Physiology Cardiology RCR1

The Cardiac Cycle

 Heart sounds are traditionally heard a ‘lub-

dub’
o Lub = first heart sound and is the
closure of the atrioventricular valves
o Dub = second heart sound and is the
closure of the semi lunar valves
o Ventricular systole is the time between
the first and second heart sounds
o Atrial systole is mid ‘P’ wave to the first
heart sound
 Electrocardiogram, PQRST
o P wave is the electrical events
associated with atrial systole
o QRS complex are electrical events associated with ventricular
systole
o The first positive wave is the R wave
o A negative wave preceding the R wave is the Q wave and the
negative after is an S wave
o The T wave is electrical events associated with ventricular
repolarisation or recovery
o Q is usually small but if large then indicates a full thickness MI
 LEFT VENTRICULAR PRESSURE
A. Surge of pressure when atria contract and top up the ventricle, the
increase in ventricular volume this produces is quite small and the
atria aren’t responsible for all ventricular filling
B. Ventricular systole starts, increased pressure causes closure of the
AV valves (first heart sound), at this time all the valves are closed
and there is isovolumic contraction while the ventricular pressure
rises but the ventricular volume is constant
C. LVP>aortic pressure, therefore the aortic valve opens and there is
rapid emptying of the ventricle
D. LBP = aortic pressure, there is almost a balance between
contraction of the ventricular muscle and the elastic stretch of the
aorta, the rate of emptying is reduced
E. Decrease in pressure in the relaxing ventricle, VP<aortic BP, and so
the aortic valve closes (second heart sound)
F. LVP<LAP and so the mitral valve opens and the ventricles starts to
fill again
G. As LV fills the LVP increases once more
H. The next atrial contraction beings
 AORTIC PRESSURE
A & B. Aorta and large arteries are gradually empting as blood slows from
arteries to tissues to veins, relaxing the elastic stretch in the walls
of the arteries and so the aortic BP gradually falls
 C. Aortic valve opens and when ventricular pressure exceeds aortic
pressure (at roughly 80mmHg), aortic BP increases to peak at
systolic BP of 120mmHG
D & E. Diastole starts – ventricles relax – blood starts to flow from aorta
to ventricle but this closes the aortic valve, the dicrotic notch on
the aortic pressure wave is a small pump in aortic pressure as the
valve closes and is associated with a temporary fall in aortic blood
flow
F & G. Elastic recoil of the arteries drive blood through the tissues, BP
gradually falls to a minimum of diastolic BP of 80mmHg
 VENTRICULAR VOLUME
A. Atria top up ventricles (by 5-20%) to end diastolic volume
(normally by 120ml)
B. Constant volume even though ventricular systole starts
C. Rapid Ejection
D. Slow ejection down to end systolic volume (normally 50ml of
normal SV is about 70 ml and normal ejection fraction is 60%
E. Constant volume (valves closed)
F. Mitral valve opens –rapid filling, initial surge of blood with built up
in atria during ventricular systole
G. Slow filling or diastasis veins into atria into the ventricle, this
period is shortened when HR increased to about 180bpm, at rates
faster than the period of F shorted and SV falls
H. Next atrial contraction
 3rd heart sound is due to rapid ventricular filling and is said to be
analogous to the sound produced by a sail flapping in the wind, this is
common in athletes with slow HRs
 4th HS is due to atrial systole, it is heard when hypertrophy of the LA
pumps into a stiffened LB as occurring in ischaemia heart disease and
hypertension
 Atrial pulse
o A wave is atrial systole
o C wave is AV valve closing and cusps of the valve bulging into the
atria
o V wave is during ventricular systole, atria fill with blood (venous
return) and when the AV node opens, blood surges into ventricles
and atrial pressures fall
o IN PHASE G venous return continues and fills atria and ventricles
o X descent is a fall in pressure following the c wave
o Y descend is a fall in pressure following the v wave
o Venous pulse is the same course as this

Cardiac Muscle and Cardiac Action Potential

 Cardiac muscle show some properties of skeletal muscle and smooth

muscle
o It is striated like skeletal, the fibres are branched and connected
electrically by intercalated discs and its activity is myogenic
 In cardiac muscle, every fibre contracts each time the heat beats so it is
not possible to alter the strength of contraction by altering recruitment,
the heart beast rhythmically and so AP frequency will not control the HR<
in the heart muscle the strength of contraction is varied by changing the
calcium concentration inside the cardiac cell
o Calcium enters the cell from outside and is
also released from intracellular stores
o Intracellular calcium concentrations are
raised after an AP as calcium enters the cell
from the outside, calcium is released from
quick release intracellular stores, there is a
calcium induced calcium release
o Calcium concentrations are returned to
baseline by active calcium extrusion (ATP
dependent Ca2+ pump), active sodium
calcium exchange on the cell membrane
(due to ATP using sodium pump) and active uptake into the
sarcoplasmic reticulum
 The contractile mechanism is essentially the same as in skeletal muscle,
where actin and myosin filaments pass over each other as cross bridges
are formed and broken, calcium ions bind to Troponin C, which is
attached to tropomyosin, a cross bridge is formed and moves the actin
filament over the myosin filament, the myosin head disengages and the
process repeats, ATP is required to alter configuration of the myosin head

 PHASE 0 = depolarisation caused by sodium influx

 PHASE 1 = initial repolarisation caused by potassium
efflux
 PHASE 2 = plateau phase resulting from calcium influx
 PHASE 3 = repolarisation cause by potassium efflux
 PHASE 4 = resting potential as sodium channels are
reactivated
 SAN – sloping resting phase gives rise to its
pacemaker activity, activation of SNS to the SAN will
speed up the HR by making this slope steeper,
activation of the PNS makes the slow flatter and hence
will slow heart rate down
 AVN – shape is similar to that of the SAN, except the
slow in phase 4 is less due to the absence of a type of
sodium channel, this contributes to the delay at the AV
node and gives time for atrial contraction to top up the
ventricle
 Purkinje Cell – long plateau phase in AP means it is not
possible for cardiac muscle to enter into tectonic
contraction, as the twitch of the muscle contraction is
over before the muscle cell is ready to depolarise again so the heart is
forced to beat rhythmically
 Positive inotropes include beta agonists (speed up calcium uptake into
intracellular stores and thus increase availability) and cardiac glycosides
 (inhibit sodium and potassium ATPase, increase intracellular sodium and
thus decrease sodium/calcium exchange and increase intracellular
calcium)
 Negative inotropes include calcium channel blockers and beta blockers

Extras to Taking Blood Pressures

 Arterial blood pressure, occurs in body at bifurcation of the carotid artery,

swelling is the carotid sinus, that has stretch receptors for BP, the sinus
nerve give information to the brain which will instil PNS and decrease HR,
force and will cause vasodilation
 Systolic = 120mmHg, pulse pressure, affected by SV
 Diastolic = 80mmHs, effected mainly by peripheral blood flow and
increase aortic pressure
 High BP can lead to stroke and heart attack
 Take BP at brachial artery, cuff increase pressure until greater than in
brachial artery, no flow or pulse, decrease pressure, first sounds is when
pressure slightly lower than in the artery causing turbulent flow
downstream, tapping sound, gets louder, quieter, muffles and then
disappears, once no tapping then this is lamina flow
 THEY ARE THE KAROTKOPF sounds
 Record to the nearest 2mmHg
 MISTAKES  ensure seated, feet on found, back supported, check both
arms, roll up sleeve, but ensure sleeve does not cause a cuff also, have
bladder on the front, tubing at the top, cuff should be reasonably tight but
so you can fit 2-3 fingers underneath, ears point forward and use
diaphragm side, pump up to 160-180mmHg and let it fall at 2mmHG per
second

Venous Return and Cardiac Output

 Preload  factors which determine the ventricular filling can be

described as determining the preload of the ventricle, the right atrial
pressure can be taken as a measure of the preload of the right ventricle
o Left atrial pressure can be taken as the preload to the LV but this is
difficult to measure so often the pulmonary artery wedge pressure
is used to estimate of the left ventricular end diastolic pressure is
measured using an arterial catheter passed into the LV
 FACTORS THAT CONTRIBUTE TO PRELOAD
o Gravity  in upright position, this is a positive factor for organs
above the heart but negative for tissues below, the decreased
venous return on standing contributes to postural hypotension
especially if blood volume is low or ANS function is supresses, in
supine position venous return is increased and so this can lead to
lung orthopnoea
o Thoracic Pump  on inspiration the diaphragm flattens,
abdominal pressure is raised, thoracic pressure falls and blood
moves from the abdomen into the thoracic and pools in the legs, on
expiration the diaphragm is domes and so blood moves from the
 legs into the abdomen, this is activity related and ∆ venous return
increases with increased activity
o Muscle Pump  large veins pass between muscle blocks,
especially in the limbs, the veins are compressed when the muscle
contracts, the veins have one way valves so the blood can only
move towards the heart, the pump is too activity related
o Co-localisation  veins are bound together with arteries and
nerves in tight VT sheaths, so as the artery pulsates the vein is
massaged, causing blood to move towards the heart
o Venomotor tone  the great veins have some smooth muscle
within their walls, and this has similar pharmacology as in
arterioles that is will contract when alpha 1 receptors are
stimulated, and hence will increase central venous pressure and ∆
preload
o Blood volume  the great veins act as capacitance vessels for the
storage of blood, increase blood volume results in increased
central venous pressure and increased preload, therefore after a
haemorrhage there will be a decreased preload
 Venous return and CO – in some circumstances an increase venous turn
can produce an increased CO but there are many factors that control CO,
however if CO increases there must be an increase in venous return
 CO = HR X SV (roughly 5l/min, if SV=70ml and HR=70bpm)
 Filling ventricle of 120ml and emptying down to 50ml ∆ the ejection
fraction is roughly 60%
 FICK PRINCIPLE = In a closed system at equilibrium, if a substance X is
neither synthesised or broken down, then the rate at which C enters the
system must equal the rate at which it leaves (eg oxygen in closed system
of lungs)
o Oxygen uptake can be measured by collecting expired air and
measuring the oxygen concentration
o Pulmonary arterial blood oxygen content is measured in a sample
of RA blood from a catheter in the vein into the RRA
o Pulmonary venous oxygen content is obtained by measuring
oxygen content of blood in any systemic artery
o Blood oxygen content is determined by measuring Hb
concentration and oxygen saturation
 Oxygen uptake is 250ml/min, O2 sats are 100%, Hb conc is 150g/l,
arterial oxygen content is 200ml/l, mixed venous sats are 75%
o Mixed venous blood oxygen content is 0.75x150x1.33 = 150ml/l
o Each L picks up 50ml of oxygen
o Therefore lung blood flow is 250/50 = 5l/min
 CO can also be assessed using other imaging systems such as Doppler flow
 ROLE OF HEART RATE – SNS increases HR and PNS slows it, natural rate
of SAN is 100 bpm, at rest heart is under tonic vagal PNS inhibition, HR is
varied by PNS from 100bpm to 70bpm, an increase above 100 required
the SNS
o Maximum effective HR is 180 where above this the ventricular
filling time is so quick that SV falls rapidly
 o Also at high HR there is risk of cardiac ischaemia as diastole time is
shorter (time when coronary supply gets blood)
o HR increases with RAP increases, hence HR increases on
inspiration and falls on expiration
 SV – can be increased by filling the ventricle more or by emptying it more,
the effect of increasing ventricular filling = STARLING
o Starlings Law is that work done by the heart in systole is related to
the resting length of the ventricular muscle fibres
o Increased force of contraction produced by stretching the muscle
fibres is thought to result from the actin and myosin strands being
drawn closer together
o If the muscle fibres are too stretched however, DE compensation
occurs
o The law implies that an increase in venous return will increase CO
 Contractility  stimulation of SNS is said to increase contractility
(sympathomimetics = positive inotropes), an increase in contractility is
an increase in the force of contraction, an increase in intracellular calcium
concentration is what causes an increase in contractility
 Ventricular Failure = contractility of ventricle may be decreased due to
ischaemia, acidosis or death of the muscle fibres
 Heart failures is defined as the inability to maintain a normal CO at
normal filling pressures
 In exercise venous return increases if the exercise is isotonic, cardiac
filling is thus increased, contractility is increased due to SNS, HR increases
and maximum CO is now 25l/min

Renin-Angiotensin System

 The RAS regulates blood pressure and blood

volume, Its effects are mediated by
angiotensin II
 Angiotensinogen is a physiologically inactive
precursor protein (453 AA), constitutively
secreted by the liver, can be altered by
hormones such as oestrogen, hence increase
BP with the pill, AA sequence contains both
sequences of Ang I (10AA) and Ang II (8AA)
 Renin I an enzyme secreted by the kidney,
secreted by the juxtaglomerular apparatus,
stimulated in response to BP and SNS, the release is the primary
determinate of RAS activity, renin cleaves angiotensinogen to make
angiotensin I (which has no physiological activity
 ACE or angiotensin converting enzyme is a peptidase enzyme which is
constitutively expressed by the endothelium of the lung, it converts
inactive Ang I into the active Ang II by cleaving off 2 AA, it will also cleave
other peptides for example vasodilator bradykinin
 Angiotensin II is the active component of RAS, it is a peptide hormone
which promotes vasoconstriction and salt and water retention, affecting
blood pressure and blood volume, it acts on
 o Vascular SM – vasoconstriction
o The adrenal cortex – aldosterone release
o SNS – increased release of noradrenaline
o Kidney – promotes sodium retention
 Angiotensin II is broken down by amino peptidases in blood cells and in
peripheral tissues, and these remove the AA from Ang II, some of these
products have some limited activity
o Ang III (ang 2-8) is a vasoconstrictor
o Ang 1-7 is a vasodilator
 Endocrine renin systemic – circulating renin originates mainly in the
kidneys and had physiological actions all round the body
 Paracrine or local renin system, where all components are present in a
tissue, for example in the kidney, heart, blood vessel walls and various
parts of the brain
 Factors that increase renin release
o Low arterial BP – SNS activation via the baroreceptor reflex (B1-
AR), and intra-renal stretch receptors in the juxtaglomerular cells
o Low blood volume – SNS via low pressure receptors in arterial
stretch
o Altered sodium handling – detected by intra-renal mechanisms in
macula densa
 Factors that decrease renin release
o Like most endocrine systems, renin release is controlled via a
negative feedback mechanism
o Raised arterial pressure decreases SNS activation
o Increase blood volume increases afferent arteriole stretch
o Angiotensin II has a negative feedback mechanism
 RAS is controlled by renin release which is controlled by blood pressure,
ACE is constitutively expressed on the lungs and the liver continually
produced angiotensinogen
 AT1 receptors  mitogenic, pro-fibrotic, vasoconstriction and increase
BP
 AT2 receptors  OPPOSITE OF ABOVE
 AT1 receptors are part of the control of BP, vasoconstriction is a direct
action on vascular SM, the release of ASH and endothelin and the
potentiation of the SNS, as well as aldosterone release form the adrenal
cortex
 AT1 receptors are on peripheral nerve endings, they potentiate NA
release, block NA reuptake and increase NA synthesis, other sites of
action include central control mechanisms in the medulla or the brain and
catecholamine release from the adrenal medulla which both increase SNS
activity
 Aldosterone release is regulated by Ang II and high potassium, it
promotes water retention through increasing sodium retention in the
kidney and the gut, increasing ADH secretion and promoting thirst, which
promotes water and sodium retention and potassium excretion
 OTHER ACTIONS OF AT1
o Mitotic – fibroblasts and SM in scarring
 o Hypertrophy – especially of cardiomyocytes
o Pro fibrotic as inhibits collagen break down
o These are all associated with the pathology of HF and chronic
kidney disease
 AT2 Receptors – stimulate vasodilatation, through NO release and
increased bradykinin production, hey increase collagenases and so
dampen fibrosis, it induces apoptosis and decreased growth factor
expression
 Control of BP is due to TPR (vascular tone where resistance = 1/r 4) and
CO which is a product of heart rate and stroke volume
 Ang II action on BP
o Vasculature – fast acting, short term response, direct
vasoconstriction will increase TPR, interaction with SNS and
endothelin release
o Blood volume, slower acting but longer term response, salt and
water retention via direct activation of sodium and stimulation of
aldosterone, increases venous return (preload) and ∆ CO
 CLINICAL IMPLICATIONS
 Heart failure – low CO, low BP, falling BP leads to Ang II release, pro-
fibrotic and mitotic effects and so increases cardiac remodelling,
therefore RAS inhibition can prevent cardiac remodelling
 Chronic Kidney disease – promotes mesangial proliferation and
hypertrophy, promotes synthesis of TGF-ß and collagen, is degenerative
process leading to glomerulosclerosis
 BLOCKERS OF RAS
o Beta blockers – block SNS stimulation of renin secretion by B1
receptors
o Renin inhibitors – drugs so exist but not very effective
o ACE inhibitors – block Ang I to Ang II, also inhibit breakdown of
bradykinin which causes a dry cough, widely used in HR as
reduced pre and after load as well as having anti-fibrotic effects –
all end in ‘PRIL’
o Angiotensin receptor antagonists – stop Ang II binding to AT1
receptor, ‘SARTANS’, AT2 are unaffected at this time, no dry cough

The Electrocardiogram

 P wave = first event of the cardiac cycle, it the depolarisation of the SAN, it
spreads from RA to LA, depolarisation generates the P wave, it is a
reflection however not the node itself
 PR interval = depolarisation spreads through the AV node towards the
ventricle, conduction through the AVN is slowed to allow ventricular
filling, this conduction produces the interval, it should be between 0.12
and 0.2 seconds long
 QRS complex = conduction spreads from the AV node down the Bundle of
His and through the Purkinje fibres and up through the epicardium, the
nature of this spread produces the complex
 o Q = negative wave preceding R, caused by depolarisation of
ventricular septum as seen in L pointing leads (I, II AvL, V5 and V6)
o R = an upwards deflection
o S = a deflection below the isoelectric line
 T wave = depolarisation flows from the endocardium to the epicardium,
repolarisation flows in the opposite direction, as in the opposite direction
the T wave is in the same deflection as the QRS complex,
 U waves are small deflections in the same direction as the T wave, their
origin is thought to be the papillary muscles
 ECG = 12 leads
o Bipolar leads
 Lead I is RA to LA
 Lead II is RA to LL
 Lead III is LA to LL
o Unipolar or augmented leads
 Lead AvF – lead I to LL
 Lead AvL – lead II to LA
 Lead AvR – lead III to RA
 Limb leads and augmented leads look at the heart in the vertical plane
while the chest leads look at the horizontal plane
o V1 – 4th intercostal space on R of sternum
o V2 – 4th intercostal space on L of sternum
o V3 – in middle
o V4 – 5th intercostal space in mid-clavicular line
o V5 – 5th intercostal space in anterior axillary line
o V6 – 6th intercostal space in mid-axillary line
 Anterior surface = V1, V2, V3 and V4
 Lateral surface = I, AvL, V5 and V6
 Inferior surface = II, III and AvF
 RHS – AvR and V1
 Reporting on an ECG – NOTE THAT EACH SQUARE IS 0.04s
o Rhythm – rate should be 60-100bpm, is it regular and does each P
wave produce a complex
o Conduction intervals – the ECG is based on the cardiac cycle and so
should reflect the timings, for example the PR interval should be
0.12-0.2 seconds and if this is longer then it suggests heart block
and if shorter then suggests depolarisation originates near the
AVN, depolarisation of the ventricles should be rapid and spread
equally so the QRS should have a single peak and be less than 0.12s
o Cardiac axis – represents the general direction of the
depolarisation of the heart, should start at SAN on top right of
heart and spread to bottom left or the apex, an axis of O would be
one that moves from L to R, it is t be expected to be -30 to 90
o Description of QRS complexes
o Description of St segment and T wave

Vascular Physiology
 Primary function of the CVS is the rapid bulk transport of gases, nutrients
(glucose, AA etc) and water and to wash out metabolic waste products
 Arteries are bigger and have thicker walls to capillaries
 Capillaries have the largest cross sectional area
 Velocity of blood flow is in the capillary beds
 BP falls across the vascular tree
 Wall tension is lower in small vessels than in large ones – wall tension is
highest in the aorta which is prone to aneurism formation and is lowest in
the capillaries (as thin walls and facilitate exchange)
 Blood flow through the circulatory system is 5l of blood, each day your
heart will beat roughly 100,000 times, pumping 7,500 l of blood through
the vascular tree every day, it takes less than 60 seconds for a RBC to
circulate
 What two forces determine rate of blood flow
o PRESSURE DIFFERENCE/GRADIENT – mean arterial blood
pressure
o REGULATION OF BLOOD FLOW TO ORGANS – blood flow =
MABP/TPR, increase in pressure difference, change in resistance
o SIZE OF BLOOD VESSEL
o VISCOSITY OF BLOOD
 Contributions to resistance include the vessel radius and the viscosity of
the blood
o Flow = 1/vessel radius4
o Flow = blood viscosity, greater the viscosity the less the flow
 Blood is viscous due to two parts
o Haematocrit – proportion of blood volume that is occupied by RBC,
expressed as a percentage usually 37-47% in females and 40-54%
in males
o Plasma concentration and type
o Temperature
 There is less haematocrit in the capillaries due to axial accumulation and
plasma skimming
 Small changes in the diameter of blood vessels lead to big changes in flow
 The major function of circulation is to ensure appropriate distribution of
blood flow to organs and tissues to meet their metabolic demands
 Blood flow to most tissues and vascular beds can be regulated in
accordance with the tissue needs
 CO is distributed according to metabolic and functional demand, however
this changes through exercise when there is a 90% CO increase that does
to muscles
 The blood vessels that vary this are called resistance vessels – small
arteries and arterioles (500-100 and <100 um in diameter)
 Factors that determine vascular tone can be intrinsic (local regulation eg
stretch or local chemicals) or extrinsic (systemic regulation eg hormones
and nerves)
 Regulation of vascular myocyte tone – excitation contraction coupling
o Stretch and auto-regulation of blood glow – contributed to basal
tone, stabilises tissue blood flow, well developed in brain, kidney
 and myocardium, pronounced in
haemorrhagic shock
o Regulation by endothelium, vasodilators
include NO, endothelium derived
hyperpolarising factors and prostacyclin,
vasoconstrictors include endothelin
o NO endothelial dysfunction is the NO
pathway, in diabetes, hypertension and
atherosclerosis, used NO
therapeutically, it works on resistance
arteries, arterioles and small veins
o NB BLOOD GOES TO WHERE IT IS
NEEDED
o Metabolic hyperaemia occurs in
seconds, it is caused by hypercapnia,
hypoxia, acidosis, increased
osmolarity, extracellular adenosine,
potassium and phosphate ions
o Autocoids are agents produced by a variety of cells, they act locally,
mainly pathological for example histamine, bradykinin, serotonin
eicosanoids and prostanoids
o Systemic hormones have actions throughout the circulation, for
example adrenaline, Ang II (constrictor), Vasopressin/ADH
(constrictor), ANP (dilators via cGMP), insulin and oestrogens
(dilators)
o Vasoconstrictor nerves are mostly SNS, cause vasoconstriction in
all vascular beds, noradrenaline, on adrenergic alpha-1 receptors,
for tonic activity
o Vasodilator nerves can be sympathetic (eg sweat and skeletal
muscle) and mediated by Ach or parasympathetic (salivary and
gut) mediated by Ach or NANC transmitters, nociceptive C-fibres
mediated by neuropeptides

Microcirculation and Lymphatic’s

 Fluid compartments include intracellular and extracellular (made up of

the intestitum and vascular compartments
o Total body water is 60% of body weight = 42l
o ICF = 40% at 28l and ECF is 20% with 14l (vascular is 3.5l and
interstitial is 10.5l)
o Fluid moves by free water movement of via the exchange barrier
(starlings forces)
 Capillaries can be of three structures
o Sinusoidal or discontinuous – with large lipophobic molecules and
RBC that can move in or out
o Fenestrated - with small lipophobic molecules moving in and out
o Continuous – that has a very slow diffusion rate for large
lipophobic molecules, slow diffusion rate for small lipophobic
molecules exiting by a tight junction and intercellular cleft, and fast
 diffusion for gases, lipophilic molecules, it has infused
invaginations
o A basement membrane and glycocalyx layer is present in all three
 Diffusion is the main mechanism by which substances move from the
blood to the ECM of vice versa, results from thermal motion of water
molecules and dissolved substances in the fluid
o Fick’s law of free diffusion describes the rate of diffusion
 Js = -PAdC
 P is permeability of membrane to given solute
 A is SA available for exchange
 dC is concentration gradient across membrane
o If a substance is lipid soluble it can diffuse directly across the cells
membrane
o If it is water soluble and non-lipid-soluble, they can only diffuse
through intercellular pores, roughly 4nm wide, (0.003% of SA)
o Large solute movement is restricted to a few large pores of 20-
30nm in radius
 Limiting factors include the capillary blood flow and the number of
perfused capillaries
o Capillary blood flow – high permeability substances, a the flow is
limited (if flow rate is raised, the amount of a solute transferred
per unit time is increased), lower permeability, is diffusion limited,
so amount of a solute delivered increased by reducing rate of
blood flow
 HIGH PERMEABILITY – flow limited diffusion
 LOW PERMEABILITY – diffusion limited diffusion
o Capillary number and hence the SA
 Water moves freely due to its small size and presence of sufficient pores
 Starlings principle – hydrostatic pressure (water moves from region of
high pressure to low pressure) ∆ pushes water out of capillary, and
colloid oncotic/osmotic pressure (water moves from area of low protein
concentration to high protein concentration) ∆ pushes water into
capillary
 SUMMARY NOTES – capillary wall is an imperfect semi-permeable
membrane, both solute an water cross the wall by passive transport
(except glucose in brain), solutes diffuse down a concentration gradient,
water flows down a pressure gradient, some solutes are also swept along
in the water in CONVECTIVE transport, there are other transport
mechanisms including pinocytosis and transporters
 Lymphatics and interstitium
o Note the entire plasma volume completes an
extravascular circulation at least once a day
 When capillary filtration rate is higher than lymphatic drainage
it causes oedema, oedema occurs in a number of conditions
 Increased capillary pressure – occurs in RHF,
raised venous pressure, changes the pressure
gradient across the capillary bed to favour
filtration, filtration in capillary beds is not
increased by an increase in systemic arterial
 pressure, if arterial pressure is raised as in hypertension,
there is no significant increase due to auto-regulation
 Decreased plasma proteins – as in nephrotic syndrome,
gross proteinuria, this reduces the oncotic pressure of the
blood, reducing reabsorption and increasing net filtration,
can either be due to a decrease in protein production or an
increase in secretion from kidney
 Reduction in lymphatic drainage – filariasis, if lymphatic
drainage is impaired both fluid and proteins accumulate in
the tissues, producing a dramatic and painful swelling
 Increase capillary permeability
 Inflammatory swelling – rubor (redness), calor (heat), dolor (pain) and
tumor (swelling), due to high protein exudate caused by an increase in
endothelial permeability to water and proteins, increase permeability due
to formation of intercellular gaps in venular endothelium

Control of Blood Pressure

 We need a relatively constant BP – arterial BP is the driving force to

perfuse the tissues with blood, if too low then the brain blood flow falls
and kidney filtration falls, however if too high pathological damage will
occur
o Perfusion (flow) – mean aBP/total peripheral resistance
 Baroreflex for acute regulation of BP
o 3 main elements form the reflex arc
 Afferent (Sensory) elements - baroreceptors
 Central relays – cardiovascular centres
 Efferent (Motor) elements – blood vessels and heart
 A fibres – large diameter, fast conducting, myelinated nerves, low
threshold (30-90mmHg), at normal pressures all are activated
 C fibres – more abundant, narrow, slow conducting, unmyelinated, high
threshold (70-140mmHg), at normal pressures 25% activated, number
activated rises as pressure rises
 Baroreceptors sense rate of rise in pressure (dynamic sensitivity) as well
as the magnitude of pressure (static sensitivity)
 Cardiovascular control centres – medulla is the primary site in the brain
for regulating sympathetic and parasympathetic (vagal) outflow to the
heart and blood vessels
 o Nucleus tractus solitaries of the medulla
receives sensory input from different
systemic and central receptors (chemo and
baro receptors)
o Autonomic outflow from the medulla to the
heart and blood vessels where they
modulate the activity of these target organs
o The hypothalamus and high centre modify
the activity of the medullary centres
 In response to an increase in BP, decreased SNS
and increased vagal activity, decreased SNS means
vasodilation and ∆ reduction of TPR, rapid
decrease in HR and reduce contractility means
reduced CO, this therefore means a fall in MABP
 Postural hypotension or orthostasis is a drop in BP sufficient to cause
inadequate supply of blood to the brain and other organs, you require a
reflex increase in sympathetic tone in order to prevent this, as well as
muscle pumps
 However it is not just controlled by the baroreceptor reflex, although this
is the most important in humans
 Peripheral arterial chemoreceptors, detect low PO2 or high PCO2, and
elicit SNS for vasoconstriction and increase HR, primarily involved in
breathing, but it is resent to protect the brain blood flow when arterial BP
falls, found in carotid and aortic bodies, only role is in sever hypotension
 Cardiopulmonary reflexes are sensory inputs from the heart and lungs,
which minimize aBP changes in response to changes in volume, elicit
tonic (continuous) reduction in HR and peripheral vasoconstriction
 LONG TERM IT IS CONTROLLED BY RAAS
 What factors influence BP?
o Age
o Gender
o Race/ethnicity (commonly seen in African Caribbean)
o Low birth weight
o Low socioeconomic and educational background
o High salt diet
o Obesity
o Excessive alcohol intake
o Stress and anxiety
o Smoking
o Diabetes mellitus

Cardiopulmonary Responses to Exercise

 Dynamic or isotonic exercise – rhythmic contraction/relaxation of muscle

group, endurance and aerobic training, for example walking or jogging
 Static or isometric exercise is continued muscle tension, no movement,
strength or power training, for example resistance or weigh training
 Two types of muscle
 o Type I – slow twitch, dependent on oxidative phosphorylation,
good blood supply, lots of mitochondria and myoglobin, mainly
postural but also used in endurance events
o Type 2a & 2b – fast twitch, relies on creatine phosphate to
regenerate ATP, not so dependent on blood supply or
mitochondria, large amounts of glycolytic enzymes, used in
springing and explosive events, 2a is oxidative (slightly pink) and
2b is glycolytic
 Exercise is important!
 Exercise Intensity can be defined in terms of oxygen uptake, they have a
linear relationship where resting oxygen consumption is 250ml/min,
moderate exercise is 1000ml/min and heavy is 2000ml/min
 ATP is required for muscle contraction, however you only have enough
ATP to power a few twitches, the ATP is regenerated from 3 sources
 Cellular respiration (requiring oxygen)
 Creatine phosphate
 Muscle glycogen
 Creatine phosphate is for short bursts of
energy and can be used to replenish ATP
from ADP
 Glycogen is stored in bulk in muscle and can
be broken down to provide substrates for
glycolysis, it yield 2 ATP and 2 lactic acid
molecules, enough to keep functioning if
oxygen is insufficient, however this source is
limited and eventually the muscle must
depend on cellular respiration
 Cardiopulmonary responses do not precede the onset o exercise and so
oxygen stored are quickly spent in this lag period, cardiopulmonary
adaptations aim to supply oxygen to match demand during the exercise,
but when exercise is over, the initial debt will need to be repaid
 Oxygen debt is incurred in three stages
o Depletion of ATP
o Depletion of creatine phosphate
o Build up of lactic acid and depletion of glycogen
 Oxygen is repaid in three steps as well
o Fast – re-phosphorylation of ATP/creatine
o Slow – lactate conversion back into glucose/glycogen
o Ultraslow – increased metabolic rate after exercise
 Cardiovascular effects of exercise include, increased HR and SV, moderate
increase in MABP, a decrease in TPR and changes in distribution of blood
flow
 HR – increased by SNS and decreased by PNS
 SV – is modulated by preload and contractility (SNS increase of calcium
will increase the force of contraction)
o Preload is determined by gravity (sitting up decreases return from
organs beneath heart), the muscle pump (veins between muscle
are compressed as muscle contracts also remember valves prevent
backflow), venous tone (sympathetic activation causes
 venoconstriction) and blood volume (increase volume will
increase CVP and venous return)
 Total peripheral resistance, is the resistance to blood flow which is
dependent on vascular tone, where vasoconstriction will increase the
resistance and vasodilation will decrease it
o Vasodilation is caused by a increase in metabolism leading to
increased production and accumulation of metabolites that will
produce vasodilation and increase blood flow, these include CO2,
H+, adenosine, K+ and lactate, (also endothelial factors such as No
and prostaglandins (PGI2)
 In exercise both oxygen consumption and carbon dioxide production
increase, therefore respiratory rate and tidal volume must both increase,
these are controlled chemically
o Chemoreceptors – central ones are located in the medulla and look
at the PaCO2 and H+ concentration in the cerebrospinal fluid,
while peripheral ones are in the aortic and carotid bodies and
regulate PaO2 and PaCO2 and H+ in the blood
o Neural input is via the motor cortex, intercostal muscle and
skeletal muscles
o Remember that arterial blood gases to not change greatly during
exercise
 It is unclear what triggers these responses, some believe it is the central
control hypothesis (feedforward hypothesis), where areas in the brain
that drive locomotion also produce the drive for increased respiration
and HR, this is supplemented by feedback sensory input from moving
muscles
 Baroreceptor reflex (is reset in hypertension)
 Usually this keeps blood pressure constant at a set point but
during exercise central command may temporarily alter the
set point, so the effect is that BP is perceived to be too low
and therefore increases the HR
 LIMITATIONS OF EXERCISE
o Delivery of oxygen takes part in 3 areas
 O2 uptake by the lungs
 O2 delivery by the CVS
 O2 extraction by the muscle
 Normally the CVS is the limiting factor, as blood takes a
second to travel to the pulmonary capillaries, gas exchange
here is usually completed in 0.25 seconds, and increased
flow in exercise decreased the time in the capillaries
 Training is an increase in physical performance in response to a repeated
exercise, usually thought to be a 30minute session, 60% maximum O2
consumption, 2/3 times a week for 8-10 weeks
 Training on muscles  effects on muscle increase muscle strength and
resistance to fatigue is due to muscle hypertrophy, increased number of
myofibrils, increased mitochondrial enzymes, increase concentration of
ATP, phosopho-creatine and glycogen
 Training on CVS  bradycardia and cardiac remodelling, bradycardia is
due to increased ventricle size and SV, reduced blood pressure due to
 enhanced endothelial function (decreased TPR) and an increase in
capillary density, increases levels of myoglobin and 2,3 BPG
 Training on respiration  training results in reduced ventilation at the
same work rate, this may be due to lower blood lactic acid levels which
results in less feedback to stimulate breathing, but overall training had
little effect, if any, on ventilation capacity
 CV response to static exercise, where CO increases due to an increase in
HR, SV is limited by raised intra-thoracic and intra-abdominal pressure,
blood flow in muscles is a compromise between metabolite vasodilation
and contraction of muscles, dilation will increase flow, contracted muscles
will impair flow, systolic and diastolic BP both rise
 Exercise testing
o Oxygen consumption is directly proportional to the work
performed, maximum oxygen consumption reflects the functional
capacity of the entire cardiopulmonary system, VO2 max is not
routinely measured but inferred by maximum exercise capacity
o Patient exercises either on a treadmill or on a static bicycle, the use
of standard exercise protocols allows the estimation of oxygen
consumption
 E.g. modified Bruce treadmill exercise test
o Some guidelines include, contraindications if acute MI 2 days
previously, acute PE or severe arterial hypertension (above
180mmHg)
o Stop the test if moderate to severe angina, dizziness or syncope or
the subject wishes to stop
o Major risks include sudden cardiac death and MI but very rare