts within 10 msec  rapid
ventricular pressure.
Not true isometric contraction, as some fibers lengthen and others shorten as the ventricle changes shape. The
maximal rate of dP/dt ~ 1600 mmHg/sec (an indicator of the contractile state of the myocardium) = a rise in pressure
from near 0 to 80 mmHg in 1/20th second.
The rapid rise in ventricular pressure is transmitted across the semilunar valves and appears as a small rise in the
aortic pressure trace. When ventricular pressure exceeds aortic pressure the valves begin to open ending this phase.
NB: the minimum aortic pressure (diastolic), actually occurs in ventricular systole

3. Ventricular ejection
 Rapid Ejection Phase
Associated with an abrupt rise in ventricular and aortic pressures and a rapid flow of blood. Ventricular pressure
exceeds aortic due to the force required to accelerate the bolus of blood from the heart into the inductive load of the
aorta. Because of the high ventricular pressure, unless the papillary muscles perfectly compensate, the AV valves
bulge into the atria (c-wave of the JVP). Soon after this increase the atrial pressure falls due to the descent of the
base of the heart
and stretching of the atria (x descent of JVP). This aids the return of blood from the periphery.
Ventricular volume reduces slowly at first due to inertial forces but the increases in rate until the end of this phase.
Systolic arterial pressure may be used as an arbitrary demarcation point between the rapid and reduced ejection
phases. The peak in arterial pressure follows the peak in flow from the heart due to the distensibility of the aorta
which accumulates some of the outflow. This causes dampening and lagging of the pressure pattern.
  Reduced Ejection Phase
Both the contractile forces and pressure within the ventricles are decreasing during this phase & are less than those
within the aorta by several mmHg. Flow continues due to the momentum of the bolus of blood into the aorta.
Peripheral aortic run-off, however, exceeds inflow from the heart and pressure declines.
Repolarisation of the myocardium occurs during this phase. The mechanical and electrical events of the myocardium
are not synchronous and the fibers may be fully repolarised before the ventricles have reached a relaxed state.

Stroke volume ~ 80 mls

LVEDV ~ 120 ml
Ejection fraction ~ 2/3 (may increase to ~3/4 with massive SNS activity & is often less than 1/2 in disease)

The end of systole occurs at the beginning of the 2nd heart sound. The ventricular pressure is decreasing very rapidly
and there is reversal of flow toward the heart, closing the valves and generating the second HS. The sudden increase
in back-resistance to flow increases aortic pressure giving rise to the incisura or dicrotic notch. NB: this occurs only
in the aortic pressure trace, not the LV pressure trace.

4. Isovolumetric Relaxation Phase

Both valve sets are closed & ventricular pressure drops very rapidly. Atrial pressure is increasing to its maximum,
due to the movement of blood from the periphery & movement of the base of the heart back to its resting position
(v-wave of the JVP).

5. Ventricular Filling
 Rapid Filling Phase 60%
Ventricular pressure decreases below atrial, the A-V valves open and filling occurs rapidly. As the ventricle fills
intraventricular pressure increases slowing the rate of filling.

 Reduced Filling Phase 10% = diastasis

Only significant if the diastolic period is abnormally long, when flow may actually cease.

Synchrony of Contraction
LV is first to start contraction and the last to start to fill, the differences between the ventricles is only a few sec/100.
1. Excitation is initiated in the RA and rapidly conducted to the ventricles by the AV node
2. LV contraction starts first, with closure of the mitral valve occurring within ~ 30msec of Q-wave of the ECG.
3. RV contraction lags due to the anatomy of the conducting system by ~ 15msec
4. The pulmonary valve opens first (~ 60msec after Q-wave), and pulmonary flow begins 10 ms before aortic due
to the lower pressure in the pulmonary circuit.
5. The isovolumetric period is: LV ~ 40 ms, RV ~ 15 ms
6. Because of higher systemic pressure LV outflow ends first with the LVET being shorter that the RVET.
7. The mitral valve opens after the tricuspid due to the greater time for ventricular pressure to drop below atrial

Length of Systole & Diastole

Systole - the duration of systole is rate dependant & more fixed: 70 bpm ~ 0.3 sec, 200 bpm ~ 0.16 sec (50%).
Shortening with tachycardia is due mainly to a reduction in the duration of systolic ejection time.
Diastole - 70 bpm ~ 0.62 sec, 200 bpm ~ 0.14 sec (25%) – this is significant because…
1. LV subendocardial blood flow only occurs during diastole
2. Most of the ventricular filling occurs in diastole
3. Tetany cannot occur (like skeletal muscle) has a theoretical maximum of 400 bpm. However the AV node will
not conduct at > ~ 230 bpm

Heart sounds
1st – closure of AV valves @ commencement of systole – if the mitral & tricuspid valves don’t close simultaneously
 splitting
2nd – closure of aortic & pulmonary valves at end of ejection
Pressure traces - from R atrium to pulmonary artery

Pressure traces – JVP/CVP/RAP trace 10 *LAP trace is similar

The JVP gives an indication of right atrial pressure, as there are no valves between the internal jugular vein and right
atrium. Consists of 3 peaks (a, c & v waves) and 2 troughs (x & y descents).
a-wave (occurs immediately before carotid pulsation) - produced by atrial systole
c-wave – rise in atrial pressure by bulging of tricuspid valve into the atria during isovolumetric ventricular
contraction.
x-descent - occurs at the cessation of atrial contraction (in L atrium when aortic valve opens due to descent of
ventricles pulling down + lengthening the atria their capacity & dropping the pressure)
v-wave (occurs simultaneously to carotid pulsation) - develops due to venous return during systole (AV valves are
closed)
y-descent - occurs when the tricuspid valve opens

Causes of  JVP Causes of  JVP

- heart failure - haemorrhage
- tricuspid stenosis or regurgitation - other forms of hypovoleamia
- pericardial effusion or constrictive pericarditis
- cardiac tamponade
- renal disease  salt & water retention
- fluid overload - overtransfusion/excessive fluid intake
- superior vena caval obstruction (pulsation is absent)
- hepatomegaly
- hyperdynamic circulation

Large a-wave - caused by resistance to ventricular filling.

Cannon a-wave - occurs when the atrium contracts against a closed tricuspid valve e.g during complete heart block.
Large v-waves – occurs when right ventricular pressure is transmitted directly to the right atrium e.g TR

Determinants of CVP 4 ***see question below

Venous return from body – blood volume, posture, venous tone, intrathoracic pressure, intrapericardial pressure
Right ventricular filling – RV diastolic compliance, tricuspid disease, HR
Right ventricular emptying – contractility, pulmonary artery pressure
04B10 Draw and label a left atrial pressure trace against time. List the physiological factors which 19%
95A3 affect left atrial pressure and explain their effects. 2 68%  
Pressure traces - LAP

Normal L atrial pressure = 2mmHg (varies from 1-5mmHg). Usually measured indirectly as the pulmonary artery
wedge pressure and is an index of LV preload. Normally the same value as LVEDP

Factors affecting LAP

Venous Return – (from body  lungs left atria) influenced by…
1. Blood volume – volume  VR & LAP. volume  VR & LAP.
2. Posture – supine erect, blood pools in LL (300-800mls,  ~ 2L/min CO)   VR & vice versa.
3. Venous tone - veins are capacitance vessels & store 65% BV (erect). venous tone  VR & LAP.
venous tone  VR & LAP. Venous valves - directs blood towards heart, prevent pooling in LL 
increase VR. Incompetent valves  pooling of blood in LL veins.
4. Intrathoracic pressure - intrathoracic pressure e.g. IPPV  obstruction to filling of R heart  preload
& L atrial pressure. e.g. in IPPV and valsalva, transient  in LAP initially due to compression of
pulmonary vessels and  VR to LA  LAP. Also due to direct external compression of LA. However, this
is short-lived and LAP declines soon after it incline. Overall increase LAP
5. Intrapericardial pressure - intrapericardial pressure inhibits atrial filling preload  VR  LAP.
However direct pressure effect  LAP.
6. Obstruction to pulmonary flow  VR & L atrial pressure

Left ventricular filling – influenced by…

1. LV Diastolic compliance - compliance allows easier ventricular filling & LAP & vice versa
2. Mitral valve disease – mitral stenosis inhibits ventricular filling   LAP (both due to L atrial
hypertrophy &/or dilation). Mitral regurg  L atrial pressure from backflow.
3. HR - Effect of variation in heart rate. Tachycardia  diastolic filling time  ??LAP

Left ventricular empyting – influenced by…

1. Contractility - contractility in LV failure, LV unable to pump against a normal afterload  LVEDV and P
 LAP.
2. Afterload - afterload  artial outflow + L atrial pressure. afterload atrial ouflow + L atrial
pressure.

LV diastolic compliance
LV compliance = LVEDV
LVEDP
LAP = LVEDP = LVEDV
LV compliance
 LV diastolic compliance e.g. LV hypertrophy, initial IPPV/ phase I valsalva, impaired relaxation (ischaemia),
extrinsic compression (pericardial effusion, constrictive pericarditis)  LAP and vice versa

Left ventricular pressure waveform/time curve 7 = Wiggers diagram

R ventricle & pulmonary artery - same

curve as the L ventricle + aorta, however
the pressures are different: 20-25mmHg
pulmonary systolic (120mmHg) &
8mmHg pulmonary diastolic.
Radial artery waveform 4 – determinants & definitions of mean, systolic & diastolic pressures
Blood pressure - arises from the force of myocardial contraction acting on blood in the heart. The force gives rise to
tension & Laplaces law applies….Pressure = (2 x tension) / radius

Driving pressure in laminar flow is proportional to flow rate… P = KV

Ohms Law: Pressure = Flow x Resistance Resistance is driving pressure divided by flow
P = VR R = P/V

Mean blood pressure = cardiac output x peripheral resistance

Systolic Pressure: begins with opening of aortic valve. This reflects maximum left ventricular systolic pressure
exerted on the walls of the arteries during the contraction phase of the heart and may be termed the ascending limb.
Diastolic Pressure: relates to the level of vessel recoil or amount of vasoconstriction in the arterial system or the
lowest arterial blood pressure reached during any given ventricular cycle. May be termed the descending limb.
Pulse Pressure: difference between systolic and diastolic pressure.
Mean Arterial Pressure: average pressure in the arterial system during a complete cardiac cycle. Systole requires
one-third of the cardiac cycle, diastole normally during two-thirds. This timing relationship is reflected in the
equation for calculating MAP. MAP = SP + (2DP)/3 or MAP = DP + 1/3SP

Radial artery vs. aortic waveform 6 Aortic pressure trace 2

Dorsalis pedis pressure vs aortic waveform
Draw both aortic root and a radial artery pressure wave forms on the same axes. Explain the
99B8 50%
differences between them. Changes with aging
AORTIC
 Dicrotic notch (incisura) – with
ventricular pressure decrease (end systole)
reversal of blood flow towards the heart
occurs  closure of aortic & pulmonary
valves (second HS). The sudden increase in
back-resistance to flow increases aortic
pressure giving rise to the dicrotic notch.
 Anacrotic notch - reflected wave against
closed aortic valve during isovolumetric
contraction.

RADIAL - distorted shape related to reflection,

resonance, and damping occurring in the arterial tree
and different speed of transmission of different
pressure components (high pressure components
travel quicker).
 Delayed onset - because the time taken for
the pulse to reach the periphery.
 Steeper upstroke of radial - due to
decreased compliance.
 Greater amplitude & narrower wave 
higher systolic pressures because of
reflection and summation, tapering & faster transmission of pressure wave.
 Wider pulse pressure, although mean pressure (area under the curve) is similar despite the change in
shape.
 Diastolic hump - due to reflection and resonance.
 Loss of dicrotic/anacrotic notch - due to damping of high pressure components.

Elderly – both the ventricular & aortic compliance are reduced.

 Aortic wave form is similar to radial pulse wave form because the peripheral vessels are less compliant.
 Slower upstroke due to decrease myocardial performance.
 Higher peak pressure (L ventricle & aorta) during systole - decreased compliance of the aorta (loss of
elastic fibres and atherosclerosis)
 transmission velocities of the arterial pulse – because of stiffer aortic walls (decreased compliance)
 Slower HR – due to vagal tone
III: DETERMINANTS & CONTROL OF CARDIAC OUTPUT

A: Explain the Frank-Starling mechanism & its relationship to excitation contraction coupling
1993 Quote Starlings law of the heart. Outline the factors that determine the right ventricular
 
end diastolic volume

Frank-Starling law 7 – energy of contraction is proportional to the initial length

of the cardiac muscle fibre.

Length-tension relationship - Initial fibre length depends on end diastolic volume

& the pressure developed in the ventricles is proportionate to the total tension
developed. As the muscle is stretched the developed tension reaches a maximum,
then declines as the stretch becomes more extreme.
Sarcomere length  maximal tension = 2.2m

Frank Starling curve 2 – depicts the relationship between ventricular SV &

LVEDV.

As VR increases, CO
increases, so that VR always equals CO. Two mechanisms are responsible for this…
1. Heterometric regulation “Frank Starling Mechanism” - regulation of CO as a result of changes in cardiac
muscle fibre length.

preoload  force of contraction (Starlings law)  SV

SA node stretchHR

This is important in rapidly responding to acute changes in VR & keeping L&R ventricular outputs the same over
time.

2. Homeometric regulation - regulation in CO due to changes in contractility independent of muscle fibre length
resulting from changes that  intracellular Ca2+.
B+C: Define preload, afterload & myocardial contractility and factors that determine them
Myocardial performance – determined by HR, preload, afterload & contractility
The function of the heart is to pump blood to body tissues myocardial performance can be assessed by the volume
of blood pumped per unit time. CO = SV x HR SV is determined by preload, afterload & contractility
 the 4 factors that determine myocardial performance are HR, preload, afterload & contractility.

 Preload
Preload 5 – the load on myocardial muscles just prior to contraction. This load determines the length of myocardial
cells at the start of contraction  preload = initial fibre length.

Indices of preload – because fibre length cannot be determined other indices of preload are used…
1. LVEDV (left ventricular end diastolic volume) – because blood volume  length myocardial cells.
*measured with echocardiography

LVEDV is related to LVEDP (LVED pressure) by compliance of the ventricular wall:

LV compliance = LVEDV/LVEDP

2. LVEDP or LAP - LVEDP is the filling pressure of the LV & is almost the same as LAP. *difficult to
measure as require catheterization of the L heart.
PCWP or PAOP – can estimate L sided filling pressures from the R side of the circulation via a Swanganz catheter.
Relationship of PAOP to LV preload - correlates well with the LAP – principle is that occlusion stops flow
through that vessel, so there will be no pressure drop along the length of the vessel (at same horizontal level) the
pressure measured at the tip of the catheter will be the same as the downstream site where flow first occurs due to
joining with other vessels.
LAP does not correlate with LVEDP in some circumstances e.g. MS

Pressure traces - pulmonary artery pressure 4, PA occluded pressure 3, PCWP

Determinants of pulmonary artery wedge pressure 2

Determinants of LVEDV

Factors affecting preload…

Venous return from atria to ventricle (filling) – atrial contractions, blood volume, posture, venous
tone/skeletal muscle pumping, intrathoracic pressure (IPPV  filling), intrapericardial pressure (tamponade 
filling), with standing
LV Compliance -  ventricular compliance  preload,
External pressure – IPPV + tamponade  filling
AV valve disease - incompetence/stenosis  preload
?HR

3. RAP & CVP – can be used as indices of filling pressure + preload of the R heart. *measured with CVP
line + water manometer.
  Afterload

Afterload 7 – The impedence to the ejection of blood from the heart into the arterial circulation i.e. the pressure
against which the ventricle must contract.

Indices of afterload
1. Mean arterial pressure – during systole, because that is when blood is being ejected
2. End systolic pressure

Factors affecting afterload…

Aortic valve e.g. aortic stenosis increases afterload +++
Systemic vascular resistance – 60-80% of afterload
Impedence – elastic = kinetic
Other – emboli, clamps, fistula

 Myocardial contractility
Myocardial contractility 15 - is the factor that is responsible for changes in myocardial performance which are not
due to changes in heart rate, preload or afterload.
Myocardial work - contractility is the amount of work that the heart can perform at a given load (if HR is constant).

Myocardial contractility exerts a major influence on SV.

The intracellular mechanism associated with contractility is raised intracellular Ca2+.

Indices of myocardial contractility - estimation/measurement of myocardial contractility 2

(dp/dt)max – the maximum rate of change in pressure of the L ventricle during isovolumetric contraction can
estimate contractility. A more forceful contraction is associated with a greater rise of pressure.
***Not useful clinically because does not take into account changes in preload + afterload and requires
catheterization of the L side of the heart  invasive +++.

Increased
Sympathetic stimulation or NA or A
HR & ventricular extrasysytoles (Ca2+)
Catecholamines – via 1  adenylate cyclase 
cAMP
Caffiene/theophylline – inhibit breakdown of
cAMP
Glucagon - cAMP formation
Digitalis
Calcium

Decreased
Parasympathetic nerve stimulation
Hypercapnia
Hypoxia
Acidosis
Drugs – barbiturates, etc
Cardiac failure
D: Describe myocardial oxygen supply & demand & the conditions that may alter each
Determinants of myocardial O2 supply & demand 5
Myocardial O2 balance 3

Heart O2 demand – depends on myocardial wall tension, contractility & HR. Also basal energy metabolism,
external work & energy for electrical activation.

Cardiac O2 consumption is about 7-9mL/100g/min at rest or 80% of the O 2 delivered to it. Cardiac venous O2
tension is low & little extra can be extracted from the coronaries increases in O2 consumption requires  coronary
blood flow. Ventricular work = SV x MAP (either aorta or pulmonary artery) and correlates with O 2 consumption.
L ventricle is doing x7 more stroke work. Pressure work produces a greater O2 consumption than volume work
e.g. angina occurs more frequently in aortic stenosis (pressure) than in aortic regurg (volume). Sympathetic
stimulation  HR & contractility  O2 consumption. However this is slightly offset by end systolic volume &
radius  O2 consumption.

Supply = Coronary blood flow x CaO2

= (CPP/CVR) x CaO2

Coronary perfusion pressure = aortic diastolic pressure – larger of LVDP or RAP

Also depends on HR – with HR there is less time for perfusion of blood during diastole to the subendocardial area
ischaemia is more likely here.
E: Describe Guyton’s CO curves & explain factors that affect them
Cardiac function (CO) curves 4

Cardiac function curves – show effect of change in RAP on CO. The

plateau of the normal CO curve is 13L/min. This means the normal
heart can without any stimulation pump VR up to x2.5 normal
without the heart limiting CO.

Hypereffective hearts – factors which the hearts pumping ability…

1. Nervous stimulation – SNS stimulation or PNS inhibition –
increase HR & contractility. Can 25L/min.
2. Hypertrophy – due to long term increased workload e.g.
marathon runners can increase mass by 50-75%, it is not
detrimental unless the load is so great that it damages the
heart.

Hypoeffective hearts – factors which the hearts pumping ability…

1. Inhibition of nervous excitation
2. Pathology – IHD, CAD, dysrhythmias, valvular heart
disease, congenital heart disease, myocarditis, cardiac
hypoxia.

Effects of external pressure on CO curves

The normal intrapleural pressure is –4mmHg. A rise in
intrapleural pressure to –2mmHg causes the curve to shift to the
right because to fill the cardiac chambers requires an extra
2mmHg RAP to overcome the increased external pressure on the
heart.
Factors that alter intrepleural pressure…
1. Respiration - 2mmHg during normal breathing
2. Breathing against a negative pressure – shifts to left
3. Breathing against a positive pressure – shifts to right
4. Opening the thoracic cage – increases intrapleural
pressure to 0mmHg shifts to right
5. Cardiac tamponade – shifts to right

Combinations of CO curves
F: Describe & explain vascular function curves & correlate these with CO curves
Vascular function (VR) curves 5
Factors that effect VR are… VR = MSFP – RAP / venous resistance
1. RAP – exerts a backward force on the veins to impede flow into the R atrium
2. MSFP - 7mmHg – degree of filling of the systemic circulation that forces blood back to the heart or
‘tightness’ of the systemic circulation (the pressure which would be measured in the systemic circulation at
complete circulatory arrest when the arterial & venous pressures equilibriate).
MSFP alters with sympathetic stimulation (constricts vessels, decreasing its capacity  25mmHg)
or inhibition (dilates vessels, increasing capacity  4mmHg).
MSFP alters with blood volume
– 4000ml = 0mmHg unstressed volume
– 5000ml = 7mmHg normal volume
– Rises with volumes because the extra blood stretches the walls of the vasculature

3. Venous resistance – normally 1.4mmHg/L blood flow.

These can be expressed by venous return curves – show effect of change of RAP on VR

As the hearts pumping ability

decreases the RAP rises which
decreases VR. If all nervous
circulatory reflexes are
stopped then when the RAP
reaches MSFP VR stops.
The plateau at negative atrial pressures is because as RAP falls below its normal of 0mmHg the negative pressure
causes collapse of the veins entering the chest.

Changes to MSFP
The greater the system is filled the easier for blood to flow into the
heart.
MSFP  shift upwards & rightwards
MSFP  shift downwards & leftwards

Changes to resistance to venous return

2/3 venous + 1/3 arterial (because capacitance is 1/30 smaller,
pressure increases dramatically & overcomes much resistance).
If resistance is halved, flow doubles and vice versa.

Combinations of VR curves
Guyton’s curves 3 – their application e.g. haemorrhage
Simultaneous CO & VR curves
In the complete circulation the heart & systemic circulation function together. This means the RAP is the same &
the VR = CO.

Point A – where VR = CO on the normal CO & VR curves. This is the equilibrium point.
G: Describe the pressure-volume relationships of the ventricles and their clinical applications
02B9 Draw a pressure volume loop for a left ventricle in a normal adult. Outline the information 67%
1996 that can be obtained from such a loop. 2 65%
Left ventricular pressure-volume loop 16 For L&R ventricle 2
Pressure-volume loops are generated by plotting simultaneous points of the left ventricular volume curve and the left
ventricular pressure curve.

Information to be obtained from the loop…

 Points on the loop
1 – Mitral valve closes
2 – Aortic valve opens
3 – Aortic valve closes (end-systolic point)
4 – Mitral valve opens

 Phases of the cardiac cycle

1 – 2: isovolumetric contraction
2 – 3: ejection
3 – 4: isovolumetric ventricular relaxation
4 – 1: ventricular filling

 LVEDV - maximal volume achieved at the end of

filling. It is the best estimate of preload (as the
EDV is the best estimate of preload in the heart).

 LVESV - minimal volume (i.e. residual volume) of the ventricle found at the end of ejection.

 SV - the width of the loop represents the difference between EDV and ESV, which is by definition the
stroke volume.  SV = EDV - ESV

 Ejection fraction can be calculated …. At rest usually 55-65%

Ejection fraction = (EDV – ESV) / EDV
= SV / EDV
= (120 – 50) / 120
= 0.58 or 58 %

 Afterload - the best index of afterload is the slope of the straight line connecting the LVEDV on the x-axis
with the end-systolic point on the loop or equivalently the angle this makes with x-axis (larger angle =
larger afterload, smaller angle = smaller afterload).

 Elastance - the filling phase moves along the end-diastolic pressure-volume relationship (EDPVR), or
passive filling curve for the ventricle. The slope of the EDPVR is the reciprocal of ventricular compliance
(i.e. equals the elastance or ventricular “stiffness”). This relationship is a curve rather than a straight line as
the elastance increases as the left ventricular volume increases.
LV elastance = LVEDP/LVEDV i.e. inverse of compliance “distensibility”
LV compliance = LVEDV/LVEDP
Diastolic ventricular compliance
Significance – the ventricle is easy to fill to 130mL but over this volume it is hard to overfill.

 Contractility - the maximal pressure that can be developed by the ventricle at any given left ventricular
volume is the end-systolic pressure-volume relationship (ESPVR) = the slope of the ESPV line which
represents the contracility of the ventricle.

 Stroke Work - The area inside the loop represents the external work performed by the left ventricle for
that cardiac cycle (stroke work).
Any given area on the pressure-volume loop represent work (pressure x volume = work).
Pressure-volume loops are poor ar estimating cardiac work because they fail to take into account HR
(which effects myocardial oxygen consumption, which in turn is proportional to cardiac work) and they fail
to account for changes in resting wall tension, which may also alter oxygen use.
External work, diastolic work, potential energy of the ventricle

 Increased Preload Increased Afterload

 Increased Contractility
H: Integrate the factors that determine CO
1990 Discuss the relationship between cardiac output and venous return. Include factors that
 
determine the magnitude of both.

Venous return – effects of RAP on VR, determinants of

Venous return is the quantity of blood flowing from the veins into the R atrium each minute.
VR = MSFP – RAP / venous resistance MSFP 7mmHg

Factors affecting Venous return/CVP (must affect MSP, RAP or venous resistance)
1. Muscle pump/valves
2. Intrathoracic pressure - intrathoracic pressure e.g. IPPV  VR & L atrial pressure.
Respiration - inhalation  negative thoracic pressure which VR  CVP
exhalation  CVP
diaphragmatic compression of abdominal organs   blood flow
3. Intrapericardial pressure – impedes atrial filling
4. Venous tone - venous tone  VR & L atrial pressure. venous tone  VR & L atrial pressure.
5. Atrial contribution to ventricular filling
6. Blood volume – volume  VR & L atrial pressure. volume  VR & L atrial pressure.
7. Posture - Gravity - head, feet. Supine  erect position causes pooling of blood in venous capacitance
vessels & VR.

Cardiac output is the quantity of blood pumped into the aorta each minute by the heart = SV x HR

Cardiac output 2 - determinants of 8

CO varies with level of activity… rest  5L/min
1. BMR
2. Execise – can 25-30L/min
3. Age
4. Size of body – CO increases proportionately with SA of the body. Cardiac Index – the CO per square meter
of body surface area 3L/min/m2

The primary controller of CO is VR, because as more blood returns the Frank-Starling mechanism allows the
heart to pump more blood due to increased stretch. whatever blood flows into the heart is automatically pumped
out of the heart.
Also as the heart is stretched the heart beats faster due to stretch on the sinus node & the Bainbridge reflex (as the R
atrium is stretched nervous impulse  vasomotor center  heart via sympathetic + vagal nerves HR).
In disease if the VR is more than the heart can pump, then the heart becomes the limiting factor that determines CO.

The VR is the sum of all the local blood flows through all the different tissues of the body. Tissue blood flow is
determined by autoregulation or the metabolic need of the tissue. The blood flow is changed by variations in
arteriolar tone. As flow increases there is an increased tendency to VR or as peripheral resistance decreases there is
an increase in CO.

Primary changes in HR or SV will not change CO unless there is increased demand for tissue blood flow. With HR
but no VR the extrathoracic veins draining into the heart collapse (because venous pressure falls below
atmospheric pressure)  SV & stable CO.
At extremes of HR <40 & >180 the ability of the heart to adjust SV to maintain constant CO is exceeded CO falls
& venous pressure occurs (low HR) or inadequate ventricular filling compromises SV (high HR).
IV: THE PERIPHERAL VASCULAR SYSTEM
A: Distribution of blood volume & flow in regional circulations and the factors that may redistribute blood

Aorta & other large artieries –

contains more elastic tissue,
which is stretched during systole
& recoils during diastole
“windkessel effect” 
continuous, but pulsatile forward
flow.

Arterioles – contains more

smooth muscle. They are
resistance vessels - small
caliber changes cause large
changes in total peripheral
resistance.

Capillaries – when precapillary sphincters are dilated the diameter is just sufficient to allow RBC to squeeze
through. In muscle junctions between endothelial cells permit passage of molecules up to 10nm. In brain they are
tighter & only permit very small molecules through. In most endocrine glands, intestine & kidneys junctions are
fenestrated (20-100nm) allowing large molecules through. Pericytes (wrap around endothelial cells) are involved
with synthesis of BM & extracellular matrix and regulation of flow through
endothelial junctions.

Veins – contain little smooth muscle, but considerable vasoconstriction can

occur & is important in circulatory adjustment. They are capacitance
vessels – act as a blood reserviour. Normally partially collapsed & can
accommodate a large amount of blood before pressure rises. Limb veins
contain valves (small, great, brain & visceral veins do not). Venule pressure
is 12-18mmHg, great veins outside the thorax 5.5mmHg & the CVP =
4.6mmHg
Thoracic pump – during inspiration the intrapleural pressure falls
from –2.5 to -6mmHg. CVP fluctuates from 6mmHg in expiration
to 2mmHg in inspiration. The drop in venous pressure in inspiration
assists venous return. Also the descending diaphragm compressed
intra-abdominal organs, also assisting venous return.

1994 Briefly discuss the factors that influence the rate of blood flow through a capillary bed  

B: Factors that determine the systemic

blood pressure & its regulation

Blood pressure 2

Blood pressure - arises from the force of

myocardial contraction acting on blood in the
heart. The force gives rise to tension &
Laplaces law applies….Pressure = (2 x
tension) / radius

Driving pressure in laminar flow is proportional to flow rate… P = KV

Ohms Law: Pressure = Flow x Resistance Resistance is driving pressure divided by flow
P = VR R = P/V

MAP = CO x SVR

Determinants of blood pressure Arterial pressure can vary with changes in CO (HR x SV) & SVR
Vasomotor control
Sympathetic nerves constrict arteries & veins and HR + SV discharge in a tonic fashion. BP is adjusted by varying
their rate of discharge.

The vasomotor centre – a group of neurons in the medulla are the main controllers of BP & HR. The neurons
cell bodies are located in the RVLM and they project to…
1. Sympathetic preganglionic neurons in the intermediolateral gray column of the spinal cord. The
neurotransmitter they release is glutamate.
2. Parasympathetic vagal fibres arising from the
dorsal motor nucleus of the vagus & the nucleus
ambiguous.
vasoconstrictor discharge  arteriolar constriction &
BP. Venoconstriction usually occurs, but changes in
capacitance veseels do not always accompany changes in
resistance vessels.

Factors affecting activity of vasomotor area

 Direct stimulation - CO2 & Hypoxia  Cushing reflex
 Excitatory inputs from…
Cortex via hypothalamus e.g. anger, sexual excitement
Pain pathways – afferents from the reticular formation (prologed
severe pain  vasodilation & fainting)
Muscles – afferents project to C1 neurons in RVLM. Pressor response
to stimulation of somatic afferent nerves is the somatosympathetic
reflex.
Carotid & aortic chemoreceptors
 Inhibitory inputs from…
Cortex via hypothalamus
Lungs – vagal afferents from the lungs  vasodilation & BP
Carotid, aortic & cardiopulmonary baroreceptors

Factors affecting stroke volume 2

Stroke volume – determined by preload, afterload & contractility
Neural input: sympathetic stimuli  contractility & SV and
parasympathetic stimuli contractility & SV

Heart rate – controlled mainly by parasympathetic (rate) & sympathetic

(rate) innervation = chronotropic action.
Cholinergic vagal fibres have more discharge at rest than the sympathetic
nerves. Atropine which blocks the vagal nerves increases the resting heart
rate from 70 to 150-180/min, because the sympathetic tone is unopposed. If both the noradrenergic & cholinergic
systems are blocked the heart rate is 100/min.
Interactions between components that regulate CO & arterial pressure

Effects of
various things on CO

C: Describe total peripheral resistance & factors that affect it

Total peripheral resistance/SVR 2– factors affecting

SVR – the resistance against which the heart pumps.

SVR (dyne s/cm5) = MAP – CVP(mmHg) x 80 (correction factor)

CO(l/min)

Determinants of SVR – predominantly by diameter of arterioles

 Local factors
1. Myogenic autoregulation
2. Metabolic autoregulation

 Substances produced by endothelium

1. NO
2. Prostacyclin
3. Endothelin

 Neural control
1. -adrenergic receptors – noradrenergic vasoconstrictor
fibres – have some tonic activity sympathectomy 
vasodilation.
2. 2-adrenergic receptors – vasodilation to muscle & viscera
3. Dopamine receptors – vasodilation to renal & splanchnic
vessels
4. SNS cholinergic receptors – vasodilation to skeletal muscle

Vasodilator fibres – have no tonic discharge. Vasodilation is produced

by tonic discharge of vasoconstrictor nerves. However in skeletal
muscle it can be produced by activating the SNS vasodilator system.

 Ciculating substances
1. Adrenaline
2. NA
3. Angiotensin II
4. ADH
5. ANP
6. Toxins/Histamine
7. Neuropeptide Y (NA postganglionic sympathetic nerves) - vasoconstriction
8. VIP (cholinergic nerves) – vasodilation
9. Substance P & CGRP (sensory nerves near blood vessels ) - vasodilation
D: Mechanisms involved in local vascular control & autoregulation

04A10 Describe the substances released by the endothelium. Explain the role they play in regulating 65%
01A6 blood flow through the peripheral circulation. 72%
Functions of vascular endothelium

Substances released by the endothelium

1. NO (endothelium derived relaxing factor)  vasodilation.
Synthesis - from arginine in a reaction catalyzed by nitric oxide synthase.
Release – shear stress, ACh, bradykinins, cytokines, ADP, serotonin, histamine & substance P.
Isoforms: NOS 1 – CNS, NOS 2 – macrophages + other immune cells, NOS 3 - endothelial cells.
Mechanism - diffuses to smooth muscle & stimulates guanylate cyclase to produce cGMP  vascular smooth
muscle relaxation (prevents Ca2+ influx). Is co-released when many factors act on the endothelium to allow large
arteries to also dilate & to help keep blood vessels with intact epithelium patent (when damaged areas are producing
substances  vasoconstriction)

2. Prostoglandins: Prostocyclin (PGI2)  vasodilation, inhibition of

platelet adherence to the endothelium + aggregation (prevents
intravascular clotting) & vascular permiability
Synthesis - COX-I converts arachidonic acid into prostaglandin precursors
Release – shear stress caused by pulsatile blood flow
Mechanism – Vasodilatation mediated by intracellular cAMP

3. Endothelins – family of 3 21aa polypeptides. Endothelin-1  very potent vasoconstriction (100x NA)
Synthesis – prohormone that is converted in endothelial cells by endothelin converting enzyme
Release - ET1 production stimulated by AII, catecholamnes,GH, hypoxia, insulin, shear stress, thrombin, HDL +
oxidised LDL.
Inhihibited by - NO, ANP, PGE2, PGI2 (prostacylcin).
Mechanism – Predominantly paracrine, though some is released into the blood stream.
ETa receptor (specific for endothelin-1) works via G protein + PLC  vasoconstriction.
ETb receptor (responds to all 3 endothelins) coupled to Gi  vasodilation.
Endothelin 1 – brain, kidney and endothelial cells
Endothelin 2 – kidneys, intestine
Endothelin 3 – blood, brain
Effects: POTENT Vasoconstrictor, renal vasoconstriction  GFR + Na reabsorption, ionotropic + chronotropic,
release of ANP, renin, aldosterone + catecholamines, modulates synaptic transmission, bronchoconstriction,
enhances gluconeogenesis & stimulates cell growth in numerous cell lines.

Factors effecting coagulation & fibrinolysis – not released, but expressed on surface of endothelium
Plasmin is a protease which lyses fibrin, thus dissolving clots and restoring regional circulation previously
interrupted by fibrin cross-linking and clot formation. Plasmin is the activated form of plasminogen, by the action of
tPA (tissue plasminogen activator) which is expressed (among other places) on the endothelial cell surface.

Tissue metabolites
ADP, H+ ions, adenosine, CO2 released from tissues ( endothelium not primary source) and diffusing into
regional circulations. Have been shown to increase regional blood flow via vasodilation, improving tissue
oxygenation and the removal of wastes and metabolites. Very important in skeletal muscle, brain and heart.

Role in regulation of blood flow through the peripheral circulation

Vasoactive regulators helping match regional perfusion to metabolic demand
Many vasoactive substances e.g. thromboxane A2, bradykinin, histamine & serotonin do no primarily arise from
endothelial cells.

Thromboxanes – thromboxane A2 (from platelets)  vasoconstriction & platelet aggregation

E: Mechanisms involved in maintaining blood flow to individual organs in the presence of changed perfusion
pressure (autoregulation)

1994 Describe the relationship between vascular tone and tissue oxygenation  

Autoregulation of blood flow 6

Autoregulation = the capacity of tissues to regulate their own blood flow. Most vascular beds compensate for
changes in perfusion pressure by changing vascular resistance so blood flow remains constant. All tissues except the
uterine vascular bed in pregnancy & portal supply of the liver are autoregulated.

1. Metabolic autoregulation – is the ability of a tissue to adjust its blood supply so that it receives sufficient flow to
carry out its functions. Due to locally released vasodilatory metabolite which accumulate in active tissues  vessels
dilation  blood flow  washing away of vasodilatory substances. Important for moment to moment regulation
of regional CBF.
Metabolic Theory: Vasodilator metabolites  relaxation of arterioles & precapillary sphincters. When blood flow
increases vasoactive substances are washed away.
P PCO2 tension - most pronounced in the skin & brain
O PO2 tension
O osmolality
H hydrogen or pH Histamine – in injured tissues

T temperature - fever & due to the heat of metabolism in active tissues

A adenosine
L lactate
K potassium– especially in skeletal muscle

Local vasoconstriction - injured vessels constrict strongly due to liberation of serotonin from platelets.

2. Pressure autoregulation – Myogenic theory of autoregulation – as pressure rises, stretch on vessel walls
increases & vascular smooth muscle responds by contracting (Law of Laplace) tone  radius + resistance 
return to normal blood flow despite increased pressure. Occurs within seconds.
F: Essential features of the microcirculation including fluid exchange (Starling forces) & control mechanisms
present in the pre + post-capillary sphincters
Microcirculation – refers to the smallest blood vessels in the body – smallest arterioles, metarterioles, precapillary
sphincters, capillaries & small venules.
1. Arterioles – contain smooth muscle & are major sits of SVR.
2. Capillaries – in many tissues e.g. skeletal muscle, remain closed with low flow for long periods are a
reserve when additional flow is required: vasodilator metabolites & sympathetic vasoconstrictor nerve
stimulation  dilation of precapillary sphincters  raised intracapillary pressure which overcomes the
critical closing pressure  blood flow
Vasomotion – intermittent flow in capillaries caused by precapillary sphincter contraction & relaxation.
3. AV shunts – some tissues e.g. skin contain AV shunts which are under nervous control for heat regulation.

Exchange of substances is major function – the microcirculation contains 5% of blood volume & is the site where
intravascular fluid contacts ISF. Exchange of water, electrolytes, gases, wastes, nutrients & heat occurs – this is
critical for survival. Substances pass through endothelial cell junctions, through fenestrations, via vesicular transport
or through cytoplasm (if lipid soluble). Transport across the capillary wall occurs by diffusion (quantatively more
important) or filtration.
1. Water – crosses by diffusion + filtration – through pores & gaps between endothelial cells
2. Electrolytes - diffusion through pores & gaps between endothelial cells
3. Lipid soluble substances + O2 + CO2 – easily diffuse through thin walls of endothelial cells
4. Proteins - pinocytosis

Diffusion Filtration
Volumes Large  80000L/day Smaller
Direction Biodirectional along whole capillary Inwards or outwards at any particular point
Net movement Goverened by concentration gradient – Ultrafilatration 20mL/min  18mL
usually no water concentration difference so reabsorbed + 2mL lymph (2-3L/day)
net = O Imbalance of hydrostatic & oncotic pressures
Substances Gases, nutrients & wastes Water

Give an account of the Starling forces within the capillary circulation.

1991  
Include specific reference to the pulmonary and glomerular capillaries.

Capillary fluid exchange 3 - Starling Forces 6 **See fluid section

A significant amount of fluid leaves the systemic capillaries as 'ultrafiltrate' - the water and electrolyte component of
plasma without protein (too large to be filtered across capillary endothelium).
Interstitial fluid volume depends on capillary pressure, interstitial fluid pressure, oncotic pressure, capillary filtration
co-efficient, number of active capillaries, lymph flow and ECF volume.

Filtration rate across a capillary depends on a balance of Starling forces…

1. Hydrostatic pressure gradient = capillary hydrostatic pressure (blood pressure) – interstitial fluid
hydrostatic pressure (the interstitial fluid varies from organ to organ). Interstitial pressure is usually
subatmospheric due to removal of fluid by lymphatics. Minimal lymph flow with interstitial pressure < -6
mmHg. Large increase (x20) between -6 - 0 mmHg, then plateaus and ceases to rise further @1-2 mmHg.

2. Osmotic pressure gradient = plasma colloid osmotic pressure – interstitial fluid colloid osmotic pressure.
The interstitial fluid colloid osmotic pressure is usually negligible so the osmotic pressure gradient =
oncotic pressure. Colloid oncotic pressure is that part of osmotic pressure (pressure due to particle
concentration) which is due to non-diffusible 'colloid' particles, usually proteins e.g. albumin.

…and 2 additional factors…

3. Reflection coefficient
The reflection coefficient can be thought of as a correction factor which is applied to the measured oncotic pressure
gradient across the capillary wall. The small leakage of proteins across the capillary membrane has two important
effects:
1. The interstitial fluid oncotic pressure is higher then it would otherwise be.
 2. Not all of the protein present is effective in retaining water so the effective capillary oncotic pressure is
lower than the measured oncotic pressure (in the same way that there is a difference between osmolality
and tonicity).
Both these effects decrease the oncotic pressure gradient. The interstitial oncotic pressure is accounted for as its
value is included in the calculation of the gradient.
The reflection coefficient is used to correct the magnitude of the measured gradient to take account of the ‘effective
oncotic pressure’. It can have a value from 0 to 1.
E.g. CSF & glomerular filtrate have very low protein concentrations and the reflection coefficient for protein in
these capillaries is close to 1. Proteins cross the walls of the hepatic sinusoids relatively easily and the protein
concentration of hepatic lymph is very high. The reflection coefficient for protein in the sinusoids is low. The
reflection coefficient in the pulmonary capillaries is intermediate in value: about 0.5.

4. Filtration coefficient
The net fluid flux (due to filtration) across the capillary wall is proportional to the net driving pressure. The filtration
coefficient (Kf) is the constant of proportionality in the flux equation which is known as the Starling’s equation.

The filtration coefficient consists of two components as the net fluid flux is dependent on:
1. The area of the capillary walls where the transfer occurs
2. The permeability of the capillary wall to water. (This permeability factor is usually considered in terms of
the ‘hydraulic conductivity’ of the wall.)
The filtration coefficient is the product of these two components: Kf = Area x Hydraulic conductivity
A ‘leaky’ capillary (e.g. due to histamine) would have a high filtration coefficient. The glomerular capillaries are
naturally very leaky as this is necessary for their function; they have a high filtration coefficient.

Filtration pressure = Kf.((Pc-Pi) - r.(Oc-Oi))

Kf – capillary filtration coefficient

R – reflection coefficient (represens the capillaries permeability to colloid particles)
Pc – capillary hydrostatic pressure
Pi - interstitial hydrostatic pressure
Oc – capillary oncotic pressure
Oi - interstitial oncotic pressure

Starling forces in various capillary beds - different capillary beds are subject to different Starling forces and
reflection coefficients.
1. Normal e.g. Muscle
Typical values  net driving pressures of 11 mmHg proximally (net
movement of fluid into the interstitium) and -4 mmHg distally (net
movement into capillary).
Capillary hydrostatic pressures - 25mmHg (arteriolar end) &
10mmHg (venous end).
Interstital hydrostatic pressures – 6mmHg (same along capillary)
Capillary oncotic pressure – 25mmHg (same along capillary)
Interstital oncotic pressure – 5mmHg (same along capillary)

Pulse pressure is 5mmHg (arteriolar end) & zero (venous end).

Blood moves slowly (usually 1-2sec) because of the large total cross
sectional area.

Capillary pressure is altered by the arteriole venous tone. Increased

arteriole constriction reduces the driving pressure into the interstitium.
Increased venous pressure increases capillary hydrostatic pressure and
promotes the flow of fluid into the interstitium. Usually fluid moves
into the interstitial space at the arteriolar end of the capillary, where
filtration pressure across its wall exceeds oncotic pressure, and into the capillary at the venule end, where oncotic
pressure exceeds the filtration pressure.
2. Renal Glomeruli - the GFR is 180L/day
High filtration coefficient (water permeability)
High reflection coefficient ~ 1.0. A true ultrafiltrate as glomerular capillaries are virtually impermeable to protein.
Oncotic pressure in the filtrate (Bowmans capsule) is 0mmHg.
Hydrostatic pressure is high & decreases little along the capillary (depends on balance between afferent & efferent
arteriolar constriction).

glomerular fluid moves out almost the entire length of the capillaries. This means the capillary oncotic pressure
increases along the capillary which is important for water reabsorption in the proximal tubule.

Typical values of Starling Forces in Glomerular Capillaries (mmHg)

  Afferent End Efferent End

Hydrostatic pressure in capillary (PGC)  60  58

Hydrostatic pr. in Bowman’s capsule (PBC) 15 15

Oncotic pressure in capillary (pGC) 21 33

Oncotic pressure in Bowman’s capsule (pBC) 0 0

Net Filtration Pressure 24 10

The flux equation discussed earlier simplifies to the following: GFR = Kf x (PGC - PBC - pGC)

3. Intestine
In the intestine fluid moves into the capillaries along almost their entire length - low hydrostatic pressure and low
reflection coefficient

4. Hepatic sinusoids - very permeable to protein, with low 'reflection coefficient' and subsequently higher
interstitial oncotic pressure.

5. Brain – capillaries are impermeable to proteins (like other capillaries) but also to low molecular weight solutes.
Na & Cl ions (make up the majority of these solutes) are capable of exerting an osmotic force, which can be
huge in comparison to oncotic pressures. A 1milliosm increase in osmotic gradient between blood & brain ISF
can exert a force of 17-20mmHg small changes in plasma tonicity can have a marked effect on cerebral
volume.

6. Pulmonary capillaries
Features - gas exchange is the prime function of the lung & is facilitated by the close association of the pulmonary
capillaries with the alveoli (blood-gas barrier). Pulmonary blood flow = CO flow is large. The pulmonary
capillary blood volume is about 80 mls. The blood-gas membrane is thin with a large SA (the capillaries form a
dense network in the alveolar walls which is almost a continuous thin film of blood) which minimises the barrier to
diffusion. The pulmonary pressures are much lower than in the systemic circulation and the pulmonary vascular
resistance is very low. The pressure is just sufficient to perfuse the apical areas of the lungs in the erect healthy
adult.

Typical values for the Starling’s Forces in Pulmonary Capillaries

Capillary hydrostatic pressure (Pc) is 13 mmHg (arteriolar end) to 6 mmHg (venous

end) but variable because of the hydrostatic effects of gravity esp in the erect lung.

• Interstitial hydrostatic pressure (Pi) - Variable but ranges from zero to slightly
negative.

• Capillary oncotic pressure = 25 mmHg (same as systemic capillaries)

 • Interstitial oncotic pressure = 17 mmHg (estimated from lung lymph)

Oncotic pressure gradient - the interstitial oncotic pressure is high indicating significant leak of protein (mostly
albumin) across the thin capillary walls. Reflection coefficient  0.5. Considering the typical values and allowing for
the reflection coefficient, it can be estimated that the net oncotic gradient is small but favours reabsorption.
Hydrostatic pressure gradient - the capillaries are ‘intra-alveolar vessels’ and the presssure they are exposed to is
close to alveolar pressure (which has an average value of zero). However, actual measurements of pressure in the
alveolar interstitium have found slightly negative pressures (e.g. -2 mmHg). Closer to the hilum, the interstitial
pressures become more negative and this favours flow of fluid from the alveolar intersitium into the pulmonary
lymphatics. The capillary hydrostatic pressure is variable because of the effects of gravity. In the erect lung the
pressure in the vessels at the base of the lung is higher than the pressure at the apex. The pressure difference is
equivalent to the height of a static water column from the base to the apex = 30cmsH2O (23 mmHg). If the typical
pulmonary artery pressure is 25/8 then it is apparent that the pressure is just adequate for perfusion of the apex of the
erect lung. The pulmonary circuit has a low resistance and about half of this resistance is due to the pulmonary
capillaries which have no muscle in their walls. The capillary hydrostatic pressure is quickly affected by changes in
pulmonary artery pressure and left atrial pressure without much protective buffering.

Overall balance of Starling forces - is generally stated as favouring reabsorption because of the clinical fact that
the lungs are generally ‘dry’ and clearly need to be to facilitate gas exchange. Under normal conditions, there is a
small net outward movement of fluid. This is estimated as equal to the pulmonary lymph flow rate  10-20 mls/min
or 2%blood flow. So despite the net outward hydrostatic pressure gradient and the high reflection coefficient which
limits the effectiveness of the oncotic pressure in opposing outward fluid movement, the measured low lymph flow
means that the balance of forces is clearly to minimise loss of fluid into the interstitium.

The interstitial fluid move towards the hilum along the spaces beside the vessels and the airways. Facilitated by the
interstitial hydrostatic pressure becoming more negative as the hilum is approached & rhythmic external
compression that occurs during ventilation and one way valves.

Clinically – physical examination & CXR are more useful because it is not possible to measure all six of the
unknown values. Bedside determination of interstitial hydrostatic & oncotic pressures and the reflection coefficient
is not possible. Plasma protein concentration gives an index of capillary oncotic pressure and values obtainable from
use of a pulmonary artery catheter (eg wedge pressure as estimate of LAP & mean pulmonary venous pressure).

Safety Factors Preventing Pulmonary Oedema

Excess fluid must first accumulate in the interstitium (interstitial oedema), then must move into the alveoli (alveolar
flooding). The lung is relatively resistant to this because…
1. fluid filtration lymph flow to remove the fluid.
2. Oncotic buffering mechanism: when filtration increases, the albumin loss in the filtrate decreases. This
combined with the increased lymph flow washes the albumin out of the interstitium  interstitial oncotic
pressure. Does not work if the capillary membrane is damaged e.g. sepsis. .
3. High interstitial compliance: large volumes of fluid can accumulate in the gel of the interstitium without
much pressure rise. Eventually the interstitial tissues become full  pressure + alveolar flooding

These safety mechanisms are quite effective especially in preventing pulmonary oedema associated with rises in
capillary hydrostatic pressure. It has been estimated that the capillary hydrostatic pressure can rise to three times
normal before alveolar flooding occurs. Surfactant assists in the prevention of alveolar flooding also.
99A8 Explain the significance of plasma oncotic pressure in capillary fluid dynamics. 75%
Above & fluid section. Need to define osmotic pressures & explain concept of oncotic pressure.

Explain the local effects of a decrease on plasma colloid osmotic pressure in the skeletal
97B1 64%
muscle capillary bed
04B16 76%
Explain the physiological processes involved in the development of interstitial oedema
01B8 46%

Peripheral oedema formation

Interstitial oedema = fluid in the interstitial spaces.
It can be localized (e.g. secondary to isolated venous or lymphatic obstruction) or systemic (diffuse or occur at sites
of highest hydrostatic pressure i.e. dependent oedema - typical of CCF).

Interstitial oedema occurs when net filtration > capillary reabsorption and lymphatic drainage
 Imbalance of hydrostatic forces…
1. Increased capillary hydrostatic pressure forces fluid out of
vessels e.g. arteriolar dilation or venoconstriction/venous
obstruction.
2. Decreased interstitial hydrostatic pressure - negative
pressure pulmonary oedema.
 Imbalance of osmotic forces…
Decreased plasma osmotic pressure reducing movement of
fluid into the vessels e.g. oncotic pressure –
hypoalbuminaemia, malnutrition, protein nephropathies.
Increased interstitial oncotic pressure
 ECF e.g. Primary sodium retention (activation RAS in
cardiac failure)  ECF volume,  hydrostatic pressure & 
osmotic pressure, fluid resuscitation with renal failure
 Lymphatic obstruction  inadequate removal ISF e.g.
metastatic disease, node dissection, filiarisis (parasitic
infection)
 Decreased reflection coefficient – inflammation, allergic
reactions, sepsis & burns (permeability to proteins), hepatic
sinusoids which are normally very permiable thus interstitial oncotic pressure increases.

Consequences of oedema
Increased interstitial fluid volume decreases diffusion of oxygen and nutrients from the capillary to the cell.
V: CONTROL OF CIRCULATION
Control of cardiac output
Chemoreceptors in the cardiovascular system
Carotid & aortic arch chemoreceptors exert their main effects on respiration, however they also converge on the
vasomotor area  vasoconstriction & bradycardia. Hypoxia also causes hyperpnea & catecholamine secretion 
tachycardia & CO. Heamorrhage & hypotension stimulates chemoreceptors due to stagnant anoxia.
Cushing Reflex- Hypoxia & hypercapnia both stimulate the vasomotor area directly. With intracranial pressure,
blood supply to the vasomotor area is compromised & local hypoxia & hypercapnia increase its discharge. This
leads to systolic BP which leads to bradycardia (reflex from arterial baroreceptors) & is why bradycardia occurs
with ICP.

A: Role of the vasomotor centre & the autonomic nervous system in the regulation of CO + VR
Describe the autonomic innervation of the heart and the direct effect of autonomic
99A7 59%
stimulation on the heart.

The heart receives both sympathetic and parasympathetic

supply, with the balance of each supply determining the
overall effect on cardiac function.

Vasomotor centre - in the medulla and lower 1/3 of pons.

SNS & PNS make up the 'cardiac plexus', which has
cardiac (supplying pacemaker, conduction and
contractility portions of the heart) and coronary
(supplying coronary vasculature) portions.

 Sympathetic supply
Location - lateral portions of vasomotor center (rostral
ventral lateral medulla)  thoracic IML (preganglionic)
& synapse in paravertebral sympathetic ganglion chain
(C6-7 & T1-6)  post-ganglionic fibres innervate the
heart.
Supply - all areas of the heart, particularly the ventricular
muscle. Left sided fibres predominately control
contractility, and right sided fibres effect heart rate.
Mechanism
1. Release of NA  1 + 2 adrenergic receptors
(muscle & conduction fibres)  cAMP levels
→ activates protein kinase A → phosphorylation
of voltage dependent Ca channels which
increases opening times → increases Ca release
→ contractility. membrane permeability to
Na+ and Ca2+. Influx  cell depolarisation,
speed of pace-maker cell automatic
depolaristion,  excitability of cells (easier to
depolarise and thus conduct AP), speed of AP
conduction and contractility of contractile cells.
2. Release of NA  1, 2 + 2 adrenergic
receptors (coronary arteries)

 Parasympathetic supply – predominates

Location – preganglionic fibres originate from medial
portion of vasomotor center (near dorsal motor nuclei &
nucleus ambiguous), travel in vagus nerve & synapse on
or near the heart.
Supply - predominate supply of SA (right vagus) and AV
(left vagus) nodes & some atrial supply. Little direct
ventricular supply.
Mechanism - release of ACh from nerve endings 
interact with muscarinic 2 & acting via Gi-protein 
opens K+ channels  K+ permeability  K+ efflux & hyperpolarisation. Also cAMP production by adenylate
cyclise  slower opening of Ca2+ channels. This reduces the excitability of the cell, slowing the automatic gradual
depolarisation of the pace-maker cells (as must now reach threshold voltage from an even more negative membrane
potential) and reduces the speed of AP conduction through.

Effects on cardiac function: Net effect is determined by the balance between SNS and PNS outflow. Both SNS
and PNS innervate each other, allowing inhibitory modulation of one pathway by the other.
SNS activation PNS activation
SA node SA firing rate, HR Right vagus - HR, possible sinus arrest if PNS outflow
great enough and no SNS antagonism. Membrane
potential may decrease from -55 to -60mV → -65 to
-70mV
Atria contractility, conduction velocity, contractility, often  conduction velocity
atrial assisted ventricular filling
AV node  conduction velocity Left vagus -  conduction velocity

His-Purkinje  conduction velocity  conduction velocity

system
Ventricles  contractility  contractility
Coronary  coronary blood flow  more forceful
Arteries systole and cardiac acceleration

B: Function of baroreceptors & relate this to common clinical situations

1992 Write short notes on volume receptors  
03B10 57%
Describe the role of baroreceptors in the control of systemic arterial pressure.
00B1 54%
Role of Baroreceptors 5 – sensing intravascular volume
Baroreceptors – stretch receptors in the walls of
the heart & blood vessels. Play a key role in the
sort-term adjustments of blood pressure when
abrupt changes of blood volume, CO or PVR
occurs (e.g. haemorrhage, standing and exercise)
through the baroreceptor reflex.

Baroreceptors are stimulated by distension of the

structures in which they are located and
discharge at an increased rate if the pressure in
those structures rises

 High pressure Baroreceptors

Location: Carotid sinus (small dilation of the
internal carotid just above the common carotid
bifurcation), aortic arch & adventitia of large
arteries in thorax + neck contain baroreceptors
that monitor arterial circulation.

Mechanism: Afferent nerves from these receptors discharge at a low rate at

normal BP. When distended by BP their discharge increases & vice versa.
Respond to stretch & rate of stretch (changes in pressure, sustained pressure,
& pulse pressure).
Respond more strongly to a rapidly changing pressure than a constant
pressure.
Respond to beat-to-beat fluctuations in BP e.g. on standing when BP
momentarily falls.

Steady increase in rate of firing from 60 mmHg or 90 mmHg, up to a

maximum of 180 (carotid body) or 210 mmHg (aortic arch).
Afferent nerves via nerve of Hering (branch of glossopharyngeal from carotid body) & vagus (aortic arch) 
nucleus tractus solitarius of medulla  inhibitory fibres to vasomotor centre (regulates SNS activity of the
vasoconstrictor nerves) & excitatory fibres to vagal nuclei (regulates PNS activity)  vasodilation, venodilation,
bradycardia, BP & CO. Fall in BP has the opposite effect.
By coupling sympathetic and parasympathetic activation and inhibition, the baroreflex maximizes its ability to
control blood pressure

Chronic hypertension - sustained BP for 1-2days results in 'resetting' of the baroreceptors with a decrease in firing
rate. counteracts temporary disturbances, but cannot regulate arterial pressure in the long term because the
baroreceptor firing rate adapts to prolonged changes in arterial pressure.

Valsalva manoeuver - a crude but quick clinical test of baroreceptor function and associated ANS pathways.

 Low pressure Baroreceptors (cardiopulmonary receptors)

Location: Atria walls, pulmonary circulation & large veins (venae cava).
Mechanism: When ECF volume falls, CVP declines  firing of atrial stretch receptors & vasopressin secretion.
Sympathetic activity increases  renin release  Na & water retention via angiotensin & aldosterone
When ECF volume rises, CVP increases  wall stetch & vasopressin inhibition. PNS activity  RAS activity.

Important in minimising BP changes in response to changes in blood volume & involved in long term BP control.

CVS effects of - 1L Normal Saline *See fluid section

 1L Autologous blood 2L whole blood 1L haemocel

Initially
Blood volume 20%
Ciculation is overfilled & mean systemic pressure increases (15mmHg with 1L transfusion)
RAP up to  7mmHg
CO 10-15L/min due to preload & HR.
SVR initially normally CO  BP

CVS responses lead to venous pooling of blood & capillary fluid loss to ISF
High pressure carotid sinus baroreceptors – sense BP & increased inflow from them  outflow from
vasomotor centre  venodilation & mean systemic pressure. Venous pooling  VR & CO & returns BP towards
normal.
Tissue pressure & metabolic autoregulation adjust vascular resistance to maintain constant tissue blood flow.
capillary hydrostatic pressure  ISF – minimal amount as oncotic pressure of transfused blood limits its
distribution to the intravascular compartment.

Excretion
BP  pressure diuresis & natriuresis. Occurs despite autoregulation because PVR (2 vasoconstriction from
autoregulation)  arterial BP.
Stimulates low pressure volume receptors - ADH & water diuresis
O2 carrying capacity  EPO production & synthesis of new RBC
C: Role of the autonomic nervous system in controlling SVR & redistribution of blood volume
Control of blood pressure
Neural factors affecting arteriolar tone
All blood vessels (except capillaries & venules) contain smooth muscle & receive motor nerve fibers from the SNS.
Fibres to resistance vessels regulate tissue blood flow & arterial pressure. Fibres to venous capacitance vessels
regulate the volume of blood stored in the veins.
Noradrenergic fibres are vasoconstrictor in function. Skeletal muscles are innervated by cholinergic sympathetic
vasodilators. Fibres form plexuses on the adventitia of arterioles. Varicosities extend to the media & end on the
outer surface of the smooth muscle – current spreads via gap junctions. There is some tonic discharge in vasodilator
fibres & most vasodilation is produced by decreasing this discharge.

Arterial pulse
The blood forced into the aorta during systole  forward motion of blood in vessels & creates a pressure wave that
travels along the arteries. The expansion of the artery walls is palpable as a pulse. It travels at a greater velocity than
blood flow. The pulse strength is related to the pulse pressure, not the mean pressure. It can be thready (shock),
strong (SV e.g.exercise), collapsing (aortic insufficiency).

Arterial pressure
The pressure in large arteries is normally systolic(120mm/Hg)/diastolic(70mm/Hg). The pulse pressure =
difference between the systolic & diastolic pressures. The mean pressure is the average pressure throughout the
cardiac cycle & this is usually slightly less than halfway because systole is shorter than disatole.
Pressure falls rapidly in the small arteries & arterioles because of their higher resistance & this varies considerably
depending on if they are constricted or dilated.

Medullary control of BP

Vasomotor control
The sympathetic nerves controlling HR & SV discharge in a tonic
fashion and BP is adjusted by varying the rate of this tonic discharge.
The main control of BP is exerted by neurons in the vasomotor
centre of the medulla. These neurons project to the
interomediolateral gray column of the thoracic cord & release
glutamate. They also project to the nucleus ambiguous + vagal nerve
to change HR.
discharge  arteriolar constriction, HR + stroke volume 
CO & BP
 discharge  vasodilation  BP

Factors affecting activity of the vasomotor centre

Chemicals – CO2, H+, O2
Baroreceptors – lung & carotid
Neural – cortex via hypothalamus
Chemoreceptors

Descending tracts from the limbic area in the cerebral cortex (via the
hypothalamus) are responsible for the changes that occur with
emotions – anger, excitement.
Lung inflation – vagal afferent discharge  vasodilation  BP
Pain – afferent impulses in the reticular formation  BP, however
if it is severe & prolonged  vasodilation  BP
E: Neural & humoral regulation of blood volume & flow
1993 Briefly discuss the humoral factors that control blood pressure  

Hormonal control of BP
Systemic regulation by hormones
Vasodilators
1. Kinins – work via NO. Formed during active secretion in sweat glands, salivary glands & the pancreas.
2. ANP – antagonizes many vasoconstrictor substances & lowers BP.

Vasoconstrictors
1. Vasopressin – potent vasoconstrictor, but also CO little change in BP.
2. Noradrenaline – generalized vasoconstrictor action. Much more important action through sympathetic
vasoconstrictor nerves, than their action as a circulating hormone.
3. Adrenaline – dilates vessels in skeletal muscle & liver
4. Angiotensin II – secreted with ECF volume & vascoconstrictor action helps to maintain BP

Neural control of BP
Systemic regulation by the nervous system
Blood Vessels…
All blood vessels (except capillaries & venules) contain smooth muscle & receive motor nerve fibers from the
sympathetic ANS. Fibres to resistance vessels regulate tissue blood flow & arterial pressure. Fibres to venous
capacitance vessels regulate the volume of blood stored in the veins.
Noradrenergic fibres are vasoconstrictor in function. Skeletal muscles are innervated by cholinergic sympathetic
vasodilators. Fibres form plexuses on the adventitia of arterioles. Varicosities extend to the media & end on the
outer surface of the smooth muscle – current spreads via gap junctions. There is some tonic discharge in vasodilator
fibres & most vasodilation is produced by decreasing this discharge.

Heart…
Impulses in NA sympathetic nerves HR, contractility & inhibition of vagal effects (vagal discharge at rest is
greater than sympathetics discharge).

Local factors affecting arteriolar tone

Substances released by the endothelium: Local Factors
1. Prostoglandins – prostocyclin  vasodilation & inhibition of
platelet aggregation
2. Thromboxanes – thromboxane A2 (from platelets) 
vasoconstriction & platelet aggregation
3. NO (endothelium derived relaxing factor)  vasodilation.
Triggered by many factors including ACh, bradikinins
&cytokines. It diffuses to smooth muscle & produces cGMP
which mediates vascular smooth muscle relaxation. Is co-
released when many factors act on the endothelium to allow
large arteries to also dilate & to help keep blood vessels with
intact epithelium patent (when damaged areas are producing
substances  vasoconstriction)
4. Endothelins – polypeptides that  vasoconstriction

Metabolic Theory
P PCO2
O PO2
O osmolality
H hydrogen
T temperature
A adenosine
L lactate
K potassium
Myogenic Theory
Myogenic theory of autoregulation – as pressure rises, vessels are distended and they have an intrinsic response to
contract. (Law of Laplace).
F: CVS responses to exercise Physiological changes with exercise -
 Exercise Requires the Coordination & extensive alterations of most of the Body's Organ Systems
Muscular and skeletal systems.
Cardiovascular & respiratory systems deliver O2 & fuel, remove wastes & heat .
Skin gets rid of heat through radiation & evaporation.
Nervous & endocrine systems monitor & coordinate the other systems.

 Exercise Creates a Demand for Fuel and O2

O2 consumption - we can exercise vigorously for only a few seconds using the stored ATP & creatine phosphate.
Any exercise over a few seconds requires aerobic respiration to provide enough energy. O2 consumption goes up
with intensity of exercise because aerobic metabolism must be used to generate ATP. O2 consumption of skeletal
muscle is increased x100 fold. Whole body O 2 consumption x20-25 in trained atheletes. Maximum sustained
oxygen consumption (VO2max) is a good measure of endurance in athletes.
Anaerobic glycolysis - Muscles can also enter O 2 debt through anaerobic glycolisis. Anaerobic glycolysis gives
only 2 ATPs/glucose while aerobic respiration gives 36 ATPs/glucose.
Fuel - Glycogen is the main initial fuel source. SNS activity causes glycogen breakdown to glucose. Liver releases
glucose into the blood to supply muscles & brain. As exercise continues more and more fat is used for fuel.
Triglycerides hydrolyzed to produce fatty acids & glycerol.

Fuel for Exercise  Amount Stored:  Amount Stored: Rate of Use

Fuel Time Distance (Power)
enough for about enough to go
 ATP & CP  Fastest
10 sec about 100 yards
glycolysis medium
 Carbohydrates  enough for about  enough to go
fast;
(glycogen) 2hrs about 20 miles
respiration slower
 Lipids  enough for about  enough to go
 very slow
(triglycerides) 40 days about 1000 miles

 Respiratory Changes
RR - from 15 breathes/min to 60 breathes/min
TV - from 0.5L/min to 2 L/min . The maximum possible tidal volume is the
vital capacity, but it is too fatiguing to breath in and out for long at full vital
capacity.
TV & RR  minute ventilation from 7.5 L/min to >100 L/min
The stimulus for increased respiration in exercise is not known. CO2 is a
powerful stimulator of respiration, but it does not rise much in exercise.
Stimulus may be increased blood K or impulses from muscle proprioceptors.
Respiration is usually not the limiting factor in endurance exercise

 Temperature regulation
Exercise results in a rise in temperature because heat production overwhelms the
hypothalamic heat-dissipating mechanisms. Loss occurs at the skin, in expired
air & sweat production & vaporization.
As exercise progresses skin blood flow increases to remove excess heat.
Enormous amounts of heat may be removed by sweating & if ambient
temperature is above body temperature sweating is the only method of heat loss

 O2 Delivery in the Tissues is Promoted by Acid Conditions (Bohr Effect)

Muscle metabolism produces large amounts of acids: Aerobic conditions sugars and fats are burned to CO2, which
dissolves to form carbonic acid. Anaerobic conditions (maximal exercise) lactic acid is formed. Both lower the pH.
pH & temperature shifts the haemoglobin dissociation curve to the right more O2 is given up by the blood.
Normally only 25% is unloaded, but during exercise as much as 75% may be unloaded.
 CVS responses to exercise 2
Systemic changes - in isotonic exercise (because relaxation occurs allowing blood flow through the muscles)
sympathetic discharge  contractility & HR & stroke volume  CO
Mobilisation of blood from splanchnic areas also contribute to 30%
amount of blood in the arterial circulation.
The Frank-Starling mechanism also contributes - VR (2 pumping
action of muscles * respiration)  venous pressure & diastolic
inflow  ventricular end-diastolic pressure  contractility & SV.
In heart transplantation CO rise still occurs through the Frank-Starling
mechanism & circulating catecholamines contribute.

HR - from 60 beats/min upto 200 beats/min

SV - from 80 mL/beat to 150 mL/beat (in athletes)
CO – from 5 L/min to nearly 30 L/min
BP - CO causes the systolic BP to rises moderately (upto 180mmHg),
whereas the diastolic remains unchanged.
TPR due to vasodilation of vessels

Local changes - Skeletal muscle blood flow

When skeletal muscle contracts it compresses vessels at 10% of
maximal tension & flow ceases at 70% of maximal tension. Between
contractions flow is so greatly increased that flow can be as much as
x30 fold. It increases at or even before the start of exercise, so initially
is probably a neurally mediated response. Blood flow in resting muscle
is 2-4mL/100g/min & this doubles after sympathectomy some
decrease in tonic vasoconstrictor may occur.
Metabolic autoregulation - once started local mechanisms maintain
the high flow - tissue O2, tissue CO2, temperature (due to the heat
of metabolism in active tissues), K+ accumulation, lactate & other
vasodilator metabolites. Dilation of arteriorles & precapillary
sphincters produce a x10-100 fold increase in the number of open
capillaries. The dilation increases the cross sectional area & the velocity of flow decreases.
Capillary pressure increases until it exceeds the oncotic pressure & accumulation of osmotically active metabolite
decreases the osmotic gradient favouring fluid transudation into the interstitial spaces. Lymph flow also increases
to limit interstitial fluid build up.

Alterations in distribution of CO
In exercise more blood is shifted to muscle and heart tissue; less blood goes to the viscera and tissues not needed at
the moment. Flow to skin is initially reduced but is later increased to get rid of excess heat,
 Tissue  Rest L/min  Exercise L/min
 Viscera 1.2  0.6
 Muscle & Heart  1.0  26.0
 Other  2.8 3.4
 Total  5.0  30.0

The cardiovascular system may be the limiting factor in endurance exercise. Limits to CO increase:
No matter how much you train you cannot exceed upper limits on HR and SV. HR is limited to about 200 beats/min-
if the beat is faster there will not be enough filling time. SV is limited by sarcomere length & the strongest
contraction is at intermediate length. Overfilling  heart muscle stretch & weaker contraction.

Training – CO (through SV) & O2 extraction are increased in trained individuals. There are more mitochondria in
muscle fibres & more capillaries distributed to the fibres.
Summary of Physiological Adjustments to Exercise in a trained athlete
G: CVS responses to pregnancy
CVS changes pregnancy

CARDIOVASCULAR responses to pregnancy

1. HR - 17% 1st trimester, 25% middle 3rd trimester
2. SV – 20-30% 1st trimester
3. CO – progressive increase, 40-45% at 12-28w, 50% 32-36w, then 47% above nonpregnant levels. Due to
VR 2 venodilation & vascular volume 2 oestrogens.
 Uteroplacental circulation - 750mL/min at term
 Renal blood flow - 80% 1st trimester, may fall slightly towards term
 breast, skin & GIT blood flow
4. Blood volume – 35-40% at term = 1000-1500mL.
Plasma volume – 45% 2 sodium & water retention due to oestrogen stimulating the renin-angiotensin
system.
RBC volume – 20% due to eryhtropoietin synthesis
Haematocrit – 33% = physiological anaemia
5. PVR – 30% 12w, 35% 20w, then 30% below nonpregnant level. Due to progesterone & prostaglandin
mediated vasodilation and down regulation of -receptors. Vasodilation in many tissues – kidney, gut,
heart, breasts, skin. Cerebral blood flow is unaltered. Placenta acts as A-V shunt.
6. MAP – 10% systolic & diastolic BP, nadir at 20w
7. Colloid oncotic pressure  oedema
8. CVP & pulmonary capillary wedge pressure - unchanged

Aortocaval compression syndrome – compression of IVC by gravid uterus  VR  CO. Blood returns to the
heart via the paravertebral epidural veins draining into the azygous vein. Uterine perfusion is decreased due to
uterine venous pressure. Aorta compression can also occur  uterine artery hypotension & decreased
uteroplacental perfusion.
Incidence – 15% at term, can occur at 20w
Symptoms – hypotension, palloer, nausea & vomiting when supine
Prevention – positioning mother on L side

Labour
Uterine contraction  injection of 300ml blood from the uterus into the maternal circulation & systolic & diastolic
BP by 10-20mmHg.
CO – 15% latent phase, 30% active phase & 45% expulsive phase of labour. Immediately post delivery it is 60-
80% above the prelabour value 2 autotransfusion & VR due to uterine involution.
CO & arterial blood pressure return to nonpregnant values 2weeks post delivery.
H: CVS responses to anaesthesia & central neural blockade
Effect Halothane Isoflurane
HR HR  (carotid sinus & sinus node depression HR – due to MAP & baroreceptor response
from vagal stimulation). Obtunds baroreceptor
reflexes (should actually due to MAP).
CO & SV CO – 2myocardial contractility (inhibition CO unchanged (normocapnic ventilated) – contractility,
of Ca2+ ion flux & Ca2+ interaction with but vasodilates. RAP 2 to peripheral vasodilation
contractile proteins).
MAP MAP – 2myocardial contractility & CO MAP – 2SVR
SVR No change - vasodilates in brain & skin, but is SVR reflects increased skeletal muscle (x4 fold) &
offset by vasoconstriction elsewhere. cutaneous blood flow
Conduction Sinus node depression from vagal stimulation.
Threshold potential & refractory period
Other Most potent trigger of malignant hyperthermia Coronary steal syndrome (rare) – dilation of small
coronary resistance vessels maldistributes blood from
ischaemic to nonischaemic areas.
Drug Arrythmias – sensitises to circulating
interactions catecholamines  dose of adrenaline
necessary to cause dysrhythmias

PROPOFOL KETAMINE
General Direct stimulation of CNS  sympathetic outflow.
CVS effects resemble sympathetic stimulation
BP Inhibition of sympathetic vasoconstrictor nerve activity  systemic + pulmonary BP
PVR  SBP 15-20% CVP
Vasodilation – due to production & release of NO
BP effects exaggerated – elderly, hypovolaemia, impaired **As is a central response if high doses of CNS
LV function. Attenuates response to laryngoscopy. depressants are used CVS depression can occur
CO CO 20% - due to PVR & BP CO.
Critically ill patients can BP & CO due to depletion
of catecholamine stores + exhaustion of SNS
compensatory responses
Ionotropy Negative ionotrope - intracellular Ca 2 inhibition of
transsarcolemmal Ca influx.
HR Often unchanged, but bradycardia can occur (as HR
SNS>PNS activity). Profound bradycardia & asystole Baroreceptor function well maintained.
occurs in 1.4/100000.
Work/O2  cardiac work & myocardial oxygen demand
demand Can worsen IHD
CNS cerebral blood flow + ICP. cerebral blood flow 60% & ICP.

Physiologic Effects of spinal anaesthetic

SNS blockade  arteriolar vasodilation, but BP does not drop proportionally because of compensatory
vasoconstriction in areas with intact SNS (e.g. upper extremities). The decreases in systemic vascular resistance is
<15%. This is because arterioles retain some intrinsic tone & do not dilate maximally.
Venules do not maintain intrinsic tone & dilate maximally  vascular capacitance  VR to the heart  CO &
systemic BP. This can cause profound hypotension if the patient is hypovolaemic. Use of an -agonist & slight head
down position can minimise unexpected cardiac arrest.
Blockade of preganglionic cardiac accelerator fibers (T1-T4)  HR. This is accentuated by decreased VR & CVP
which decreases stimulation to intrinsic stretch receptors in the R atrium.
Myocardial oxygen requirements are decreased 2VR, HR & systemic BP.
Apneoa that occurs with excessive spinal anaesthesia is likely due to ischaemic paralysis of the medullary
ventilatory centers due to profound hypotension & associated decreases in cerebral blood flow. Rarely it is due to
phrenic nerve paralysis. Ventricular CSF [LA] are too low to effect the ventilatory centres.
VI: REGIONAL CIRCULATION

A: To describe the relationship between organ blood flow & demand & the role of autoregulation

B: To describe features of the coronary circulation & clinical significance of them

Coronary blood flow 4
Coronary blood flow - at rest is 250ml/min = 5% CO

Coronary blood flow anatomy

Supply - the coronary arteries arise from sinuses between the 2 cusps of the aortic
valve at the root of the aorta. Eddy currents keep the valves away & the orifices are
patent throughout the cardiac cycle.
Right coronary artery  R ventricle & atrium
Left coronary artery  L ventricle & atrium

Drainage - through the coronary sinus 90% + anterior cardiac veins.

1997A8 List the determinants of coronary artery blood flow. Briefly compare phasic coronary blood flow in
51% 
the left and right coronary arteries.
Coronary artery blood flow 5 – left vs. right 2, coronary artery flow curves, coronary perfusion pressure
The coronary circulation (like the lung and brain circulation), is an example of a Starling resistor – the extravascular
compression on coronary vessels thus have to be taken into account because
the heart compresses its blood vessels when it contracts.
Left ventricle - the pressure in the L ventricle (121mmHg) is slightly
higher than the aorta (120mmHg) during systole flow ceases in the
subendocardial part during systole (the outer portion has flow, because the
pressure is somewhat disipated).
Right ventricle – because of lower pressures in the R ventricle the
differences in flow between systole & diastole is less marked.

Coronary perfusion pressure – driving pressure for the coronary

circulation. Usually aortic diastolic – larger of LVDP or RAP (because both
of these are much less than aortic diastolic it is often said it equals aortic
diastolic pressure).
LV systole = aortic systolic pressure – LV intraventricular pressure
= 120 – 121 = -1mmHg
LV diastole= aortic diastolic pressure – RAP
= 80 – 5 = 75mmHg
RV systole = aortic systolic pressure – RV intraventricular pressure
= 120 – 25 = 95mmHg
RV diastole= aortic diastolic pressure – RAP
= 80 – 5 = 75mmHg
Significance - Left coronary artery flow is RATE dependent: HR   diastole + L coronary flow.moreover the
L ventricle has greater flow 2 to muscle mass. The L subendocardium is most susceptible to ischaemic damage. In
aortic stenosis higher pressures must be generated in the L ventricle greater coronary artery compression occurs &
myocardial O2 consumption is greater  greater rates of ischaemia. In CCF rises in venous pressure  reduced
effective perfusion pressure.

Control of coronary blood flow

The caliber of coronary vessels & hence rate of flow is influenced by physical factors (viscosity, aortic pressure +
frictional resistance of walls), metabolic autoregulation & neural factors. Metabolic autoregulation overcomes all
other influences.

Exercise – coronary blood flow can x4-5 to 1000-1250mL/min due to metabolic autoregulation (POOHTALK).
Any SNS mediated vasoconstriction is overcome by autoregulatory vasodilation.

Coronary perfusion pressure

Coronary Blood Flow = -----------------------------------
Coronary Vascular Resistance

02B11 Outline the factors that determine coronary vascular resistance 65%
CVR = coronary vascular resistance
CPP = coronary perfusion pressure
CBF = coronary blood flow

Factors that determining resistance are expressed by the Hagan-Poiselle’s equation

Resistance = 8l
r4

 = fluid viscosity
l = vessel length
r = vessel radius

Assuming length remains constant, CVR can be determined by

A) Viscosity of blood
  e.g. polycythaemia will  CVR

Resistance is inversely proportional to the 4th power of radius – slight change in vessel radius will have a large
inverse change in resistance.

B) Factors determining coronary vessel radius

1) Extravascular compression - Coronary vessels are exposed to ventricular pressure, hence extravascular
compression will  r therefore  resistance. The effect is marked in the LV due to its higher pressure – no
flow during systole, max flow during diastole. RV – continous flow throughout cardiac cycle.
2) Metabolic autoregulation - direct relationship between myocardial O2 metabolic activity & myocardial
blood flow.
3) Pressure “Myogenic” autoregulation – to maintain a constant CBF in the face of changing perfusion
pressure. With  CPP, coronary vessels detects the stretch in the SM resulting in a reflex contraction of the
SM to maintain the vessel radius and hence CVR. The reverse is true. This occurs at range of 60-180mmHg
4) Neural control
SNS  acts on  receptors (more  than  receptors in coronary vessels)  direct coronary vasoconstriction.
However, this effect is small as it is overriden by the metabolic auregulation. Sympathetic induced  myocardial
O2 demand (HR, contractility) and  O2 supply (diastolic time)  net result of indirect vasodilation   CVR
PNS – direct coronary vasodilator but again, overriden by metabolic autoregulation as the heart adjusts it
coronary flow to maintain the balance of O2 demand: supply ratio. PNS  HR, contractility  indirect
vasoconstriction   CVR

Measurement of coronary artery blood flow

Radionucleotides (thallium) distribution is directly proportionate to blood flow & areas of ischaemia can be
identified by their low uptake.

Coronary sinus PO2  20mmHg

This is low because the myocardial oxygen extraction ratio is high at 55-65%. The blood supply is low relative to its
O2 consumption if the heart requires more O2 coronary blood flow must increase.

95A4 The heart rate of a healthy 20 yr old goes from 55bpm to 130 bpm after receiving atropine IV.
40% 
03B9 Describe the effects of tachycardia on myocardial O2 supply and demand in a normal heart.

Determinants of myocardial oxygen supply and demand in a normal heart is as follows

Supply
- Arterial O2 tension
- Hb
- MAP (or DBP)
- Coronary vessel tone

Demand
- HR
- Contractility
- LV wall tension (preload and afterload)

Normal myocardial oxygen consumption is 7-9mls/100g/min. The O2 extraction is ~55-65% and the PO 2 in
coronary sinus is ~20mmHg.

Coronary perfusion – see above

Tachycardia HR >100
 O2 supply - in diastolic time &  L coronary perfusion time. The systolic:diastolic time ratio changes from 1:2 to
1:1. The RV is perfused during both systole and diastole hence tachycardia will have little effect on RCA perfusion.
 work done by the heart   myocardial O2 demand  coronary vasodilation from autoregulation (because
extraction ratio ~55-65% is high, the heart has to perfusion to O2 supply).
During exercise, cor blood flow x 4-5 (1000-1250ml/min) by metabolic autoregulation. This increase occurs
mostly during diastole.
C: To describe autoregulation in the cerebral circulation & factors that may affect it
Cerebral blood flow 9 CBF = Cerebral perfusion pressure/Cerebrovascular resistance

Normal - Cerebral blood flow  750mL/min or 50-54ml/100g/min  15% CO

CMRO2 = 3-3.5mL O2/100g/min or 50mL/min  20% basal O2 consumption

the brain has a very high metabolic rate & is extremely sensitive to hypoxia.
Critical cerebral blood flow in awake individual 18-20mL/100g/min. This 10mL/min with isoflurane anaesthesia.

Control of CBF 8 - depends on factors affecting…

 Cerebral perfusion pressure
The pressure driving flow of blood through the brain.
CPP = MAP – the greater of cerebral venous pressure or ICP.

Venous pressure in the head – in the upright position the venous pressure
above the heart is reduced by gravity. The neck veins collapse above the point
where the pressure is close to zero & their pressure remains close to zero. In
the head the dural sinus cannot collapse & its pressure is subatmospheric.
The pressure is proportional to distance above the collapsed neck veins & can
be –10mmHg. This must be recognized during neurosurgery as opening of the
venous sinus  air embolism.

ICP & Munroe-Kellie doctrine - explains that as the skull is a rigid vault of
fixed volume, any attempt to increase the volume within the skull (eg. due to a
space occupying lesion, such as a tumour) will result in a rapid rise in ICP. A rise in ICP will reduce the CPP and
thus CBF.

Nervous system – carotid barorecptors monitor mean carotid arterial pressure: MAP  SNS stimulation…
Heart  HR + contractility  CO & MAP
Vessel smooth muscle  peripheral vasoconstriction & venoconstriction  SVR & MAP
Both help to maintain CPP &  CBF. Important in moment to moment regulation e.g. changing from supine to
erect position.

Cushing Reflex – occurs with extreme hypoxia & maximal SNS stimulation occurs in an attempt to restore CBF &
oxygen supply to the brain.

 Cerebrovascular resistance
A decrease in CVR, increases CBF back to normal (as CBF = CPP/ Cerebrovascular resistance)

Autoregulation in the cerebral circulation - the capacity of tissues to regulate their own blood flow. Most vascular
beds compensate for changes in perfusion pressure by changing vascular resistance so blood flow remains constant.
1. Metabolic autoregulation – is the ability of a tissue to adjust its blood supply so that it receives sufficient flow to
carry out its functions. Due to locally released vasodilatory metabolite which accumulate in active tissues  vessels
dilation  blood flow  washing away of vasodilatory substances. Important for moment to moment regulation
of regional CBF (rather than global CBF).
Metabolic Theory: Vasodilator metabolites  relaxation of arterioles & precapillary sphincters.
P PCO2 tension - most pronounced in the skin & brain
O PO2 tension
O osmolality
H hydrogen or pH Histamine – in injured tissues

T temperature - fever & due to the heat of metabolism in active tissues

A adenosine
L lactate
K potassium– especially in skeletal muscle

Local vasoconstriction - injured vessels constrict strongly due to liberation of serotonin from platelets.

2. Pressure autoregulation – the ability to maintain constant CBF despite changes in MAP from  50-150mmHg
Mechanism: Myogenic theory of autoregulation – as pressure rises, stretch on vessel walls increases & vascular
smooth muscle responds by contracting  tone  radius + resistance  return to normal blood flow despite
increased pressure. Occurs within seconds. Opposite with BP

Rightward shift – occurs with chronic hypertension & acute sympathetic stimulation. As the lower limit is also
right shifted the patients will not tolerate a large drop in MAP without CBF.
Leftward shift – occurs in neonates, the plateau is narrower  30-90mmHg & the curve slopes upwards towards the
right. This is in keeping with their lower BP, but they are not able to tolerate higher BPs.

3. Chemical factors: pCO2 & pO2

Carbon dioxide – CBF increases linearly with changes between 20-
80mmHg, then flattens out. Change is  4%/mmHg. The CBF with
hypocapnia diminishes with time due to bicarbonate equilibration across
the BBB.

Oxygen – CBF increases when pO2 50-60mmHg. There is no increase

prior to this because there is not much decrease in O2 content of the
blood prior to these partial pressures because of the shape of the ODC. At
50-60mmHg the steep part of the ODC  O2 content & need for
CBF.
4. Nervous system – balance between SNS and PNS on vascular tone. Little role in altering CVR  5-10%, but
important in altering cerebral perfusion pressure.
BP– NA discharge occurs when blood pressure is markedly elevated. This reduces the passive increase in blood
flow & helps protect the BBB against damage.

Blood viscosity

Measurement of CBF 6
Fick principle using N2O (Kety-Schmidt technique) – values are obtained for the whole brain, regional variations
are not demonsatrated.
Radioactive Xenon – radioactive decay is measured over different parts of the head following inhalation or
injection of dissolved radioactive Xenon in a carotid artery. Allows detection of regional differences.
Extracranial Doppler flow probes – can measure regional flow.

Anatomy of the cerebral circulation

R+L Internal carotids and R+L Vertebral arteries which form the Basilar artery  Circle of Willis R+L anterior,
middle & posterior Cerebral Arteries  Venous Sinuses  Internal jugular + opthalmic + pterygoid venous
plexuses
There is normally no crossover between the 2 hemispheres & occlusion of a carotid artery usually leads to stroke.
There are precapillary anastomoses in cerebral arterioles, but flow is usually insufficient to prevent infarction.

D: To describe the renal circulation & its significance in maintaining renal function

See renal section

E: To describe the hepatic & splanchnic circulation

Blood reserviors
 Liver - contains ~ 15% of the circulating blood volume (25-30% of liver volume) and ~ 1/2 of this can be
rapidly mobilised during hypovolaemia. Contraction of arterioles can pump 500mL of blood into the systemic
circulation in less than a minute.
 Spleen – acts as a blood reserviour. There is smooth muscle in the splenic capsule & NA activity  strong
contraction & return of blood to the systemic circulation. This is unimportant in humans, but the reserviour of
the whole visceral circulation is important.

03A10 99A6 Describe the factors influencing hepatic blood flow. 55% 73%

Viscera & liver receive 30% CO  1500mL/min

Intestinal circulation – has extensive autoregulation & flow doubles after a

meal. Drains via portal vein to liver.

Hepatic blood flow – dual supply from

1. Hepatic artery 25%: 300 – 500 mls/min (mean pressure 90-100 mmHg)
Hepatic artery flow = MAP - hepatic venous pressure
Hepatic vascular resistance
2. Portal vein 75%: 1000-1200 mls/min (mean pressure 10mmHg)
Portal vein flow = portal venous pressure - hepatic venous pressure
 Hepatic vascular resistance

Hepatic Oxygen consumption  50ml O2/min

Hepatic artery 75% O2 Portal vein 25% O2

Hepatic acinus & portal triad – terminal branches of the hepatic artery, portal vein & bile duct drain into the
centre of an acinus. Hepatic artery and portal vein vessels anastomose to form sinusoids (mean pressure 2mmHg
greater than hepatic veins/IVC). Blood flows outwards to the central vein which eventually drains into the hepatic
vein (mean pressure 5mmHg) then inferior venae cava.  the periphery is the least well oxygenated area & most
susceptible to anoxic injury.

Control of liver blood flow

There is an inverse relationship between hepatic arterial & portal venous blood flow.

 Arterial system is a high pressure high resistance circuit under autoregulatory control
It can either increase or decrease blood flow by changing resistance. With hepatic artery pressure, flow is
maintained by hepatic arterial resistance until SBP< 80mmHg. If arteriole supply is not unopposed through
resistance it may result in slowing or reversing blood supply in the portal system.
Hepatic arterial buffer response - adenosine is produced by metabolism at a constant rate. When portal flow is
reduced it accumulates  hepatic arteriole dilation (autoregulation). This metabolic regulation allows the artery to
supply up to 50% liver blood flow if necessary.
Neural: α and β adrenergic and dopamine receptors. adrenalin → initial vasoconstriction (α effects) and then
vasodilation (β effects).

 Portal vein system is low pressure low resistance circuit with no autoregulation flow proportional to
pressure
Neural: α adrenergic and dopamine receptors. adrenalin → portal venous constriction
Portal vein radicles have smooth muscle in their walls & are innervated by  NA vasoconstrictor nerves. When
venous pressure rises radicles are passively dilated & the amount of blood in the liver rises – this congestion can be
extreme in CCF. If systemic BP drops, NA activity  constriction of portal radicles & portal pressure. Portal
blood flow is brisk through the liver & bypasses most of the organ to enter the systemic circulation.

Constriction of hepatic arterioles diverts blood from the liver & constriction of mesenteric arterioles reduces portal
inflow. In severe shock necrosis can occur because blood flow is compromised so much.

 Other Extrinsic Factors

Increased hepatic blood flow
Hypercapnia – ↑Portal venous blood flow
Glucagon
Feeding, VIP, Secretin

Decreased hepatic blood flow

Hypocapnia (↓ portal venous flow)
PEEP (↓ CO)
Vigorous exercise
Circulatory shock – portal blood is more significantly reduced than hepatic artery blood flow
Angiotensin II
Spinal / epidural anaesthesia (↓PVB flow and ↓ MAP)
Halothane and other inhalational agents (↑hepatic art resistance despite ↓ PVB flow)
Thiopentone, Propofol (dose dependent)
Vasopressin (v/c hepatic vasculature)
B adrenergic drugs
Venous congestion from heart failure
Raised intra-abdominal pressure

MAP  PHepatic Venous Pr essure Q Flow

Qhepatic artery  MAP Mean arterial pressure
RArteriole and Sinusoid P Pressure
R Resistance
Pportal venous pressure  Phepatic venous pressure
QPortalVein 
RPortal Vein Sinusoid

1 1 1
 
RArteriole and Sinusoid RArtriole RSinusoid
1 1 1
 
RPortal Vein and Sinusoid RPortalVein RSinusoid

F: To describe the skin circulation

Cutaneous circulation - flow can vary from 1-150mL/100g skin/min.
The oxygen and nutrient requirements of the skin are low & in contrast to most other body tissues, the factor
regulating cutaneous blood flow is temperature. The primary function of the cutaneous circulation is the
maintenance of internal body temperature.

Regulation of Skin Blood Flow

There are two types or resistance vessels in the skin arterioles & arteriovenous anastomoses.
 AV anastomoses
Shunt blood directly from arterioles to venules, bypassing the capillary circulation. They are found primarily in the
peripheries & have extensive SNS supply. AV anastomoses dilate maximally when denervated & full SNS
stimulation  complete cessation of flow. They have no basal tone & do not display autoregulation. They are highly
sensitive to circulating vasoconstrictors. The principal control is reflex nervous stimulation in response to activation
of the temperature receptors of the hypothalamus.
 Arterioles
The bulk of skin resistance vessels do exhibit some basal tone and are control by the CNS (predominates) and local
factors. NA & A elicit only vasoconstriction in cutaneous vessels. There are no PNS vasodilator nerve fibres, but
vasodilation is brought about by decreased constrictor tone & local production of bradykinin & vasodilator
metabolites. SNS-ACh stimulation of the sweat glands  vasodilation, possibly by the local production of
bradykinin.
Arterioles do display autoregulation of blood flow and reactive hyperaemia. Due to the low metabolic demand of the
skin, autoregulation is probably achieved by the myogenic mechanism.

Exercise - during exercise when temperature increases, cutaneous blood vessels dilate despite ongoing NA
discharge in other parts of the body.
Temperature - rise in hypothalamic temperature is a prepotent reflex that overcomes other reflex activity. Shock is
more profound in patients with elevated temperatures because of cutaneous vasodilation.
Severe cold - the reddened appearance of the skin on exposure to severe cold is due to the reduced O2 uptake by the
skin and the induced left-shift of the Hb-O2 curve.

White reaction – contraction of venular precapillary sphincters in response to a light mechanical stimulus. Onset
10-15sec, lasts 3-5mins.
Triple response – normal injury response & occurs with srtonger mechanical injury.
 1. Red reaction due to capillary dilation (3-15sec)
2. Flare due to arteriolar dilation (15-30sec) - caused by an axon reflex dilating neighboring arterioles
3. Wheal due to oedema (3-5mins) - increased permeability & extravasation of fluid due to direct trauma,
release of histamine & substance P.

G: To describe the muscle (skeletal) circulation

Circulation to muscle
The rate of blood flow to skeletal muscle varies directly with the contractile activity and the fibre type…
1. Fast-twitch - low oxidative, low capillary density muscle
2. Slow-twitch - high oxidative, high capillary density muscle

At rest precapillary arterioles exhibit asynchronous, intermittent contractions and relaxations  at any one time a
large portion of capillary bed is not perfused. The total blood flow to quiescent muscle ~ 1.4 to 4.5 ml/min/100g,
but with exercise the flow x15-20fold.
As muscle is the major body component by mass, and therefore has the largest vascular bed, its resistance plays a
major role in the regulation of TPR & BP. Cardiovascular Physiology

Regulation of Skeletal Muscle Blood Flow

1. Neural control – dominant at rest
Resistance vessels have high basal tone. Release of NA   receptor activation  vasoconstriction. (Adrenaline
in small doses activate 2  vasodilation, higher doses activate  vasoconstriction. Tonic activity of the SNS is
greatly influenced by activity of the baroreceptors. The vasodilation caused by their stimulation being the result of
inhibition of SNS activity.
Muscle is also supplied by vasodilator SNS-ACh fibres, which arise in the cerebral cortex and are thought to operate
before exercise, stress, etc.

2. Local control - dominant with exercise irrespective of the level of SNS activity
Metabolic autoregulation (POOHTALK)

Factors governing flow

1. Arteriovenous pressure gradient
2. Tissue pressure
3. Blood viscosity
4. Pumping effect of the intermittently contracting muscle on vessels & venous valves  muscle perfusion

H: To describe utero-placental circulation

See fetal/maternal section
VII: APPLIED ASPECTS OF CVS PHYSIOLOGY
A: To describe responses to changes in posture
Effects of steep head down tilt/trendelenberg position 2
Affects of lying down from a standing position 2
Postural hypotension - BP, dizziness, dimness of vision & fainting
Sympathetic vasoconstrictor fibres are important in compensating for gravitational effects. People on sympatholytic
drugs or in diabetes where there is damage to this system or with primary autonomic failure are more prone to
orthostatic hypotension.

G-force
+ve g (force from head to foot) – at 5 g a person blackouts due to VR. This can be prevented by antigravity suits
that compresses the abdomen & legs to decrease venous pooling & aid VR.
A body can tolerate g-force much better across the body (chest to back) & astronauts are positioned this way to
allow them to reach escape velocity without ill effects.

On arising from the horizontal position, in a normal gravitational field, a series of

94B4 reflex adjustments follows which results in a redistribution of blood volume and body 54%
water. DISCUSS the physics and physiology involved.
05A14 Describe the compensatory mechanisms in a fit person moving from the supine to the
 56% 63%
03A12 99B6 standing position. Explain mechanisms that maintain cerebral blood flow on moving
51% 60%
98B2 96B4 from a supine to a standing position. 5

Gravitational effects
The circulatory system acts as a hydrostatic column of fluid subject to the effects of gravity (all pressure curves are
taken at the level of the heart). The pressure in any vessel below the heart is increased & any vessel above the heart
is decreased by the effect of gravity when standing.
This difference is 0.77mmHg/cm. E.g. heart=100mmHg, head=78mmHg, foot=180mmHg.
Gravitational effects are more marked with low circulating blood volume.

From supine to erect…

1. Brain – MAP at head level = ~78mmHg (IMMEDIATE change)
If the level of brain is 30cm vertically above heart level, then the MAP of the brain is 30cmH2O (30x3/4=22mmHg)
lower than pressure at root of aorta.
2. Feet - MAP at feet level is ~ 180-200mmHg. (GRADUAL change, equilibrium does not reach until 1 min)

On Standing 300-800mLs of blood (40% CO) pools in the venous capacitance vessels of the lower extremities
VR + CO MAP. Cerebral ischaemia develops if cerebral flow <60% of flow in the recumbent position. Loss
of conciousness would normally ensue on standing if there were not any compensatory cardiovascular changes…
1. BP stimulates baroreceptors in the carotid sinus & aortic arch  SNS & PNS activity.
Overall TPR increases by 25%: Peripheral vasoconstriction  SVR  ABP.
Peripheral venoconstriction (lesser extent)  VR and CO
Heart:  HR &  contractility
2. Activtion of RAS:
3. ICP pressure falls  cerebral flow & accumulation of metabolites  autoregulatory vasodilation. As
both arterial & venous pressure decrease the drop in flow is less dramatic than if only arterial pressure dropped.
4. Prolonged standing  interstitial fluid accumulation in the extremeties. If the person moves the muscle pump
aids venous return, otherwise they are liable to faint.
5. Venous valves help prevent venous pooling by ensuring unidirectional flow towards the heart with the muscle
pump, and reducing the maximum hydrostatic pressure to below 30 mmHg in the feet.
6. Hormonal mechanisms
SNS activity to kidney  activation of RAS  renin, anigotensin & aldosterone.
Aldosterone Na+ and water reabsorption intravascular volume and thus the tendency for venous
return. Angiotensin II  arteriolar constriction.
 stretch of low pressure baroreceptors  ADH release   water retention
 ANP   sodium natriuresis
Upon standing, there is a fall in CBF due to the effect of gravity on the blood perfusing the brain.
Hydrostatic effect - the brain is now ~30 cm higher than the heart, so the pressure at the top of a column of blood
entering the brain is ~ 23 mmHg lower (ie 30 x 0.76) than that leaving the heart. MAP at brain level  68mmHg.
Gravity increases venous pooling in the deep veins of the legs tendency for venous return & CO.
Decreased CO also decreases CPP.

Mechanisms that maintain cerebral blood flow

Limit cerebral perfusion drop to 20%  O2 extraction increases
The compensatory mechanisms are temporary.

Cerebral blood flow (CBF) is directly related to the cerebral perfusion pressure (CPP) where:
CBF = CPP / cerebral vascular resistance (CVR).
CPP = MAP - ICP or CbVP (whichever is greater).

ICP & Munroe-Kellie doctrine - explains that as the skull is a rigid vault of fixed volume, any attempt to increase
the volume within the skull (eg. due to a space occupying lesion, such as a tumour) will result in a rapid rise in ICP.
A rise in ICP will reduce the CPP and thus CBF

 CPP
MAP – CVS responses described above
ICP or cerebral VP: The CbVP falls by 5-8mmHg (due to gravity) to close to zero, but cannot fall below 0
mmHg (due to collapse of jugular veins) to maintain CPP. falls in MAP lead directly to falls in CPP.

 cerebral vascular resistance

Metabolic autoregulation: Vasodilator metabolites (POOHTALK)  relaxation of arterioles & precapillary
sphincters  vessels dilation  blood flow  washing away of vasodilatory substances. Important for moment to
moment regulation of regional CBF (rather than global CBF).
Pressure autoregulation: Myogenic theory of autoregulation –maintains constant CBF despite changes in MAP
from  50-150mmHg. pressure  stretch on vessel walls & vascular smooth muscle responds by dilating 
tone  radius + resistance  return to normal blood flow despite decreased pressure. Occurs within seconds.

Elderly - susceptible to postural hypotension because sympathetic response is slower and less effective & cerebral
autoregulation does not have an immediate onset.

Prolonged standing in hot weather  blood pooling in lower extremeties and absent of muscle pump  VR. Heat 
venodilation (sometimes sufficient to render venous valves partly incompetent & coupled with small role of
baroreceptor in venoconstriction) VR  CO and cerebral perfusion  faint and collapse
B: To account for CVS changes in haemorrhage & hypovolameia
CVS effects of haemorrhage 6 - 15%BV, 1/3BV 2

CVS response to loss 20% blood volume Acute haemorrage  CO & BP

Compensatory processes occur to…

1. Minimise change in effective blood volume & maintain CO
Venoconstriction & mobilisation of reservoir volumes
Transfer of ISF  plasma 1000mL/hr can be transferred.
renal blood flow  urine volume
Restlessness to muscle pump activity

2. Maintain arterial BP – peripheral vasoconstriction & tachycardia

Cardiac output is redistributed to preferentially maintain cerebral blood flow (carotid sinus reflex, pressure +
metabolic autoregualtion). Peripheral vasoconstriction to the muscles & kidneys occurs. The latter is important as
normally 25% CO goes to the kidneys, which is far in excess of their flow required for tissue oxygenation. Moreover
the oliguria decreases fluid loss.

Detected by high pressure baroreceptors in the carotid sinus  reflex SNS activity to maintain BP - HR +
contractility and veno+vasoconstriction.
Detected by low pressure volume receptors in the right atrium & great veins (respond to 7-10% change)
ADH
Both SNS activityRAS activity & salt + water retention and thrist.

Temporal response to haemorrhage

Delayed responses to restore…
1.Plasma volume – returns to normal by 12-72hrs
2. Plasma proteins – few days
3. RBC – EPO levels 2 renal hypoxia erythropoiesis. Reticulocytes peak at 10days & RBC levels will be fully
restored by 4-8weeks.

02A1 Explain briefly how oxygenation of organs can be maintained during isovolaemic 45%
96B5 haemodilution. 66%

Oxygen supply to organs is dependent upon the oxygen carrying capacity of blood and the delivery of blood to the
organ (cardiac output and regional fraction there of). Together this is termed oxygen flux.

Isovolaemic haemodilution refers to a reduction of the blood's oxygen carrying capacity without a change in blood
volume, such as occurs after a haemorrhage with replacement of blood volume by a crystalloid or colloid fluid. It
results because of the decrease in haemoglobin concentration.

Organ oxygen supply is maintained through:

1. Increased cardiac output (CO)
2. Increased tissue oxygen extraction

The oxygen flux equation describes the amount of oxygen (mL O2 / dL blood volume) delivered to tissues per unit
time (mL/dL/min).
Oxygen flux = CO x (1.34 x [Hb] x SaO2 + 0.003 x paO2)

[Hb] is haemoglobin concentration (g/dL)

SaO2 is oxygen saturation (%)
1.34 is the amount of O2 bound to Hb (mL/g/dL)
0.003 is the amount of O2 dissolved in blood (mL/dL/mmHg)
CO is cardiac output (dL/min)
paO2 is O2 tension (mmHg)

Normal oxygen flux at rest is ~ 20 mL/dL/min.

Isovolaemic haemodilution leads to a decrease in [Hb]. Without a significant increase in either SaO2 or paO2 (not
possible in the standard state at sea level and room air), the only way to return oxygen flux to normal is through an
increase in CO.

CO is a product of heart rate (HR) and stroke volume (SV), and is dependent upon preload, afterload and myocardial
contractility.

Increased CO occurs through several factors:

1. Decreased blood viscosity  an increased tendency for venous return (VR)  SV and thus CO.

2. Decreased blood viscosity  SVR and afterload   CO. Poiseuille's law shows resistance in a vessel is
directly related to viscosity (and length, and inversely related to radius to the fourth power).

3. Metabolic Autoregulation - Local tissue factors (POOHTALK) lead to vasodilation in order to increase regional
blood flow and restore oxygen delivery to normal. Increased regional blood flow tendency for VR  CO. Any
small decrease in systemic blood pressure (BP) due to the subsequent fall in SVR as regional circulations vasodilate,
is quickly detected by the carotid and aortic baroreceptors, leading to an increased sympathetic outflow and thus
increased HR, SV and subsequently CO.

Increased tissue O2 extraction: Local factors independent of the increase in CO also assist in maintaining tissue
oxygen supply despite a fall in oxygen flux. These adaptions occur to increase the oxygen extraction by tissues.
An important mediator of this is a right-ward shift in the oxyhaemoglobin dissociation curve, increasing the p50
(normal 26.6 mmHg) and thus assisting the offloading of oxygen from Hb. Also, the lower pO2 places the tissues on
a steeper position of the oxyHb dissociation curve, further facilitating oxygen unloading as greater amounts of O2
are off-loaded per unit drop in pO2.
C: To explain CVS effects & responses in different forms of shock
Shock – systemic hypoperfusion resulting from reduction in CO or effective circulating blood volume. This results
in hypotension, impaired tissue perfusion and cellular hypoxia.
It is the final common pathway for many lethal events and is grouped into 3 major categories.
1. Cardiogenic - 75% mortality
2. Hypovolaemic - 10-20% mortality
3. Septic - 75% mortality
Rare causes include…
Anaphylactic  systemic vasodilation & increased vascular permiability
Neurogenic  loss of vascular tone & peripheral pooling.

Clinical correlation
Shock evolves through 3 phases…
1. Nonprogressive phase – reflex compensatory pathways (tachycardia, peripheral vasoconstriction & renal
conservation of fluid) are activated to maintain perfusion of vital organs.
2. Progressive stage – tissue hypoperfusion & metabolic imbalances (e.g. acidosis 2 anaerobic
glycolysis/renal failure). Acidosis blunts the vasomotor response  dilation & blood pooling in the
microcirculation  worsening CO, hypoxia & DIC. Arrhytmias.
3. Irreversible stage “refractory shock”– cellular & tissue injury is so severe that, even after correction of
haemodynamic defects, survival is not possible. E.g. severe cerebral ischaemia  depression of vasomotor
& cardiac areas of the brain  vasodilation & HR which worsens cerebral ischemia & the cycle
continues. E.g. Coronary hypoperfusion  worsening myocardial failure & worsening of shock & acidosis
 worsening myocardial depression.

Decompensating processes
Ischaemic CNS response  massive SNS stimulation from ischaemic medulla in attempt to maintain cerebral
perfusion at the expense of the rest of the body.

Generalised vasoconstriction – except in the heart & brain

Venoconstriction – increased VR & shifting of blood from splanchnic, subcutaneous & pulmonary reservoirs to the
systemic circulation
Kidney – afferent & efferent (greater) arteriolar constriction. Marked Na+ retention. ATN often occurs.
Adrenal medulla – increased circulating NA leads to stimulation of the reticular formation & restlessness.
Chemoreceptors – anaemia, hypoxia & acidosis stimulates chemoreceptor afferents  vasoconstrictor discharge &
respiratory stimulation.
Angiotensin II – thirst & BP rise, aldosterone & vasopressin  Na & water retention
Capillaries – reduced capillary pressure means interstitial fluid moves into the capillaries along most of their course,
helping to maintain the circulating blood volume.
D: To explain CVS responses in pregnancy, exercise, cardiac failure, IPPV, anaesthesia, PEEP & the valsalva
manoeuvre
 Cardiac failure
Cardiac failure - reduction in cardiac function renders the heart unable to maintain sufficient cardiac output to
supply the metabolic demands of the tissues & organs of the body and compensating mechanisms have occurred.

Most is due to impaired contractile function (systolic dysfunction) e.g. heart muscle disease (ischaemic injury,
cardiomyopathy), pressure (aortic stenosis, hypertension) or volume (mitral regurgitation, fluid overload) overload,
or dilated cardiomyopathy. Mechanical pumping (contractility) & ejection fraction are reduced. Inadequate HR-
heart block, post MI.
Diastolic dysfunction occurs when the heart cannot adequately relax  ejection fraction &  cardiac output. E.g.
Massive left ventricular hypertrophy, restricted filling (constrictive pericarditis, tamponade, restrictive
cardiomyopathy),

Regardless of the mechanism CHF is classified as decreased output (forward failure) or blood pooling in the venous
system (backward failure), or both.

Left sided HF  pulmonary congestion and oedema

Decreased renal perfusion  salt and water retention
Decreased CNS perfusion  hypoxic encephalopathy ranging from irritability to coma.

Right sided HF
Usually a consequence of left sided failure. Pure RHF may be caused by intrinsic disease of the lungs or pulmonary
vasculature causing functional right ventricular outflow obstruction or pulmonary/tricuspid valvular disease.
Portal, systemic and dependent peripheral congestion and oedema and effusions
Hepatomegaly with centrilobular congestion and atrophy of central hepatocytes  nutmeg liver. With severe
hypoxia centrilobular necrosis can occur, and with right sided pressure, sinusoidal rupture causes central
hemorrhagic necrosis.
Congestive splenomegaly, sinusoidal hemorrhages and fibrosis
Renal congestion

Compensatory changes of the heart in CHF

Myocardial hypertrophy  ischaemic changes, impairment of diastolic filling & cardiac remodeling.
Blood volume expansion by Na and H2O retention
Tachycardia

Why does a patient with heart failure have limited exercise capacity?
Increased oxygen requirements are placed on the body during exercise. A failing heart is unable to meet normal
metabolic demands, let alone increased demands during exercise, hence limited capacity. The oxygen that is
available will be preferentially given to tissues that require it.
Oedematous lungs – decreased alveolar perfusion and less oxygen entering adds to effect.
Endothelium-dependent vasodilation in peripheral blood vessels is impaired and may be one mechanism of exercise
limitation. Relates to abnormal release of NO (vasodilator) & endothelin (vasoconstrictor). Hypoxia,
catecholamines, angiotensin II & sheer stress  endothelin (mainly from pulmonary vascular bed).
 CVS effects of IPPV 5 & PEEP 2

01B1 98A1 55% 38%

Explain the effects of intermittent positive pressure ventilation on left ventricular output.
96B3 31%

Intermittent positive pressure ventilation - involves the intermittent flow of gas by the generation of positive
airway pressures in order to overcome pulmonary elastance and airway resistance. IPPV essentially reverses
intrapleural pressure (negative with spontaneous ventilation; zero or positive with IPPV) and alveolar pressure
(atmospheric with spontaneous ventilation; positive with IPPV).

On inspiration – active process

 Initial SV as blood is forced from the pulmonary vasculature into the left atrium LVEDV and thus preload
CO. Also  LV afterload as the increased intrathoracic pressure increases the gradient from the LV to the
abdominal aorta.

 Followed by SV as the increased intrathoracic pressure VR (RAP reduces pressure gradient favouring
VR)  RV preload.
RV afterload due to increased intraalveolar pressure & sometimes large lung volume   pulmonary
vascular resistance (collapses intra-alveolar vessels)  RV output  LV preload  CO.
LV preload also due to external splinting (due to higher intrathoracic pressures) and left-shifting of the
interventricular septum reducing left ventricular volume.
LV afterload due to increased pressure gradient from thorax to abdomen.
HR increases in response in order to maintain CO.

On expiration – passive process

 Initial SV as the decreased intrathoracic pressure and increased pulmonary vascular compliance allow pooling
of blood in the pulmonary vasculature, reducing left atrial filling, decreasing LV preload.

 Followed by a relative LV output as the now decreased intrathoracic pressure allows greater return to the left
ventricle. This effect is less than that for spontaneous breathing where end-expiratory intrapleural pressure is ~
-3cmH2O. With IPPV IPP falls to atmospheric (ie. 0cmH2O) if there is no PEEP.
HR falls in response to sudden increased BP from increased CO with improved venous return.

Overall CO. Decreased CO due to poor systemic venous return is more marked with hypovolaemia, PEEP and
high mean airway pressures.
Benefit in cardiac failure, largely due to decreased LV afterload, decreasing cardiac work. May decrease
sympathetic tone as pathaological factors leading to sympathetic activation are corrected.
  Valsalva manoeuvre 8
Explain the cardiovascular responses to a Valsalva manoeuvre maintained for 30 seconds. What
94B2
can be learnt about cardiovascular function from observing these responses?

Valsalva manoeuvre - originally described in 1704 as a method for expelling pus from the middle ear. Performed
by blowing a mercury column to 40mmHg and keep it there for 10 seconds (forced expiration against a closed
glottis after a full inspiration). Defining feature of the manoeuvre is the increased intrathoracic pressure

Major effects: Cardiorespiratory system

Phase 1: Small BP briefly after onset of
straining. Pulse steady during this period.
Due to intrathoracic pressure squeezing
intrapulmonary vessels  return to L heart
(increased preload)  SV(due to Starling’s
law) and blood pressure rises slightly for a few
beats. Increased pressure also transmitted to
the aorta – 2nd reason for the rise.

Phase 2: BP due to decreased tendency for

VR and consequent decreased CO.
Baroreceptors sense this fall and reflex
compensatory mechanisms  HR and
vasoconstriction, raising the blood pressure
towards normal.

Phase 3: BP dips for several beats after the

release of straining. Reverse of Phase 1
mechanism – i.e. squeeze on intrapulmonary
vessels removed and they increase in calibre.
Return of blood to the left heart transiently
reduced.

Phase 4: Overshoot as compensatory

mechanisms (vasoconstricted peripheral
vasculature) continue to operate with restored
venous return. The increased blood pressure
causes a bradycardia via the baroreceptor
response. Peripheral vascular relaxation returns blood pressure to normal.

Valsalva ratio - calculated by dividing the longest R-R interval during phase 4 by the shortest R-R interval during
phase 2 (or dividing the maximum heart rate during phase 2 by the minimum heart rate during phase 4).
Normally > 1.5. A decreased ratio is seen with increasing age as there is decreased baroreceptor responsiveness and
consequently less heart rate changes.

Uses of the Valsalva manoeuvre

1. As a bedside test of autonomic function. 
2. Rversion of supraventricular tachycardia (because on increased vagal tone during phase IV)
3. An aid in the assessment of some heart murmurs - HOCM / MV prolapse increase, all others decrease.
Arterial blood pressure response and Korotkoff's sounds during Valsalva's manoeuvre.
A: Sinusoidal response in normal patient.
B: Absent overshoot in patient with autonomic dysfunction (e.g. autonomic neuropathy and drugs) - the BP
falls and remains low until the intrathoracic pressure is released.  Changes in pulse rate and overshoot are absent. 
C: Square wave response in patient with heart failure, constrictive pericarditis, cardiac tamponade and
valvular heart disease when CVP is markedly raised - BP rises and remains high throughout the manoeuvre and
returns to its previous level at the end.

Patients with primary hyperaldosteronism also fail to show the heart rate changes and the blood pressure rise when
the intrathoracic pressure returns to normal.  Unknown why this fails to occur. Their response to the Valsalva
manoeuvre returns to normal after removal of the aldosterone-secreting tumour.
E: To explain CVS changes in ageing
Ageing – decreased viability or increased vulnerability to stress with decreased ability to maintain homeostasis.
Middle aged – 45-59 years
Elderly – 60-74 years
Old aged – 75-89 years
Very old – 90+ years

Causes – unknown, possibly related to alteration in DNA, programmed cell death, wear & tear, accumulation of
substances in tissues (collagen, amyloid, calcium), reduction of endocrine & immune function.

Neural – postural control is impaired & is associated with slower reflexes. Autonomic regulation of CVS functions
& maintanence of body temperature are impaired.
CVS changes with ageing 2 Either due to the aging process, prolonged deconditioning or age related disease.
Maximal HR – resting HR unaltered, but maximum HR decreases from 200 to 160 bpm.
Intrinsic HR – without autonomic influence is reduced.
supraventricular arrythmias & ventricular ectopics - fibruous infiltration of the SA node & loss of pacemaker
cells. Loss of some L ventricular perkinje fibres.
connective tissue – collagen replaces fragmented elastin. Deposits of amyloid & lipofuscin occur within &
between myocardial cells.
myocardial wall thickness – secondary to impedence to LV output
compliance – secondary to fibrosis of endocardium
Valvular incompetence - 2 to calcification
maximal SV
maximal exercise performance – due to maximal HR+SV. Often related to deconditioning or age related
disease, as healthy elderly patients can CO by the Frank-Starling mechanism. There is no significant CO declined
in healthy patients from 25-79yrs.
MAP & SBP – due to large artery elasticity & stiffening of arterial vasculature.
DBP – due to peripheral resistance
DBP > 75-80yrs – due to rapid run off of blood in stiff large arteries
pulmonary artery systolic pressure – 20mmHg (20yrs) to 26mmHg
pulmonary artery diastolic pressure – 9 to 11mmHg
pulmonary vascular resistance – 70-120 dyn x sec / cm5
Imparied baroreceptor mechanism  postural hypotension
responsiveness of -adrenergic agonists – either receptors, affinity or generation of cAMP
VIII: MEASUREMENT OF CVS FUNCTION
A: To outline the physics of blood flow
Vascular resistance vs. impedence 2
Resistance in fluid systems

Medical physics of pressure/flow/resistance

Flow = pressure/resistance (blood flow can be measured by Doppler flow meters)
The effective perfusion pressure = intraluminal pressure at the arterial end – mean pressure at the venous end.
Resistance is expressed in R units = pressure (mmHg) / flow (mL/s).
Flow varies directly & resistance inversely with the 4 th power of the radius small arteriolar caliber changes have a
pronounced affect on systemic arterial pressure.

Reynolds equation.

In vessels the thin layer of blood next to the wall does not flow.
The next layer has a low velocity, the next slightly higher until
the center of the stream which has the highest.
Laminar flow = streamline flow in straight blood vessels, which
occurs up to a certain critical velocity after which flow becomes
turbulent. Turbulance is also related to vessel diameter & blood
viscosity. Constriction  turbulence. viscosity  turbulence
(e.g. anaemia).
Velocity = flow/area if flow is constant velocity increases to
any decrease in area of the vessel. Velocity of blood is inversely
proportional to the total cross-sectional area at that point.
velocity is highest in the aorta, & lowest in the capillaries.

Viscosity – plasma is x1.8 and whole blood x3-4 as viscous as

water. majority depends on haematocrit. The high viscosity
has less effect in small, than in large vessels haematocrit
only has effect on peripheral resistance when the change is
large e.g. severe polycythemia or anaemia.

Laplace’s law in relation to blood vessels & heart

Pressure = Tension/radius
The smaller the radius of a blood vessel, the lower is the
necessary wall tension to balance the pressure. E.g. capillaries
= 16dynes/cm, aorta = 170,000dynes/cm, vena cava =
21,000dynes/cm. Dilated hearts are at a disadvantage because
their dilated radius means a greater tension (more work)
must be developed to produce any given pressure.

B: To give a detailed account of the various methods of

measuring blood pressure
See measurement section

C: To explain the various methods of measuring CO & their limitations

See measurement section
B: To outline methods & principles used to measure regional blood flow

Blood volume & its regulation

Zero reference point in the circulation
Response to Aorta cross clamp
Effects of releasing a tourniquet 2
Response to sudden vasodilation
Origins of arterial blood pressure
Morbid obesity