ANCZA Heart Physiology Combined Notes 1-6

By Adam Hollingworth
1.Electrical Heart
Table of Contents
Origin & Spread of Excitation .......................................................................................................................... 2
Anatomy .............................................................................................................................................................................. 2
Cardiac Muscle APs & Pacemaker APs ...................................................................................................................... 2
Cardiac AP .......................................................................................................................................................................... 2
Pacemaker Potential ...................................................................................................................................................... 4
SAN vs AVN ......................................................................................................................................................................... 5
Spread of Cardiac Excitation ........................................................................................................................................ 5
Cardiac Arrhythmias .......................................................................................................................................... 6
Classification ..................................................................................................................................................................... 6
Cardiac Rate ....................................................................................................................................................................... 6
Delayed After Polarisations ......................................................................................................................................... 6
Abnormal pacemakers ................................................................................................................................................... 7
Ectopic Foci of Excitation .............................................................................................................................................. 7
ReEntry ................................................................................................................................................................................ 7
Atrial Arrhythmias .......................................................................................................................................................... 7
Ventricular Arrhythmias ............................................................................................................................................... 8
Long QT ............................................................................................................................................................................... 8
Accelerated AV Conduction .......................................................................................................................................... 9
Myocardial Excitability vs Irritability .......................................................................................................... 9
ECG .......................................................................................................................................................................... 10
Unipolar Leads ............................................................................................................................................................... 11
Precordial Leads ........................................................................................................................................................... 12
His Bundle Electrogram .................................................................................................................................. 12
ECG Monitoring Systems in Anaesthetics .................................................................................................. 13
3 Electrode Systems ..................................................................................................................................................... 13
5 Electrode System ....................................................................................................................................................... 13
Modified 3 Lead System .............................................................................................................................................. 13
Surface Recordings Compared to Actual APs ........................................................................................... 13
Diseases Effecting ECGs ................................................................................................................................... 14
Myocardial infarction .................................................................................................................................................. 14
Post MI Vent Arrhythmias .......................................................................................................................................... 14
Electrolyte Effects on ECG .......................................................................................................................................... 14
1.Electrical Heart -
Origin & Spread of Excitation

Anatomy
SA node = junction SVC & R atrium
AV node = R post portion of intraatrial septrum
3 bundles of atrial fibres which connect SA & AV node:
o anterior tract of Bachman
o middle tract of Wenckebach
o post tract of Thorel
! conduction also through atrial myocytes
AV node gives of bundle of His:
o Left BB from top of interventricular septum
! Anterior fascicle
! Post fascicle
o R BB continuation of bundle of His
Branches and fasicles run subendocardially each side of septum
Contact Purkinje system
Conduction system composed of modified cardiac mm
SA node & AV node contain small round cells with gap junctions
! =pacemaker cells
Atrium separated from ventricle by fibrous ring only conduction between 2 is through His bundle
Vagus & sympathetic distribution:
o Left AV node
o Right SA node
Sympathetic fibres:
o From stellate ganglion
o Norad fibers = epicardial
Vagal fibers = endocardial
Cross connection between symp & parasymp:
o Ach acts presynaptically Norad from symp nerves
o Neuropeptide Y from symp system Ach release
Cardiac Muscle APs & Pacemaker APs

Seen atrial, ventricular & purkinje fibres:
threshold =
-65mV
Cardiac AP
Resting potential -90mV
Depolarisation spreads rapidly between cells due to gap junctions
Phases:
o 0 = rapid depolarisation towards threshold
! Na influx via fast voltage gated Na channel opening in response to AP
! Overshoot seen briefly as Na channels self inactivating
o 1 = rapid repolarisation
! Na channels close
! Ca open Ca start to flow in
! K channels open K flow out
o 2 = plateau
! Ca influx in which maintains depolarisation (via L type channel)
! Na channel closing continues which contines to repolarisation
o 3 = repolarisation
! rapid K channel
! slow K channel
! both show K out
! Na & Ca channels return to baseline state
! Ion channels & electrogenic pumps return membrane to resting potential
o 4 = return to resting membrane potential
! K channels return to baseline state
! Na/K/ATPase electrogenic pump
Refractory Period
Ventricular mm APs refractory period = ~250ms:
o ~200ms = absolute (ARP)
o ~50ms = relative (RRP)
ARP:
o extends into phase 3
o Na channels are still in an inactive state
RRP:
o -50 to -90mV
o possible to elec stim the cell but need a larger stim and resultant AP will be smaller
! contraction weaker as well (less Ca influx)
refractory plateau impt:
o tetany:
! mechanical response to multiple elect stim is one single twitch
! in skeletal mm multiple stim fused twitches ie tetany which would be bad in heart
o strength of contraction:
! influx of Ca during plateau phase s intracellular Ca
! adrenaline stim longer plateau +ve inotropy
Pacemaker Potential
seen only in SA, AV nodes

! are other latent pacemaker cells in conduction system if nodal disease
resting potential -60mV but not stable
pacemaker cells display auto-rhythmicity ie will always want to move to threshold
phase 1 & 2 of cardiac AP are absent as no depolarisation plateau
phases:
o prepotential (4) slow drive to threshold
! fall in membrane K permeability
! If = inward slow positive current displayed: (for funny current)
opening of transient Ca (T type) Ca influx
! not effecting by catecholamines
! only found in cells which lack a T tubule system ie pacemaker cells &
vasc smooth mm (not ventricular myocardium)
activity of electrogenic 3Na-2Ca exchange system
! driven by inward movement of Ca
o depolarisation (0) opening long lasting Ca channel Ca influx
! (L type) long lasting Ca channel
! produce long lasting current relative to Na
! the most predominant Ca type
! start opening during initial upstroke
! verapamil & nifedipine block them
! catecholamines activate them
o repolarisatrion (3) K channel opening K efflux
o hyperpolarisation (4) closing of K channel, opening of H channel
! passes Na & K
action potential in pacemaker cells has :
o auto-rhythmicity by K Ca K permeability
o no contribution by Na
Vagal effect on pacemaker potential:
o Cholinergic fibres
o Membrane hyperpolarised by ing K membrane permeability
o Prepotential is slower to depolarise
! Ach act on M2 receptor
o y subunit of G protein opening special K channel K efflux slows
depolarising effect H channels
o cAMP in cell slows opening of Ca channel
o all speed of firing
Sympathetic input:
o Norad acts on 1 receptor
! cAMP quicker opening of Ca channels quicker depolarisation of prepotential
other effects on pacemaker potential:
o temp speed of firing
o digoxin speed of firing esp AV node
SAN vs AVN
ionic basis same for AVN & SAN

rate of depolarisation of the pacemaker cells is slower in AVN
SAN has the highest depolarisation rate & thus drives all pacemakers cells downstream
Spread of Cardiac Excitation
Atria
AP generated by SAN spreads from cell to cell directly via gap junctions
simultaneous contraction both atria
atria separated from ventricle by fibrous tissue must go via AVN & bundle of His
Atrial depolarisation complete in 0.1s
SAN through atrial mm at 1m/sec
SAN Left atrium via Bachmanns bundle
SAN AVN via internodal pathways:
o Anterior
o Middle
o Post
SAN
= normal pacemaker of heart
lies in RA close to entry of SVC
2mm thick & 8mm long
perfused with blood via sinus node artery
2 cell types:
o small round cells (probably PMs)
o longer elongated cells
inherent d/c rate ~ 100/min
influenced by autonomic & humeral activity
depression of activity next fastest pacemaker to take over = escape rhythms
AVN
at base of RA on R side of inter-atrial septum near opening of coronary sinus
same types of cells of SAN but fever round cells
conduction speed = 0.05m/sec
has 3 zones:
o AN zone = transitional zone between atria & node
o N zone cells here have long RRP so AV conduction slows with atrial firing
o NH zone = origin of His bundle
Vagal & symp influence on the node apparent as explained previously
AV nodal delay of 0.1s
! allowing atria to finish filling ventricles before they contract

! delay can be altered by autonomic system
Ventricles
Impulses pass down R side of IV septum via Bundle of His
After ~1cm His bundle splits:
o R
o L splits into ant & post divisions
His bundle has intrinsic rate & can take over if total AVN block
! ~30-40/min
Bundle branches supply dense network of Purkinje fibres which innervate ventricles
Purkinje cells:
o largest cells in heart
o fastest conduction velocity 1-4m/s
o have long ARP help block premature atrial impulses esp at slow HRs
Depolarisation of ventricles
o starts L side of septum and moves to R
o then down to apex heart so apex activated before bases
o return along vent walls to AV groove
o depolarises from inside to outside of vent walls:
! endocardial surfaces
! interventricular septum & papillary mms prevents valve regurg & base for contraction)
! epicardial surfaces outside of RV activated 1st because of thinner walls
! last part to to depolarise = postero-basal LV
conduction speed:
o fastest purkinje system 4m/s
o slowest SA & AV node 0.05m/s
Cardiac Arrhythmias
Classification
According to site of origin:
o Supraventricular vs ventricular
o Narrow vs broad complex
According to heart rate:
o Tachy
o brady
Cardiac Rate
Normal sinus rhythm originated in SA node

Bradycardia
o Sleep
o expiration
Tachycardia:
o Inspiration! Stretch receptors in lung parasymp inhibition of cardio-inhibitory area in medulla
oblongata HR
o Emotion
o Exercise
o Fever
Delayed After Polarisations
Caused by inward current assoc with abnormally raised intracellular Ca

Cause oscillations which ectopic beats
Abnormal pacemakers
Other parts of conduction system can become pacemakers
SA node most rapid discharger of conduction system normal pacemaker
Complete heart block idioventricular rhythm indep of atria
o due to either:
! AV nodal block other AV node takes over ~45/min
! infranodal block in His bundles new pacemaker 15-35/min
! stokes Adams syndrome fainting & cerebral ischaemia
o caused by:
! septal MI
! surgical damage to His
! congen septal defects
st
1 degree block
2nd degree block:
o 2:1 mobitz
o 2:2 Wenkebach
RBBB
LBBB - also see hemiblock in a fascicle:
o Ant hemiblock L axis deviation
o Post hemiblock R axis deviation
! combinations bifasicular or trifasicular block
Ectopic Foci of Excitation

Can be encouraged by:
o symp ns activity
o abnormal electrolytes
Abnormal condtion spont d/c of His/Purkinje system or myocardium
! = ed automaticity of heart
Extrasystole = Ectopic focus discharges beat before next expected beat
Paroxysmal tachycardia = repetitive d/c of ectopic focus at rate over SA node
ReEntry
Common cause of paroxysmal tachyarrhythmias = defect in conduction permits circus movement

= transient block on one side of conduction system impulse down good side then back up diseased
side then repeat
in AV node re-entry:
o retrograde flow back up diseased side atrial depolarisation
o next beat = echo beat
o depolarisation then circus back down good side and continue
non-AV node re-entry:
o abnormal extra bundle of connecting system connecting atria & vent
! = bundle of Kent
o wave down AV node, retrograde through bundle of kent
circus movements seen in atrium & vent
Atrial Arrhythmias
atrial extrasystole :
o ECG changes:
! P wave abnormal
! QRST normal
o Extrasystole may depolarisation SA node must repolarise before next normal beat
! see pause which allows natural reset of rhythm
Atrial tachycardia
o Rate up to 220/min
1.Electrical Heart - 7
o when:
! Regular atrial focus d/c
! Re-entry circus tachy
Atrial flutter:
o Atrial rate 200-350
o Anticlockwise circus in R atrium
o Assoc 2:1 or greater Av block
! as AV cannot conduct >230 beats/min
AF:
o Atrial rate 300-500 irreg disorganised fashion
o Vent rate 80-160
o Cause unknown but include:
! Multiple re-entrant circus excitation
! Ectopic foci often seen in pulmon veins ~4cm from heart
Consequences Atrial Arrhythmias
If high vent rate diastolic filling heart failure
Vagal stimulation effects:
o Ach conduction in AV node & atrial myocardium
o AV block
digoxin also blocks AV node
Ventricular Arrhythmias
ectopic vent focus extrasystole:

o ECG:
! abnormal QRS
! P may be buried in QRS
o unable to depolarise bundle of His no retrograde flow
o no resetting of rhythm as in atrial ectopics
! longer compensatory pause after ectopic
! SA node continues to fire regularly irrespective of vent activity
o common & usually benign
o if early in diastole: may not be strong enough to create pulse at wrist
Vent tachycardia (VT) =
o Due to circus movement in ventricles
o Torsade de pointes:
! Form of VT with varying QRS morphology
o Serious as CO
o VF occasional complication of VT
SVT with conduction block can be diff to differentiate with VT
! need HBE VT will not have a H spike
VF:
o Muscle fibres contract in irreg and ineffective way
o Due to multiple ectopic focus or circus movemt
o Can be induced by defib during vulnerable period
! Vulnerable period = midportion of T wave
=when ventricular muscle at diff stages of de & repolarisation
! great time to start circus movmt
o most common cause of death in ACS is VF
Long QT
long QT ventricular repolarisation is irreg incidence of arrhythmia

caused by:
o ischaemia
o drugs
o electrolyte abnormalities
o congenital genes encoding for Na & K channels mutated
Accelerated AV Conduction
WPW
additional aberrant connection between atria & vent:
o types:
! muscular or
! nodal tissue ie bundle of Kent
o conducts more rapidly than AV node one vent excited before other
ECG change:
o short PR interval
o upstroke slur
o normal PJ interval (start P to end QRS)
arrhythmias start:
o following atrial extrasystole
o beat goes 2 ways:
! through AV node, retrograde through aberrant pathway back to atria
! through aberrant pathway, retrograde through AV node (less common)
congenital element:
o mutation in AMP activated protein kinase
o ?involved in suppressing development of abnormal pathways in utero
Lown-Ganong-Levine Syndrome
short PR & normal QRS
beat bypasses AV node by abberant conduction pathway but then joins intraventricular conduction
system before depolarising vents
Myocardial Excitability vs Irritability

excitable =
o ease with which myocardial cell can respond to stimulus by depolarization
o index of excitability:
! AP is initiated at different stages of the RRP
! = The slope of phase 0 at this point
! steeper slope = more excitable cell & faster velocity of conduction
o hypokalaemia = hyperpolarised RMP (more ve) but actually see ed excitability
o hyperkalaemia = RMP moves towards zero. may see initially ed excitability. BUT in long
term see excitability due to inactivation of Na channels. Significant K will eventually cause
heart to stop in diastole.
irritable =
o used in context of a resting myocardial cell during phase 4
o = size of stimulus needed to depolarize cell
o index difference between current potential & threshold potential
o ed irritability = difference smaller depolarisation easier
! but there is gradient & conduction velocity of phase 0
o Ca irritability ie = cause of tetany
ECG
standard ECG =
o 25mm/sec 0.04sec/small sq, and 0.2 sec/big square
o 1mV = 1cm
Einthovens triangle =
o heart at centre with 3 limb leads around
o triangle between shoulders & pubic symphysis
o electrodes record cardiac electrical activity in vertical plane
o 3 standard limb leads records electrical activity from 2 corners of triangle:
! lead I = RA LA
! lead II = RA LF (left foot)
! lead III = LA LF
(4th electrode acts as an earth)
Depolarisation towards = upward deflection
Depolarisation away = downward
Repolarisation toward = downward
Repolarisation away = upward
P = atrial depolarisation
QRS = vent depolarisation & atrial repolarisation
T = vent repolarisation
QT = total duration of vent depolarisation & repolarisation
U = not always seen repolarisation of papillary mms
J point = junction between QRS & ST segment
Lead 2 Example
Lead 2 lies in axis of heart
P wave: atrial depolarisation SAN AVN which is down & Left (ie dep toward = upward)
Small initial Q wave: depolarization starting in IV septum spreading down & right (ie dep away =
downward)
Large R wave = depolarisation spreads endo epicardial & larger bulk of LV means net effect is
down & left (ie dep toward = upward)
Small S wave = activation of remaining ventricle, wave spreading upwards ie (dep away =
downwards)
T wave = ventricular repolarisation moving from epicardial to endocardial (ie repol away = upward)
ECG Intervals
PR = 0.12-0.2 secs
! AV delay (0.1sec) accounts from most of delay
QRS = <0.12
QT = 0.3 0.43
! varies inversely with HR
ECG Pattern
aVL & aVF look at ventricles mostly positive
V1-V2:
o No Q wave
o Small initial R wave 2nd to L to R septal depolarisation
o Large S wave depolarisation down septum & into ventricle away from electrode
V4-V6:
o Small q = initial depolarisation across septum L to R
o Large R septal and vent depolarisation
o Mod S late depolarisation of vent moving back to atria
Cardiac Axis
Mean QRS vector = -30 to +110
L axis deviation if axis to left (up or <) of -30
R axis deviation if axis to R (down or >) of +110
Unipolar Leads
3 electrodes of standard limbs leads are connected to each other
use resistances of 5000 Ohms
can create a central terminal with zero potential
! = common electrode
exploring electrode can be combined with common electrode to create central terminal
here potential difference between them = actual potential
central = reference = zero
12 lead ECG 3 unipolar leads are recorded ie aVR, aVL, aVF

a = augmented
Goldberger modification = resistances removed & exploring electrode disconnected from central
terminal larger deflections
Precordial Leads
Place electrodes closer to heart around thorax

Neutral electrode formed by standard leads
Exploring electrode placed at 6 different sites on chest wall (V1-6)
His Bundle Electrogram

Catheter placed next to tricuspid valve:
A = AV node activated
H = transmission through His bundle
V = ventricular depolarisation
With HBE & ECG can measure 3 intervals:
o PA interval =
! start of P to A wave
! = conduction time from SA node to AV node
o AH interval:
! Start of A wave to start of H spike
! =AV nodal conduction time
o HV interval
! Start H to start of QRS
! = conduction in bundle of His & bundle branches
AH time >double others ie AV node very slow to conduct
ECG Monitoring Systems in Anaesthetics

3 Electrode Systems
ECG observed alone 1 bipolar lead between 2 electrodes

3rd electrode = ground
selector switch allows you to change between electrodes
simple system to monitor rate & rhythm
limited info on myocardial ischaemia
5 Electrode System
allows for recording of all standard 6 limb leads as well as one precordial lead
! usually V5 good for ant ischaemia detection
Modified 3 Lead System

3 lead system modified to give better results:
o maximise P wave height for diagnosing arrhythmias
o incr sensitivity to detect ant ischaemia
several modifications exist
one example = CS5 lead:
! = bipolar lead best & easiest alt to true V5 lead for monitoring ischaemia
o RA electrode placed under R clavicle
o LA electrode placed in V5 spot
o LL in usual spot for grounding
o Leads:
! Lead 1 = detection ant ischaemia
! Lead 2 = inferior ischaemia/arrhythmias
Surface Recordings Compared to Actual APs
Diseases Effecting ECGs

Myocardial infarction
Early Pattern
3 major changes - all cause ST elevation
1. Rapid Repolarisation current out of infarct
rapid repolarisation of infarcted muscle fibres
due to faster opening K channels
develops seconds after infarct
lasts few minutes
2. Decreased Resting Membrane Potential current in
more K channels open ed K efflux resting membrane potential lower
causes TQ segment depression
! on ECG looks like ST elevation
3. Delayed Depolarisation current out
30min after infarct
Later Pattern
hours few days

dead mm & scar tissue electrically silent
infarcted area negative compared to norm myocardium during systole path Q waves
anterior L vent infarction failure of progression of R wave
septal infarction BBB or other heart block
Late Established Pattern
days to weeks
ECG:
o Q waves persist
o ST segments isoelectric
o T inversion where previous ST elevation; Tall Ts where prev ST depression
May persist for rest of life
Very Late Pattern
Months to years
Path Q waves persist
T waves gradually return to norm
Post MI Vent Arrhythmias

timing:
o 30mins post re-entry arrhythmias common
o 12hrs post due to ed automaticity
o 3days post due to reentry
damage to epicardial regions interrupt sympathetic nerve fibres
o denervation super-sensitivity to catecholamines in area beyond infarct
damage to endocardial regions interrupt vagal fibres unopposed sympathetic action
Electrolyte Effects on ECG
Na
Na: low voltage ECG
Hyperkalaemia
changes in sequence:
o tall peaked T waves
o paralysis of atria loss of P waves
o prolonged QRS
resting membrane potential of myocardium s excitability of myocardium heart stops in
diastole
Hypokalaemia
in sequence:
o ST segment depression
o U wave
o PR prolongation
o T inversion
not as fatal as hyperkalaemia
Hypercalcaemia
ed myocardial contractility & ed ability to relax
! in vivo difficult to get plasma Ca levels high enough to effect heart
Hypocalcaemia
prolongation of ST segment prolongation of QT
! mimicked by drugs incl TCAs, phenothiazines
2.Heart as a Pump
Table of Contents
Cardiac Cycle ......................................................................................................................................................... 2
CVS Pressures .................................................................................................................................................................... 3
Heart Failure ..................................................................................................................................................................... 3
Pericardium ....................................................................................................................................................................... 3
Timing .................................................................................................................................................................................. 4
Length of Systole & Diastole ......................................................................................................................................... 4
Arterial Pulse ........................................................................................................................................................ 4
JVP ............................................................................................................................................................................. 4
Cardiac Graph ....................................................................................................................................................... 5
Heart Sounds ..................................................................................................................................................................... 5
Murmurs ............................................................................................................................................................................. 6
Cardiac Output ...................................................................................................................................................... 6
Measurement .................................................................................................................................................................... 6
Factors effecting CO ........................................................................................................................................................ 6
Definitions .......................................................................................................................................................................... 6
Preload .................................................................................................................................................................... 7
Factors Effecting EDV ..................................................................................................................................................... 8
Relation of Tension to Length in Myocardium (Starlings Law) ........................................................................ 9
Afterload ................................................................................................................................................................. 9
Myocardial Contractility ................................................................................................................................. 10
Positive Inotropic Factors .......................................................................................................................................... 10
Heart rate ............................................................................................................................................................. 12
O2 Consumption ............................................................................................................................................................ 13
Summary Effects on CO .................................................................................................................................... 13
Functional Factors Effecting CO Overall .................................................................................................... 13
Ventricular Function Curves .......................................................................................................................... 15
Ventricular Pressure Volume Loops ...................................................................................................................... 15
Vascular Function Curves ............................................................................................................................... 18
Coupling Between Heart & Vasculature ..................................................................................................... 20
Athletes, Heart Transplant & Sympathetic Control of CO .................................................................... 23
Heart as a pump -
Cardiac Cycle
With av HR of 72/min:
o Total cycle = 0.8 seconds
o Systole = 0.3 s
o Diastole = 0.5s
! vent filling ~ 2/3 cycle
Mid Diastole
Atrial & vent pressure both low

Rate filling ventricles as V pressure rises above A pressure due to wall stretch
vents now 80% full
cusps of mitral/tricuspid valves drift towards closed
80% vent filling occurs passively
Atrial Systole (late Diastole)

SA node fires P wave on ECG atrial contraction (atrial a wave)
contraction of atria narrows IVC & SVC orifices to backflow
! is some regurg
see small rise in vent pressure
atrial kick contributes ~20% vent EDV
! (vent EDV in supine ~160ml; stand ~130ml)
impt in fast AF with loss of kick
Vent Systole
@ start AV valves close isovolumetric contraction:

o 1st heart sound
o sharp rise in intravent pressure
o lasts 0.05s
o mitral/tricuspid valves bulge into atrium
! = C wave of atrial pressure wave (pressure LA:10mmHg. RA:5mmHg
once ventr pressure higher than aorta & pulmon ejection
rapid vent ejection phase after valve open followed by prolonged reduced phase
pressure changes:
o aorta: 80120
o pulmonary a: 525
late systole : pressure aorta > L vent but momentum keeps blood flowing
elasticity of aortic walls & periph resistance to flow maintain aortic pressure
SV ~ 70-90ml
End diastolic vent volume ~ 120ml
Ejection fraction ~65% in norm heart
End systolic vent volume ~50ml
Atria:
o Rapid ejection phase: mitral/tricuspid valves pulled down by vent systole atrial pressure
aiding filling
! = x descent
o Rest vent systole: rise atrial pressure as blood fills atria = v wave
(! in tricuspid regurg c & v merged into one large v wave)
Early diastole
Protodiastole =
o Before aortic/pulmon valve closed
o Rapid drop vent pressure
o Lasts 0.04s
o Ends with valve closure
Isovolumetric vent relaxation:
Heart as a pump -
o Begins with closure of aorta & pulmon valves (2 heart sound may be split if aortic closes 1st)
o Incursura in aortic pressure waveform produced by closure of valve causing brief backflow of
blood
o Atrial pressures: LA ~5mmHg; RA ~2mmHg
o Ends when vent pressure falls below atrial pressure mitral/tricuspid valve opening
Atrial pressure s after systole until mitral/tricuspid valves opens
Rapid filling of ventricle occurs after mitral/tricuspid opening most impt part of vent filling as time
to fill is shortened with tachycardia
Y descent of atrial pressure as it empties
nd
CVS Pressures
Heart Failure
Systolic failure =
o weakened systolic contraction
o ejection fraction
o responses:
! activation of genes myocardial hypertrophy
! symp n.s.
! renin & aldosterone secretion Na & water retention
! initially compensatory but then failure worsens with ventricular dilation
diastolic failure:
o elasticity of myocardium filling of vent in diastole SV same responses in systolic
failure
high output failure:
o relative low CO (not absolute)
o seen in:
! large AV fistula
! thyrotoxicosis
! thiamine deficiency
Rx:
o ACEI - VC & aldosterone volume bp afterload
o Nitrates venous VD preload
o Diuretics fluid overload preload & afterload
o B Blockers - chance of arrhythmia
o Digoxin - Ca [in] force of contraction
Pericardium
Myocardium epicardium pericardium

Heart as a pump -
Between epicardium & pericardium = 5-30ml fluid
Timing
R atrial systole then L atrial systole

Left ventricular contraction then R vent
R vent ejection just before L vent
! as pressure in pulmon circuit < aortic pressures
End of systole (S2 heart sound)
o During inspiration pulmon valve closure delayed
o During expiration aortic & pulmon valves together
Length of Systole & Diastole
Duration of systole is more fixed than diastole

! although speed of systole does decr with HR
Marked decr in diastole with high HRs results in:
o vent filling
! up to 180/min filling adequate if enough venous return
o perfusion of coronary circulation
cardiac mm cannot tetanise like skeletal mm
max theoretical rate of vents =400
only see rate >230 in vents in VT
! max AV node d/c rate
Arterial Pulse
pulse felt is a pressure wave NOT blood moving forward
pressure wave moves faster than blood flow:
o aorta 4m/s
o large arteries 8m/s
o small arteries 16m/s
! older rigid arteries wave moves faster
pulse pressure strength of felt pulse eg
! no relation to mean pressure
o shock narrow pulse pressure 2nd to diastolic pressure thready pulse
o aortic insufficiency high pulse pressure 2nd to regurg & diastolic collapsing pulse
dicrotic notch =
o notch on falling phase of pulse
o unable to feel; only measure
o vibrations from aortic/pulmon valve shutting
JVP
atrial pressure:
o in atrial systole
o in isovolumetric contraction bulge of AV valve into atria
o rapid in early systole AV valves pulled into ventricle
o slow through systole atrial filling
o as AV valves open in diastole
JVP waves:
o A atrial systole
o C isovolumetric contraction - bulging of AV-valves into atrial chambers
o V rise in atrial pressure until tricuspid valve opens (due to atrial filling during ventricular
systole (lasts until end of isovolumetric relaxation))
Heart as a pump -
o x-descent: (follows c wave) initial pressure drop in atria during initial rapid ventricular ejection
= due to atrial relaxation as well as ballistic effect of contracting ventricles on atria.
o y-descent: (follows v wave) drop in atrial pressure as AV valves open at end of isovolumetric
relaxation and onset of early diastole.
Respiration effects volume of JVP waves:
o Inspiration & ed -ve intra-thoracic pressure venous pressure
o Expiration venous pressure
Cardiac Graph
= Wiggers diagram:
Phases:
1. atrial systole
2. isovolumetric contraction
3. vent ejection
4. isovolumetric relaxation
5. vent filling
Heart Sounds
S1 = closure of AV valves = start of systole
S2 =
o closure of aortic & pulmon valves = end of systole
Heart as a pump -
o inspiration physiological splitting of S2 by late closure of pulmon valve due to incr preload
S3 (always follows S2) =
o rapid vent filling 1/3 through diastole
o can be normal
S4 =
o Filling of stiff ventricle following atrial contraction
o Just before S1
o Always pathological
Murmurs
Blood flow speeds up through narrowing eg:

o stenosis
o regurgitation
turbulent flow murmur
aortic or pulmon valve:
o stenosis systolic
o regurg diastolic
AV Valve:
o Stenosis diastolic
o Regurg systolic
Cardiac Output
Measurement
Fick principle = amount of substance taken up by organ/time = arterial level of the substance minus the
venous level (A-V difference) x blood flow
Norm CO = ~70ml/kg/min or 5 litre/min
Cardiac index =
o CO/body surface area
o output/min/m2
o norm ~ 3.2
! CI adjusts for differing body sizes
Factors effecting CO
CO = HR x SV
As circ is a close system CO usually = VR
SV determined by:
o Loading factors
! preload (PL)
! afterload (AL)
o Myocardial contractility (Cx)
4 determinants of CO:
o HR
o Cx
o AL
o PL
! All these factors also determine Myocardial O2 demand
Definitions
Preload = amount of stretch of ventricular mm fibres at end of ventricular filling (aka inial fibre
length)
Afterload = impedance to the ejection of blood into the arterial circulation
o Impedance rather than resistance as it is a changing resistance
o Afterload because ventricle only performs work after the aortic valve opens
Heart as a pump -
Contractility = factor responsible for changes in myocardial performance which are not due to HR,
preload or afterload
! not to confuse with Starlings law)
All myocytes display 5 chars:
o Bathmotropy = excitability
o Dromotropy = conductivity
o Chronotropy = rhythmicity
o Inotropy = contractility
o Lusitropy = relaxation
Preload
Starlings Law of heart = diastolic length of vent mm fibres determine the force of their contraction
! ie intrinsic quality of cardiac myocytes NOT contractility
Amount of vent mm fibre stretch at end of diastole forms basis of Starling Law
Summary preload factors:
o filling pressure CVP:
! blood volume
! gravity
! Tx pump
! mm pump
! CO
! periph tone
o ventricular compliance
Right Side of Heart
cannot measure stretch but EDV is next best indicator of preload
EDV can be measured with ECHO
Another indicator of preload = end-diastolic pressure (EDP) aka filling pressure
EDV is proportional to EDP but EDV achieved will depend on ventricular compliance
compliance = V / P
EDV = ventricular compliance x filling P
Left Side of Heart
LVEDP cannot be measured directly
next best way to determine LV preload is surrogate pressure measurement = PCWP
PCWP theory:
o End diastole: continuous communicating coloum of blood from LV LA pulm veins
pulmon caps
o Inflate pulmon art catheter balloon, float pressure sensor distally until wedged in pulmon
capillary
o Pressure measured is PCWP
o Ideally catheter should be in West zone 3 (Pa>Pv>PA)
Next surrogate of LV preload = CVP:
o CVP RAP RVP PAP PCWP LAP LVP LV volume LV preload
Downsides of R side pressure surrogates of LV preload are many!!:
o Valvular disease
o Pulmon disease
o Changes in LV/RV compliance
Heart as a pump -
Factors Effecting EDV

EDV depends on:
o Compliance of ventricle
o Transmural pressure distending it:
! = internal pressure external pressure
! external p = intrathoracic pressure
compliance:
o compliance EDV for a given distending pressure
external pressure:
o ITP (intrathoracic pressure)
! end expiration = -5cmH20
! end inspiration = -10cmH20
! inspiration creates a suction effect around heart & central veins vent filling
internal pressure:
o EDP in RV ~ CVP
o Therefore CVP plays key role in determining preload.
Factors influencing CVP
Blood volume:
o 2/3 of total blood volume is in venous system
o any in volume sig in CVP
gravity:
o influence distribution of venous blood between periph & thoracic veins
o eg ~500ml blood pools in LLs in erect position
Periph venous tone:
o Esp skin, kidney, splachnic veins
o Innervated by symp ns venoconstriction CVP
MM pump: esp impt in exercise VR CVP
Throacic pump:
o With ing insp negative ITP & abdo pressure +ve venous gradient from abdo to thorax
! venous valves prevent back flow during expiration
Cardiac output:
o Heart transfers blood from venous to arterial system MAP & CVP
o Everything else being the same MAP & CVP acts as a brake
Functional Examples
decreasing EDV:
o intrapericardial pressure
! eg pericardial effusion,
! pressure from tumour
o ventricular compliance:
! MI
! Inflam disease
increasing EDV:
o atrial contraction
o hypervolaemia venous return
o pressure gradient to heart along venous flow:
! inspiration
! muscular activity
! moving to lying
Heart as a pump -
Relation of Tension to Length in Myocardium (Starlings Law)
Nb force of contraction or initial fibre length difficult to measure

o Y axis usually = CO, SV, stroke index, stroke work
o X axis usually = LVEDV, LVEDP, PCWP
Curve also known as ventricular function curve
! in vitro measurement
Starlings law of heart = energy of contraction is to initial length of cardiac mm fibre up to a point
This is defined by myocardial sarcomere length (~2.2um) & ratchet mechanism:
o Immediate rise in contractile force due to overlapping actin filaments & myosin bridges
o Delayed response (over mins) - in systolic calcium flux due to stretch sensitive Ca channels
Starling mechanisms function:
o Balance outputs of R & L ventricle:
! 1% difference in RV > LV output over 30mins pulmon blood from ~600mls to
~2100mls severe pulmon oedema
! RV output > LV LVEDV starling mechanism LV output
o Valsalva Manoeuvre causes fall in SV
o In upright exercise: if CVP rises contributes to SV
o Mediates postural hypotension
o Mediates arterial hypotension following haemorrhage
Guyton Cardiac Function Curve
= in vivo curve
Displays pivotal role of CVP in regards to CO
Shows how CVP raised the CO by means of Starling mechanism provided HR & MAP are unchanged
Differs from Starling vent function curve in that is affected by changes afterload & contractility ie
invivo
! a ventricular function curve shows only Frank Starling relationship ie isolated mm strip (in
vitro)
Homometric regulation = changes of contractility not due to change in fibre length
! ie autonomic system, drugs, ischaemia
heterometric regulation = changes in CO due to mm fibre length changes
Afterload
afterload = impedance to vent ejection
function of:
o SVR
o Laplace law: ventricular wall tension
! T = P.R/wall thickness
! intrathoracic pressure seen with IPPV afterload via R & wall thickness
o aortic root compliance
Heart as a pump -
o aortic valve dysfunction
for LV = MAP during systole; for RV = mean pulmonary arterial pressure (during systole)
MAP = CO x SVR (chief site of resistance = arterioles)
NB:
isotonic cardiac contraction = against a fixed afterload (in vitro only)
auxotonic = contraction against a changing afterload (happens in vivo)
Effect of Afterload
afterload is reflected by myocardial wall tension (T)
ventricular hypertrophy wall tension by ing wall thickness
! explained by La Places Law:
for thin walked spheres or tubes:
P = 2T/r
can rearrange:
T=Pxr/2
For thick walled sphere or tube:

Tension = wall stress (S) x wall thickness (w)
wall stress =
Pxr
2w
thus wall stress ed by:

o pressure in chamber (afterload)
o radius (dilated heart)
thus wall stress ed by:
o wall thickness (LVH)
it is the ed wall stress which s myocardial o2 demand
Myocardial Contractility
Starling mechanism = intrinsic regulation of contractile strength
myocardial contractility = extrinsic or change in contractile energy not due to fibre length changes
inotropic state = contractility
Positive Inotropic Factors
Positive inotropic effect on heart shifts length-tension curve UP & LEFT eg:
o Symp n.s. =
! norad release at symp nerve terminals
! circulating catecholamines ie norad, adrenaline, dopamine
act on 1 receptors cAMP
o Drugs:
! Xanthines eg caffeine & theophylline
Phosphodiesterase inhibitor breakdown of cAMP
! Digoxin inhibitory effect on NaK ATPase indirect inhibition of NCX pump
! Angiotensin 2
! extracellular Ca
! thyroxine
o Force frequency relation:
Heart as a pump - 10
! Vent extrasystole condition next beat to be stronger
! Due to Ca [in]
o HR
! small incr in contractility
! not very much in vivo
! if HR ed the 1st beat is weaker than following beats with progressive in strength
! = Bowditch rate effect
! due to size of calcium influx
Noradrenaline effects
=most impt ionotrope
NA released from symp nerve terminals in vent wall:
o binds to B1 receptors on myocytes ( GS linked)
o activates a prot cAMP prot kinase A calcium channel phosphorylation sequence
o inward calcium current during the plateau of the AP intracellular calcium stores more
forceful systolic contraction
In addition:
o sarcoplasmic reticulum calcium uptake pumps are accelerated shorter systole
o This is beneficial as it preserves diastolic filling time (impt in tachycardia)
! This property (ie relative shortening of systole) is called lusitropy.
Thus the effect of NA is a more forceful and shorter systole, which results in following:
o ed bp: Ventricular pressure s more rapidly in the isovolumetric phase
o ed Ejection fraction: - velocity of contraction and shortening are enhanced by NA.
! EF is sometimes used as an indirect index of contractility
o Stroke volume: ! Transient as EF rises, BUT
! then limited by the concomitant in EDV as well as MAP.
o ed Systolic duration: (lusitropy) shorter ejection time does not significantly curtail SV,
because the velocity of shortening is increased. (ie more forceful contraction).
**** **** ******
Negative ionotropic DOWN and to RIGHT
o Para symp = vagal tone via Ach
o CO2, O2
o ischaemia via acidosis & hypoxia
o drugs:
! BBs & CCBs
! Barbituates
! Many anaesthetic drugs
o heart failure intrinsic depression:
! ? cause but thought:
regulation of B receptors
Ca liberation from Sarcoplasmic reticulum
Heart rate
CO = SV x HR
Any change in HR usually occurs as part of integrated response to a MAP
HR under autonomic control:
o Symp HR
o Parasymp HR
Heart = demand pump any change in HR will only effect CO if assoc with change in demand from
tissues
Tissues set their demand by means of total venous return tendancy for VR Starling
mechanism adjustment of CO
! VR = CO
Isolated Changes in HR
Eg pacing, atropine
Will see surprisingly little change in CO (within limits)
! cos see an inverse change in SV for any change in HR
Isolated HR:
o artificial pacing rate diastole but not systole ed vent filling time
o transfer of blood from venous side to arterial side EDP & MAP both of which SV
! at a threshold actually start seeing CO due to ed vent filling time
isolated HR:
o initially CO will remain constant:
! HR offset by vent filling time SV
o at threshold will see a CO as ventricles max filled ing HR ing CO
O2 Consumption
o2 consumption determined by:
o intramyocardial wall stress (surrogate for afterload)
o contractile state of heart
o HR
Ventricular work = SV x mean arterial pressure
! thus LV work x7 more than RV
Pressure work requires o2 consumption compared to volume work ie afterload > preload
! incompletely understood
! why angina is more common AS : AR
basal o2 consumption 2ml/100g/min
! much bigger than skeletal mm
beating heart 9ml/100g/min
in o2 consumption require in blood flow
Summary Effects on CO
4 determinants of CO:
o HR
o Cx
o AL
o PL
! All these factors also determine Myocardial O2 demand
But any change in single factor remarkable ineffective
Need coordinated cooperative change in all factor to change CO substantially
Functional Factors Effecting CO Overall

No change:
o Sleep
o Mod changes in environmental temperature
Increase:
o Anxiety 50-100%
o Eating 30%
o Exercise up to 700%
o temp
o pregnancy
o Adrenaline
Decrease:
o Lie to sit/stand 20-30%
o Arrhythmias
o Heart disease
Ventricular Function Curves

Ventricular Pressure Volume Loops
Normal P-V loop for LV:
All the information obtained from Vent P-V loop (favourite exam topic):
o EF
o LVEDV Note: this is number on x axis NOT point B
o Indices for afterload = Ea line
o Indices for ventricular compliance (EDVP Line)
o Contractility = Ees line
o Stroke work (PxV = Joules) = area within loop
o B-A = diastolic filling
o C-B=isolvolumetric contraction
o D-C = volume ejected
o D-A= isovolumetric relaxation
EDPV Line
P-V relationship during diastole (AB) gives an idea of ventricular compliance
! most important part of line is End Diastolic P-V line (EDPV)
P is plotted against V talk about elastance (ie inverse of compliance)
EDVP line as shown

ESPV Line
Similar line to EDVP but drawn on top of ventricular function curve at End systole
Aka endsystolic elastance of EEs line ie measure of contractility
Effect of Isolated Preload on LV PV Loop

Loop 1 = normal; loop 2 shows ed preload
Loop 2 has ed stroke volume as wider
Contractility & afterload are constant
(Ea line)
Effect of Isolated Afterload

Index for afterload =
o slope of line connecting LVEDV & End systolic point
o aka effective arterial elastance (Ea line)
In loop above this line parallel; in this loop clear in afterload in loop 2
Loop 2 has ed SV 2nd to ed afterload which manifests as earlier aortic valve closure
(Ea line)
Effect of ed Contractility
LVEDV is same for both loops ie preload same
Ea line is the same ie afterload same
ESPV Line = index of contractility
Loop 2 demonstrates SV by mechanism of isolated contractility ESPV ed gradient
ESPV Line
(Ea line)
NB: Above lines demonstrate differences in vitro. In body more integrated changes seen
Effect of Systolic & Diastolic Dysfunction
L curve = systolic dysfunction:
o ed stroke volume
o curve also implies afterload ed by steeper Ea line (not drawn)
R curve = diastolic dysfunction:
o EDPV shifted up and left ie preload ed due to elastance SV
Mechanical Energy & Work
= a pressure volume area
Area within the loop = stroke work (mechanical energy) done by heart during single contraction
! = external work of ventricle
Isovolumetric contraction (upstroke):

o no ejection & no external work
o energy expended to generate potential energy converted to heat during diastole
Potential energy:
o Purple triangle (EDPV ESPV isovolumetric relaxation line)
o = amount potential energy available during a contraction
! correlates well with heat generated during contraction
total mechanical work + heat generated = PVA of stroke work + potential energy
! pressure volume area
PVA correlates well with O2 consumption (VO2) of myocardium during single contraction
Gross energy efficiency of heart ~15%:
o Much of contractile energy goes into raising pressure rather than ejection
o bp can improve SV in heart failure
metabolic energy source variable:
o 2/3 FFAs
o rest = glucose & lactate
! heart is an omnivore
Vascular Function Curves

Starling Curve (&Guyton Curve) = cardiac function curves which relate:
o Change CVP x axis (indep variable)
o Change in CO y axis (dependant variable)
! ie how changes in CVP effect CO
! = a compliance curve
Vascular function curve relates: (switch-a-roo)
o Change in CO x axis (indep variable)
o Change in CVP y axis (dependant variable)
! ie how changes in CO effect CVP
! = a elastance curve
Impt points:
o CO = 0 ie cardiac arrest:
! Pressure becomes an equilibrium throughout whole CVS ie not just venous
! This = Mean circulatory pressure (MCP) (or Pmc as in diagram)
! MCP ~ 7mmHg ie vascular system overfilled
o Point A:
! @normal CO ~5l/min
! CVP = ~2mmHg
! = norm operating pressure of system
o Break point of line below point A:
! ing CO ing CVP up to a point
! here intravascular pressure falls < extravascular pressure collapse of distensible large
vessels
! CO now limited by VR & cannot anymore
o If a VFC is combined with a CFC then CFC axis orientation take precedence for convenience
Effect of Change in Blood Volume & Venous Tone
Transfusion or venoconstriction upward shift of curve ie ed MCP
! converse is true ie haemorrhage & venodilation downward curve shift
NB neither will affect position or shape of cardiac function curve!!
Effect of change in SVR (ie afterload)

MCP does not change only ~3% of total blood is in the arterioles
Vasodilation larger CO (or VR) anticlockwise rotation of VFC
Vasoconstriction CO (or VR) clockwise rotation of VFC
NB change in SVR (VasoC or VasoD) will also effect cardiac function curve
Coupling Between Heart & Vasculature

NB CO = VR ie both describe total flow around closed circuit
Coupling can be demonstrated by plotting CFC & VFC on same graph (with CFC axis orientation)
(! Guyton)
Intersection of 2 curves = equilibrium point at which CVS tends to operate
Curve shows how disturbances in equilibrium are dealt with:

o CVP:
! CFC moved to point A
! ed CVP would CO ie point A point B during next systole
! As a result of CO NET transfer of blood from venous to arterial side of circ CVP
(due to VFC)
! With each beat this transfer would be small ie point B point C (not B C1)
! Due to CVP next CO of next beat will also be ed (due to CFC) ie point C D
! Point D is still above equilibrium heart will pump blood from venous to art circ every
beat at a rate faster than blood will flow across peripheral capillaries back to venous
circulation CVP continue to until equilibrium reached
! above example needs total volume to stay same ie inject blood into venous side during diastole,
while simultaneous removing same volume from arterial circ
Effect of ed Contractility on Cardiac-Vascular Coupling
Isolated ed contractility due to symp stim
! in vitro demonstration cos symp stim would also have effect on vasculature in vivo!
equilibrium values will change:
o CO shift upto point B (due to ed contractility ie no change in CVP initially)
o NET transfer of blood to art side ing CVP (B to C)
o CO will continue to fall until reach new equilibrium (C to D)
! at intersection of same VFC but with new CFC
Summary effect = SNS stim greater CO at same CVP

! VFC is the same!!
Effect of Changes in SVR
SVR (vasoC) effects both CFC & VFC downwards
@equilibrium for an SVR CO (point A to B)
Effect of Transfusion on Coupling

VFC shifted parallel up to right
CFC not changed
CO & CVP are both ed (point A to B)
! the CVP is reflected on the CFC by Starlings Mechanism ie moves along curve but does not
change its shape
Coordinated Effect of Max Symp Activity (in Vivo)

CFC is shifted up & left - contractility overrides the afterload effects
VFC shifted:
o Up venoconstriction predominant
o Slight rotation down vasoconstriction = less predominant
Effect of Heart Failure
Acute pump failure:
o Mod to severe failure: CFC shifted right & down
o Blood volume remains constant immediately
o equilibrium (point A) will slide down normo-volaemia line
! equilibrium point of will correspond to ed contractility (point B or C)
Chronic congestive Heart failure:
o blood volume VFC shift upwards
! 2nd to aldosterone fluid retention & GFR
o CFC remains shifted down and right from pump failure (contractility)
o mod heart failure can maintain norm CO (point D) but with higher CVP
o BUT with severe failure COing & CVP remains high
Disparate changed in vent contractility:
o Eg ant MI effecting LV only LV contractility but norm RV contractility
o Initially LAP norm but LV output
o RV continue with norm output
! ing RAP ing RV output
! ing LAP LV output
! both via CFC effects
o continue until new equilibrium reached & 2 vent will have same outputs BUT ed L sided
pressures pulmon venous P which can lead to pulmon oedema
Athletes, Heart Transplant & Sympathetic

Control of CO
During exercise = symp activity HR & SV
o In untrained individuals: bigger HR; less SV
o In trained athlete: less HR; bigger SV
o In heart transplant: no direct symp innervation thus
! Circulating catecholamines small effect
! EDV vent contraction SV
! mm pump venous return
! Respiration venous pressure gradient
! VD of arterioles in mm afterload CO
3.Dynamics of Blood Flow

Table of Contents
Intro ......................................................................................................................................................................... 2
Vessels ..................................................................................................................................................................... 2
Vascular Smooth Muscle ................................................................................................................................................ 2
Arteries & Arterioles ...................................................................................................................................................... 2
Capillaries .......................................................................................................................................................................... 2
Lymphatics ......................................................................................................................................................................... 3
A/V Anastomoses ............................................................................................................................................................. 3
Venules & Veins ................................................................................................................................................................ 3
Angiogenesis ...................................................................................................................................................................... 3
BioPhysics .............................................................................................................................................................. 4
Equations ............................................................................................................................................................................ 4
Flow, Pressure, Resistance ........................................................................................................................................... 4
Laminar Flow .................................................................................................................................................................... 4
Shear Stress ....................................................................................................................................................................... 5
Average Velocity ............................................................................................................................................................... 5
Flow & Radius ................................................................................................................................................................... 5
Viscosity & Resistance .................................................................................................................................................... 5
Critical Closing Pressure ............................................................................................................................................... 5
Law of Laplace ................................................................................................................................................................... 6
Resistance & Capacitance Vessels .............................................................................................................................. 6
Systemic Circulation ....................................................................................................................................................... 6
Velocity & Flow of Blood ................................................................................................................................................ 7
Arterial Pressure ............................................................................................................................................................. 7
Gravity ................................................................................................................................................................................. 7
Bernoullis Principle ....................................................................................................................................................... 7
Auscultation ....................................................................................................................................................................... 7
Normal Blood Pressures ................................................................................................................................................ 7
The Microcirculation .......................................................................................................................................... 7
Filtration of Water ........................................................................................................................................................... 8
Flow Limited vs Diffusion Limited Exchange ...................................................................................................... 11
Activating Capillaries .................................................................................................................................................. 12
Venous Return ............................................................................................................................................................... 12
Venous Pressure in Head ........................................................................................................................................... 12
Air Embolism .................................................................................................................................................................. 12
Measuring Venous Pressure ..................................................................................................................................... 13
Lymphatics ........................................................................................................................................................... 13
Interstitial Fluid Volume ............................................................................................................................................ 13
Fluid Volumes ................................................................................................................................................................ 14
3.Dynamics of Blood Flow -
Intro
Flow created by:
o Pumping of heart
o Diastolic recoil
o Muscle pump
o -ve thorax pressure in resp
Resistance to flow:
o Diameter of vessels
o Viscosity
Flow regulated by:
o Local chemical
o General neural & humoral mechanisms
Vessels
Vascular Smooth Muscle
vital in regulating vessel diameter

contraction produced by myosin light chain mechanism
prolonged contraction determining tone produced by latch bridge mechanism
calcium effects on contraction:
o Ca influx via voltage gated Ca channel Ca [in] contraction
o Also Ca [in] Ca release from SR via Ca sparks Ca [in] which interacts with 1
subunit on Ca activated K channels in cell membrane (BK channels) BK opening fast K
efflux membrane potential shutting of voltage Ca channels relaxation
! neg feedback system for homeostasis
! sensitivity of 1 subunit to Ca sparks controls vascular tone
Arteries & Arterioles

Out in:
o Outer CT
o Adventitia
o External elastic lamina
o Middle layer smooth mm
o Media
o Intima:
! Internal elastic lamina
! Endothelium
Large diameter arteries = elastic tissue
Arterioles = elastic tissue; smooth muscle
Smooth mm in arterioles innervated:
o NA nerve fibres VCs
o Cholinergic fibres VD (only in some instances)
Capillaries
Arterioles metarterioles capillaries

Pre capillary sphincters
! not directly innervated BUT do respond to circulating VC substances
Capillary diameter
o 5um artery end
o 9um venous end
! when dilated allow rbc through in single file
capillary walls 1cell thick (1um)
transport across endothelium:
o junctions between cells:
! in general - permit molecules 10nm
! brain tighter junction
! intestine cytoplasm of cells themselves have fenestrations 20-100nm wide
! liver sinusoidal capillaries 600-3000nm
o active vesicular transport
pericytes:
o live around capillary ECs
o release vasoactive substances
o synthesise BM
o regulate flow inbetween ECs especially in presence of inflam
Lymphatics
many valves
no fenestrations
open junctions between ECs
A/V Anastomoses
seen in fingers, palms, ear lobes

thick muscular walls
innervated ++ by VC nerve fibers
Venules & Veins
little smooth mm
! but NA nerves and circulating VCs (eg endothelins) VC
valves from folded intima of limb veins
! not present in v small veins, great veins, veins from brain & viscera
Angiogenesis
VEGF vital
BioPhysics
Equations
Ohms:
Flow (mL/s), pressure (mmHg) , resistance (R unit):
Pressure
Flow
Shear stress = viscocity x shear rate

Velocity, flow, area:
velocity
Resistance
flow
Area
Poiseuille-Hagen Formula
R=
8 x viscocity x length
x r4
Reynolds Number:
Re = 2rvd
n
r = radius
v = velocity
d = density
n = viscocity
Law of laplace:
Tension = Pressure x radius
2xWall thickness
Or in a blood
vessel:
tension
Pressure
radius
pulse pressure = systolic diastolic pressure

mean pressure = diastolic pressure + 1/3 of pulse pressure
Flow, Pressure, Resistance

flow = pressure / resistance
Pressure = mean intraluminal pressure at arterial end pressure at venous end
Laminar Flow
Velocity is greatest in center of stream

Laminar flow occurs up to critical velocity turbulent flow
Probability of turbulence related to
o velocity
o diameter as will cause velocity
o viscosity eg anaemia
Re number = probability of turbulence
! <2000 = no turbulence
>3000 = nearly always turbulent
Shear Stress
Shear stress = viscosity x shear rate
shear stress marked change in gene expression by EC eg VCAM-1, TGF-B, endothelin 1
Average Velocity
velocity = flow / area of conduit

rules:
o velocity area
! works same in system of parallel tubes
Flow & Radius

Laminar Flow
poiseuille-Hagen Formula:
R=
8 x viscocity x length
x r4
! blood flow & resistance to radius 4
eg
o flow through vessel: doubled by 19% radius
o resistance in vessel: decr to 6% of original with radius x2
Turbulent Flow
equation:
density x length
x r5
Viscosity & Resistance

resistance to flow determined by:
o radius (most)
o viscosity
viscosity depends mostly on haematocrit ie % volume of blood occupied by rbcs
! also on composition of plasma & resistance of rbcs to deformation
in vivo effect of viscosity different to poiseuille-Hagen formula:
o large vessels haematocrit viscosity
o small vessels <100um haematocrit small effect as cells flow in single file through capillary
anyway
! haematocrit only effects resistance in extremes eg anaemia or polycythaemia
Critical Closing Pressure

ing pressure small blood vessel will get to a point where no blood flows even though pressure > 0
! = critical closing pressure
Law of Laplace
Tension in wall of cylinder is equal to the product of transmural pressure & the radius divided by wall
thickness:
Tension = Pressure x radius
Wall thickness
Transmural pressure = pressure inside cylinder pressure outside
! but pressure outside body is low so pressure inside can simply be used
law can be changed to:
Pressure = tension
Radius
radius of blood vessel, the tension required to balance distending pressure
demonstrates problems with dilated hearts:
o radius of vent chamber means tension required to generate any pressure
Resistance & Capacitance Vessels
veins normal state is collapsed

! large amount of blood added to veins before they distend & volume pressure
arterioles = resistance vessels
veins = capacitance vessels
Vasodilation/-constriction: - refers to arterioles ( ie chief site of vascular resistance) SVR
Venodilation/-constriction: - refers to veins ( ie the capacitance vessels) VR
distribution:
o 65% veins (55% in supine)
o 15% central blood volume (25% in supine) heart & lungs
o 13% arteries
o 2% arterioles
o 5% capillaries
Systemic Circulation
TA = total area
RR = relative
resistance
Velocity & Flow of Blood

proximal aorta flow:
o phasic forwards and backwards (too close aortic valve)
other vessels flow is continuous due to elastic recoil of vessels
! but still pulsatile otherwise gradual in resistance
Arterial Pressure
pulse pressure = systolic diastolic pressure
mean pressure = diastolic pressure + 1/3 of pulse pressure
Gravity
pressure in vessels below heart ed & above is ed

gravity = 0.77mmHg/cm difference
Bernoullis Principle
sum of the kinetic energy of flow and the potential energy is

constant:
o pressure drop due to energy lost when overcoming resistance is lost as heat
o pressure drop due to potential energy conversion to kinetic energy in narrow vessel is reversed
when narrowing passed
! = greater velocity of flow ed lateral pressure distending its walls
! narrowed vessels velocity distending pressure
! narrowed atherosclerotic plaque is self sustaining
Auscultation
Kororkoff sounds produced by turbulent flow caused by narrowing of vessel >critical velocity
Diastolic pressure correlates best when sound becomes muffled in
o Post exercise
o Children
o AR
o Hyperthyroid
! otherwise when turbulent flow ceased.
Cuff near systolic pressure only intermittent high velocity jets through vessel at peak systole
Cuff near diastolic pressure = constricted vessel continuous turbulent flow
Normal Blood Pressures
Sleep 20mmHg
Pulse pressure s with age diastolic pressure s at middle age as arteries become stiff
The Microcirculation
By definition =
o Smallest arterioles
o Metarterioles
o Precapillary sphincters
o Capillaries
o Small venules
~25 billion capillaries in body
many are closed for long periods ie skeletal mm
! ~1/4 open at ret ie recruited when needed
skin has AV shunts for specialised functions (temp control)
! does not contribute to gas exchange and waste product removal
cap flow is intermittent due to regular contraction/relax of precapillary sphincters
! called vasomotion
! local hypoxia = most impt factor spincter relaxation
Function of Microcirculation
systemic capillaries contain ~5% blood volume in close contact with tissue cells function =
o transfer/exchange of water, electrolytes, gases, nutrients, wastes & heat
Capillary Pressure & Flow
Capillaries are short but blood moves v slow as large cross sectional area
! transit time art to ven end = 1-2sec
Equilibration with Interstitial Fluid
Transfer/exchange across capillary wall:
o Non water movement:
! Electrolytes & other small molecules cross via pores & intracellular gaps
! Lipid soluble (incl O2 & CO2) cross directly through thin endothelium
! Proteins & other larger molecules diff to cross membrane:
Pinocytosis OR
Endo/exocytosis
o Water:
! Diffusion:
Large amount (~80 000 litres/day) ie much larger than daily CO of ~8000/d
Occurs in both directions & does not = any net water movement across cap wall
! cos in norm conditions no osmotic gradient across cap wall
! Filtration see notes below
Filtration of Water
Separate to diffusion being actually ultrafiltration (plasma proteins do not cross)
Ultrafiltration occurs due to balance of:
o Hydrostatic pressure
o Osmotic pressure
! aka Starling forces & net movmt of water can be predicted using Starlings equation
Depends on balance:
o Hydrostatic pressure gradient
! = Pressure in capillary ( Pc) pressure in interstitial fluid ( Pi)
o Osmotic pressure gradient:
! = osmotic pressure in capillary ( c) osmotic pressure of interstitial fluid (I)
pressures vary:
o by tissue
o along length of capillary - NET movement:
! outward - arterial end
! inward venous end
Net driving pressure = [ (Pc Pi) - (c - I ) ]
2 more additional factors added:
o reflection coefficient () = leakiness for proteins
o filtration coefficient (K) = leakiness for water
= K x [(Pc Pi) - (c - I ) ]
Reflection coefficient ()
= correction factor applies to measured oncotic pressure gradient across cap wall
needed to correct equation:
o because of small leakage of proteins I = would otherwise be artificially high
o not all protein present in capillary is effective at exerting an oncotic pressure c would
otherwise be artificially high
! both factors actual oncotic pressure gradient
value is from 0 to 1 depending on tissue:
o CSF & Kidney (glomerular filtrate): both have v low proteins = close to 1
o Liver: = closer to 0 because of:
! v high protein amount
! proteins pass through very leaky hepatic sinusoids easily
Filtration Coefficient (K)
net fluid flux due to filtration is proportional to NET driving pressure
K = constant of proportionality in the flux equation
K depends on 2 components:
o Area of capillary walls
o Permeability of capillary walls to water (aka hydraulic conductivity)
! K = area x hydraulic conductivity
Eg leaky capillary would have high K
NET Fluid Flux
Complete equation:
= K x P
= K x [Phydrostatic - . ]
= K x [(Pc Pi) - (c - I ) ]
Typical Starling Values (CVS Capillaries)
Arteriolar end
Pc
Pi
(Ptotal)
c
I
(total)
net filtration P
25mmHg
0
(25)
20
5
(20)
+10
venous end
10
0
(10)
20
5
(20)
-5
Along length of cap only pressure that drops is hydrostatic pressure

Body as a whole:
o NET ultrafilration of ~ 20ml/min
! 18ml/min reabsorbed by capillaries
! 2ml/min removed by lymph ie 2-4litres /day into lymph
Starling equation limited value in practise as needs measurement of 6 unknowns
more useful to describe NET fluid movement in diff capillary beds
Kidney (glomerulus) Starling Forces:
o In Glomerulus (ie GFR) NET excess ~ 180litres/day
! different lies in reabsorption in kidney tubules
Glomerula specifics:
o High K
o High ~1.0
o Pc is high and does not drop much along the length of the capillary.
o c increases along the length of the capillary ( large fluid loss (concentration proteins) + high c
initially).
! This ed capillary oncotic pressure is important for the reabsorption of water into the
proximal tubule from the peritubular capillaries
o = NET outward filtration pressure along whole length of glom capillary
Aff. Art end
Eff art end
PGC
PBC
GC
BC
45mmHg
10
20
0
45
10
35
0
Net filtration P
15
(GC = glomerular capillary

BC = Bowmans capsule
Hhydrostatic pressure in the glomerular capillary is affected by the balance b/w afferent and efferent arteriolar tone.)
GFR = K x ( PGC PBC - GC )

Cerebral Microcirculation
most body capillaries are
o permeable to low mw solutes (ie Na & Cl)
o impermeable to high mw solutes (aka proteins) (depending on their ).
! it is the large protein solutes which exert an osmotic force across cap wall
! ie there is a differential inside to outside capillary
in cerebral capillaries the cap membrane:
o relatively impermeable to all solutes incl low mw solutes eg Na & Cl
low mw solutes exert an osmotic force across cerebral capillary membrane (ie BBB)
starling forces in cerebral caps =
o hydrostatic pressure
o osmotic pressure (not oncotic) due to effective solutes
oncotic pressure is small in comparison to huge osmotic pressure exerted by low mw solutes
! because number and not size is important
! aka colligative properties
! other colligative properties = SVp depression, boiling point elevation, freezing
point depression
small leak of these solutes can also be accounted for with a reflection coefficient
! same as for plasma protein elsewhere
1 mOsmole osmotic pressure gradient blood:brain interstitial fluid force 17-20mmHg
3.Dynamics of Blood Flow - 10
! small change in plasma tonicity has marked effect on cerebral volume
(tonicity = effective osmolality ie osmoles effective at exerting an osmotic pressure across membrane in
question)
Pulmonary Microcirculation
main function is gas exchange
features that assist with gas exchange:
o pulmon capillaries & alveoli have v thin walls
o large SA for exchange: capillaries in the alveolar walls are seen as a continuous film of flow
o
o low pressure pulmon circuit very low resistance (but pressure sufficient to perfuse apical lung
(West zone 2)
Starling forces in the lung:
Arteriolar end
Pc
Pi
c
I
13 mmHg
0 slight neg
25
17
venous end
6
0 neg
25
17
oncotic gradient:
o reflection coefficient ()is low = ~0.5
o allowing for NET oncotic gradient is small favour reabsorption
hydrostatic pressure:
o capillaries in lung
! = intra-alveolar vessels:
cap vessel pressure exposed to alveolar pressure
! = average of zero
! varies with gravity:
pressure @base : apex
pressure diff equivalent to height static water column from base to apex ( ~23mmHg)
! quickly affected by change in pulmon artery pressure & LAP
! not much buffering
o alveolar interstitium:
! slight ve pressures
! closer to hilum: interstitial pressure ingly negative
! this favours flow of fluid from interstitium into pulmon lymphatics
overall under norm conditions small NET outward flow of fluid
! this = pulmonary lymph flow = ~10-20ml/hr
NET fluid movement outward (into interstitium) should be bad for gas exchange ie pulmon oedema
! but mechanisms exist to prevent it (see resp notes 4 blood flow end of section)
Flow Limited vs Diffusion Limited Exchange

flow limited exchange =
o small molecules equilibrate near arteriolar end
! to total diffusion need to flow
diffusion limited exchange =
o substances dont reach equilibrium during passage through tissues
! flow will not exchange
Y = diffusion limited
X = flow limited exchange
Activating Capillaries
capillaries activate by VD of precapillary sphincters & metaarterioles:
o VD metabolites
o permeability noxious stimuli. Effected by:
! substance P
! bradykinin & histamine
Venous Pressure & Flow

CVP ~5mmHg
Gravity has greater effect on venous pressure than art pressure
Velocity of flow s as blood from venules to greater veins
! av 10cm/sec
Venous Return
Aided by:
o Inspiration
! intrathoracic pressure -2.5 to -6 mmHg
! CVP inspiration 2mmHg; expiration 6mmHg
! this drop aids venous return
! diaphragm descends intrabdo pressure VR as valves prevent backflow to LL
o ventricular ejection pulling of tricuspid valve down sucking of blood into RA
! venous flow is pulsatile near heart
! 1 peak = vent systole
2nd peak = rapid vent filling in early diastole
o Muscle pump:
! Quiet standing venous pressure @ ankle 80-90mmHg
! Contractions of leg mm pressure @ ankle 30mmHg
! even if incompetent valves still see benefit as resistance less in larger veins ie
proximally
Venous Pressure in Head

Dural sinuses have rigid walls no critical closing pressure
In standing pressure in them is subatmospheric
! pressure to distance above collapsed neck veins (top head ~ -10mmHg)
Air Embolism
Disturbs forward movement of blood as air is compressible

Surface tension of air bubble resistance to flow
Rx hyperbaric oxygen - s size of gas emboli
5-100mls lethal
Measuring Venous Pressure

mean pressure vein in ACF = 7.1; CVP ~5mmHg
convert mm Saline to mm Hg by dividing by 13.6
CVP:
o Increased by:
! Positive pressure breathing
! Straining
! Expansion of blood volume
! Heart failure
o Decreased:
! -ve pressure breathing
! shock
Lymphatics
in capillaries normally efflux > influx
remainder into lymph
24hr lymph flow/day 2-4L
lymph divided:
o initial lymphatics:
! no valves or smooth mm
! in intestine & skeletal mm
! fluid enters through loose junctions between ECs
! flow created by mm pump & artery pulsations
o collecting lymphatics:
! have valves & smooth mm
! have own peristalsis
! flow also aided by:
mm pump
-ve intrathoracic pressure inspiration
suction effect high velocity blood in veins which lymph drains into
25-50% of total circulating plasma protein filtered and returned to blood via lymph
Interstitial Fluid Volume
cause of ed volume & oedema:

o filtration pressure:
! venular constriction
! ed venous pressure ie
failure,
incompetent valves,
vein obstruction,
hypervoleamia salt & water retention
o osmotic pressure gradient
! plasma protein cirrhosis, nephrosis
! accumulation osmotically active substance in interstitium
o cap permeability:
! substance P
! histamine, kinins
o inadequate lymph flow
Exercising mm:
o cap pressure so higher than oncotic pressure through whole cap efflux
o osmotically active metabolite accumulates in interstitium efflux
o lymph flow cannot keep up
! mm volume may up 25%
Fluid Volumes
see chp 1 physiology notes
4.CVS Regulation
Table of Contents
Introduction .......................................................................................................................................................... 2
Physics Reminder ............................................................................................................................................................ 2
Local Control of CVS ............................................................................................................................................ 2
Vasodilator Metabolites ................................................................................................................................................ 2
Local Vasoconstriction ................................................................................................................................................... 3
Other Substances Effecting VD/VC ............................................................................................................................. 3
Neural Control of CVS ......................................................................................................................................... 3
Receptors & The Afferent Limb ...................................................................................................................... 3
Arterial Baroreceptors .................................................................................................................................................. 3
Cardiopulmonary Receptors ........................................................................................................................................ 5
Periph Chemoreceptor Reflex ..................................................................................................................................... 6
Other Receptors ............................................................................................................................................................... 6
Central Integration .............................................................................................................................................. 7
Central Centres ................................................................................................................................................................. 7
Medulla & Spinal Cord Cells ......................................................................................................................................... 7
1. Central Sympathetic Output .................................................................................................................................... 7
2. Central Parasympathetic Output ........................................................................................................................... 8
3. Nucleus Tractus Solitarius (NTS) ........................................................................................................................... 8
4. Cerebellum .................................................................................................................................................................... 9
5. Midbrain Periaqueductal Grey (PAG) .................................................................................................................. 9
6. Hypothalamus .............................................................................................................................................................. 9
Efferent Limb ...................................................................................................................................................... 10
Innervation of Blood Vessels .................................................................................................................................... 10
Neural Regulatory Mechanisms ............................................................................................................................... 10
Output Effects ................................................................................................................................................................. 10
Balance of Output ......................................................................................................................................................... 11
Summary Factors Effecting HR ...................................................................................................................... 11
Direct Effects on RVLM ..................................................................................................................................... 11
Valsalva Manoeuvre .......................................................................................................................................... 11
Abnormal Valsalvas .................................................................................................................................................... 13
Substances Released from Endothelium ................................................................................................... 14
Prostacyclin & Thromboxane A2 ............................................................................................................................. 14
Nitric Oxide ..................................................................................................................................................................... 15
Endothelin ....................................................................................................................................................................... 15
Other Functions of Endothelins ............................................................................................................................... 16
Systemic Regulation by Hormones .............................................................................................................. 16
Kinins ................................................................................................................................................................................ 16
Natriuretic Hormones ................................................................................................................................................. 16
Circulating VCs ............................................................................................................................................................... 17
4.CVS Regulation -
Introduction
Different levels of control of circ:
o Local control caters for specific organs
o Central control caters for whole body putting brain first
o Systemic Regulation by Hormones
Generally there is a hierarchy in these control levels
Physics Reminder
P
Q = R
( Ohms law )
Thus, for the whole circulation: CO =
(MAP - RAP )
SVR
for a specific organ (simple): Qorgan =
( Pa - Pv )
Rorgan
where Pa = MAP
( Pa - larger of Pv/3rd P)
for an organ where a Starling resistor applies: Qorgan =
Rorgan
The different mechanisms that control the circulation (whether whole body or individual organ) will
influence either P or R .
Remember factors that determine resistance (R) :
8L
From Poiseuilles flow equation, resistance: R = r4
= viscosity
L = length
r = radius of tube
NB power of 4 effect
! above applies for laminar flow in rigid tubes, be it blood, air, urine etc
Local Control of CVS

Aka autoregulation
Autoregulation consists of:
o Pressure autoreg:
! pressure distension of walls contraction of vasc smooth mm
! Law of Laplace wall tension distending pressure x radius
! maintenance of a specific wall tension: if pressure s requires a in radius
o Metabolic reg:
! blood flow Metabolites accumulate VD
! blood flow metabolite VC
Vasodilator Metabolites
causes of VD:
o O2 tension:
! hypoxia inducible factor 1 (HIF 1) VD gene expression
o pH
o pCO2 most pronounced in brain & skin
o temp
o k+ - causes hyperpolarization of smooth mm VD
o lactate
o adenosine in cardiac muscle only
! also inhibits NA release
4.CVS Regulation -
Local Vasoconstriction
causes of VC:
o injury to vessels 2nd to local release of serotonin from activated platelets
! veins constrict weakest as least smooth mm
o temp
Other Substances Effecting VD/VC

independent VDs:
o Adenosine
o ANP
o Histamine via H1 & H2
o Bradykinin
o Vasoactive intestinal peptide (VIP)
Independent VCs:
o Ach
o Substance P
Neural Control of CVS
Receptors & The Afferent Limb

Various variables are measured:
o Baroreceptors - Arterial bp
o Cardiopulmonary Receptors
o Periph chemoreceptors temp & chemical changes
o Others:
! Periph nociceptors pain
! Stretch lung receptors
! Activity - mechanoreceptors
Arterial Baroreceptors
= stretch receptors
found in:
o carotid sinus
! just off origin of internal carotid in adventitia
! carotid sinus nerve (branch of IX)
o aortic arch
4.CVS Regulation -
! aortic depressor nerve (branch of X)
! transverse aortic arch
! in adventitia
stretch stimulates receptors impulse to medulla release +ve glutamate onto nucleus of the tractus
solitarius (NTS).
NTS
o +ve Glutamate on caudal ventrolateral medulla (CVLM) PNS output
o ve GABA on RVLM SNS output
! baroreceptor symp & parasymp output ie CO & SVR bp
baroreceptors much better at vasoC than venoC
Firing Activity
Receptors sensitivity to pulsatile pressure than constant pressure
! drop in pulse pressure (ie narrowing) with no change in MAP s rate of receptor discharge
bp & hR
MAP thresholds for firing: 60mmHg to 200mmHg

Each baroreceptor neuron fires over a narrow pressure range but collectively cover wide range:
o C fibres higher threshold
o Myelinated A fibres = lower threshold ie more sensitive to low pressures
Receptor Resetting
Baroreceptor mechanism is reset in chronic HTN
?due to opening of K channels return of membrane potential to baseline
Resetting occurs rapidly in animals and is rapidly reversible
! thought baroreceptor reflex responsible for changes in HR and bp on lying/standing
! opposite to long term regulation of bp = balance of fluid in/out ie volume regulation
! shows importance of renal function in bp control
If remove baroreceptors:
o Rapid rise in bp but mean pressure then drifts back to norm
4.CVS Regulation -
Cardiopulmonary Receptors
3 main groups:
o Veno-Atrial Stretch Receptors
! aka low P or volume receptors
! Myelinated
! vagal
o Cardiac mechanoreceptors
! Unmyelinated
! Vagal & symp
o Central Chemosensitive fibres:
! Vagal & symp
If stimulated as a group:
o NET inhibitory effect: reflex brady & vasoD bp
! = Bezold Jarisch reflex may see in Acute MI
If stim individually == diff CVS effects
Veno-Atrial Stretch Receptors
Located in endocardium @ junction vena cava & pulmon vein with atrium
Two types:
o A
! discharge in atrial systole ie with a wave
o B
! d/c in late diastole/atrial filling ie with v wave
! give info to CNS of degree of distension of atrial walls ie CVP
stim of both receptors
o immediate: HR via SNS to SAN
o late: urine volume & Na excretion bp
! via Bainbridge effect:
o ADH
o renal SNS activity ie RAAS
o atrial ANP production
! main function of Veno-Atrial stretch Rs = regulate cardiac size when CVP high
Cardiac Mechanoreceptors
=unmyelinated vagal & symp receptors
fine network endocardium of:
o RA & LA only some fire at height of atrial filling with insp
o LV fire during vent contraction
Combined effect is HR & vasoD
! similar function to arterial baroreceptors
! loss of afferent input from either art baroreceptors or cardiac mechanorecptors no sig effect on
bp BUT loss of BOTH sustained bp
vasovagal syncope:
o VR and dehydration baroreceptors symp HR & SV vigorous vent contractions
against empty ventricle activation vent baroreceptor further bp & SV syncope
Central Chemosensitive Fibres
vagal & sympathetic
in heart
stim by products from ischaemic heart mm
symp ones implicated in pain cardiac ischaemia
convergence with somatic pathways in spinothalamic tract explains referred pain into neck/arms
4.CVS Regulation -
Periph Chemoreceptor Reflex

found in carotid & aortic bodies
very important in respiration (same receptors)
have v high rate flow
activated by
o PaO2
o PaCO2
o pH only in carotid bodies
o blood flow to receptors:
! stagnant flow 2nd to MAP
result of activation:
o resp: ventilation main
o direct CVS effects = bp & HR
! but indirect NET effect is that the HR is offset by ventilatory stim ie
o stim of insp neurons
! inhibits central PNS cells
o stim of lung stretch receptors
! HR
o Mayer waves :
! Slow reg oscillations (every 20-40secs) in blood pressure during hypotension
! Created as blood flow hypoxia receptor d/c bp blood flow receptor
d/c and cycle
periph chemoreceptors vital in correcting MAPs <60mmHg

(! NB arterial baroreceptors dont fire <60mmHg)
periph chemoreceptor action explains clinical response to bp of tachypnoea & tachycardia
Other Receptors
Many other sensations reflex CVS responses:

o Somatic pain bp + HR
o Severe visceral pain HR + bp
o Bladder distension HR + bp
o Cold bp
o Threatening sight/sound HR, contractility, SVR
o Facial nerve stimulation with cold water HR + SVR
! = diving response - sometimes used to try terminate SVTs
4.CVS Regulation -
Central Integration
+glu CVLM para ns

-ve GABA RVLM symp ns
Central Centres
Central neuronal axis group of cells in various locations with a lot if integrated central processing:
o Medulla most impt. Where vasomotor centre exists
o NTS
o Cerebellum
o Cerebral Cortex
o Midbrain Periaqueductal grey (PAG)
o Hypothalamus
o Limbic system
! all control autonomic efferent limb
Afferent limb fed back via NTS
Central processing of afferent info in medulla & higher centres modulation of medullary SNS &
PNS neurons altered balance SNS vs PNS autonomic output
Medulla & Spinal Cord Cells
In medulla:
o Premotor symp nerves
o Preganglionic parasymp nerves
o Medullary interneurons
In spinal cord (intermediolateral column):
o Preganglionic symp neurons
1. Central Sympathetic Output

Premotor Sympathetic Nerves
5 groups of cells which innervate preganglionic outflow to all symp ganglia in medulla:
o RVLM most impt in control of MAP aka vasomotor area
o RVMM (rostral ventromedial medulla)
4.CVS Regulation -
o Caudal raphe nuclei
o Paraventricular nucleus in hypothalamus
o A5 noradrenergic cell in caudal ventrlateral pons
Rostral ventrolateral medulla (RVLM)
o Are +ve (excitatory) premotor fibres
o Output to symp preganglionic cells in spinal column intermediolateral gray column (IML)
o RVLM neurons are:
! tonically active
! responsible for resting SNS output to CVS
! maintain CO & SVR at rest
o Afferent input into RVLM arrive from:
! Afferents from baroreceptors -ve on RVLM
! Carotid & aortic chemoreceptors +ve on RVLM
! Direct +ve stimulation by Co2, hypoxia
! Area postrema (lacks bbb):
Vascular area on dorsum of medulla
Circulating angiotensin can directly stim RVLM MAP
! Other input:
Cerebral cortex:
o Limbic cortex via hypothalamus bp & HR caused by emotions
Reticular formation - pain +ve on RVLM
Somatic afferents somatosympathetic reflex from exercising mm +ve on RVLM
Sympathetic Preganglionic Cells in Spinal Cord
Most symp preganglionic cells are in IML columns of Tx & Upper Lx segments
Ach = neuro-transmitted at ganglia
Have specificity for diff organ circulations
! but symp ganglia & adrenal medullar are innervated from multiple cord segments
2. Central Parasympathetic Output

Situated in
o nucleus ambiguous (NA)
o dorsal motor nucleus of vagus nerve
stim:
o baroreceptor via NTS discharge in synchrony with cardiac cycle
o direct input from medullary inspiratory neurons output of NA tachycardia of inspiration
(sinus arrhythmia)
3. Nucleus Tractus Solitarius (NTS)

located in dorsomedial medulla
= principle site of termination of:
o primary CVS afferents CN IX (carotid sinus) & X (aortic arch))
o 2nd order afferents from other visceral & somatic receptors
also receives input from higher centres which likely modulates output response
= a gateway & relay station to:
o spinal cord
o medulla
o hypothalamus
o cerebral cortex
Role:
o If ablated sustained HTN
o ed Afferent baroreceptor
! stim NA PNS output to heart
4.CVS Regulation -
! stim CVLM inhibition of RVLM SNS output to heart, kidney, vessels & adrenal
medulla
4. Cerebellum
involved in regulation of CVS response to mm & joint activities in exercise
input from:
o cortex
o brainstem via extrapyramidal tracts & vestibular system
o ascending pathways via spinocerebellar tracts (dorsal & ventral)
5. Midbrain Periaqueductal Grey (PAG)
roles in :
o antinociception & reaction to threat
o defence reaction ie bp, skeletal mm vasoD & renal vasoC
different areas of PAG have diff actions:
o lateral pressure response ie vasoC
o ventrolateral depressor effects ie vasoD
connects with RVLM
6. Hypothalamus
imp in general homeostasis

discrete cell groups:
o defense area (short term control)
! ant perifornical region
! HR, CO, bp, vasoD skeletal mm, vasoC GIT & renal vessels, rage/fear behaviour
! inhibits the baroreflex at NTS, inhibits vagal output, stim the RVLM SNS>PNS output
o depressor area: (short term control)
! anterior hypothalamus
! effects similar to baroreflex
o supraoptic & paraventricular nuclei: (longer term control)
! ant hypothalamus
! produce ADH in response to:
stim of local osmoreceptors
input from art baroreflex
o temp regulating area:
! ant hypothalamus
! core temp vasoC outflow to skin & sweating vasoD & heat loss
7. Limbic System
consists of:
o ant cingulate
o post orbital gyrus
o hippocampus
o amygdala
amygdala stimulates hypothalamus defence area fear/rage
limbic may be responsible for playing dead behaviour in animals in danger
8. Cerebral Cortex
role in rapid CVS changes at beginning of ex ie PNS output
connections into:
o amygdala
o hypothalamus
o RVLM
o NTS
4.CVS Regulation -
Efferent Limb
Pathway consists of:
o Vagus
o SNS
o Hormones:
! Adrenaline & Noradrenaline
! ADH
! Renin, angiotensin
! Atrial natriuretic factor (ANF)
Effectors:
o Heart
o Blood veseels
o Kidneys
o Thirst/water intake
Innervation of Blood Vessels

Symph NA fibres all vessels VC
! have background tonic activity
Symp cholinergic fibres skeletal muscle VD
! no tonic activity
In most tissues VD is mediated by symp NA activity
! in skeletal mm active VD by symp cholinergic system
Neural Regulatory Mechanisms

All vessels receive motor fibres from SNS except capillaries & venules
Fibres to resistance vessels (arterioles) regulate flow & resistance (pressure)
Fibres to capacitance vessels vary volume of blood stored
Output Effects
SNS & Adrenaline & NA

Heart: contractility & HR CO
Arterioles: vasoC SVR
Veins: venoC VR CO (switch volume to art side of circuit)
SNS:
o renin release from juxtaglomerular apparatus (JGA) of kidney renin-angiotensin-aldosterone
activation H20 & Salt retention
o angiotensin 2:
! potent vasoC:
direct on periph vessels
indirect SNS via area postrema of medulla
! stimulates thirst & ADH H20 retention MAP
Vagal
effects limited to heart
mainly AVN/SAN/atria
ADH
made in hypothalamus by supra-optic & paraventricular nuclei
stored & released from ost pituitary
effects:
o H20 retention
o Arteriolar constriction
ANF
Released from atria in response to distension/stretch
4.CVS Regulation - 10
Effects = renal salt & H20 excretion (Bainbridge response)
Balance of Output
tonic activity:
o mild amount symp
o larger amount parasymp
! if both blocked HR ~100/min
Summary Factors Effecting HR

In general stim which HR also bp except:
o Atrial stretch receptor bp & HR
o ICP bp & HR
HR by:
o arterial baroreceptor activity
o atrial stretch receptor activity
o inspiration inhibition of nucleus ambigious PNS:SNS output
o excitement, anger pain
o hypoxia
o exercise
o thyroid hormones
o fever
HR by:
o arterial baroreceptors
o expiration
o fear, grief
o ICP
Direct Effects on RVLM
Cushing Reflex
ICP blood supply to RVLM local hypoxia and hypercapnia RVLM d/c bp restores
blood flow to medulla
in bp baroreceptor d/c HR which masks expected HR
in bp to ICP
! = Cushing reflex
Hypercapnia
PaCo2
periph & central actions cancel each other so
o RVLM d/c (HR, VC)
no VD or VC with slow rise in bp via HR effect
o direct peripheral VD
moderate RR PaCo2 cutaneous & cerebral VC
! little change in bp
Valsalva Manoeuvre
= forced expiration against closed airway (glottis, mouth, nose, ETT doesnt matter)
standardised valsalva = blowing into mercury column & holding a pressure of 40mmHg for 10-15secs
clinical use testing baroreflex & autonomic ns:
o autonomic function eg diabetes
o reversal of SVT
o Ax of cardiac murmurs:
! loudness in HOCM & MV prolapse
! loudness all other murmurs
Phases of Valsalva
defining feature is intrathoracic pressure (ITP)
phase 1:
o small brief bp at start of straining:
! 2 reasons:
ITP squeezes intrapulmonary vessels VR to L heart SV & CO brief
small MAP
ITP transmitted onto aorta
o HR unchanged
Phase 2:
o Early phase:
! Dropping bp: VR due to ongoing ITP & ing CO
o Middle phase:
! HR:
bp is sensed by baroreceptors afferent activity SNS & PNS HR &
contractility & SVR
! CO & SVR help to counteract effect of VR and defend bp
o Late phase: In normal healthy: MAP usually rises > baseline due to alpha adrenergic activation
o Pulse pressure narrows through phase due to SVR via SNS activity diastolic bp
Phase 3:
o Starts at cessation of strain
o Small bp immediately
o = reverse of phase 1 mechanisms ie squeeze on intrapulmonary vessels VR & ITP on
aorta
o because of briefness of phase HR remains unchanged before starting to fall
Phase 4:
o Overshoot of bp:
! Return of blood to L heart restoration of CO
! But now full CO pumping into vasculature still vasoC bp
o HR:
! bp sensed by baroreceptors afferent firing PNS & SNS HR (to lower than
baseline) & SVR
it is HR of phase 4 which is exploited to attempt SVT termination
Valsalva Ratio
= way to characterise/quantify Valsalva Response
2 way of calculation:
o ECG ratio between
! Longest R-R interval in phase 4
! Shortest R-R interval in phase 2
o Ratio between max HR phase 2 & min HR phase 4
HR changes are secondary response to valsalva via baroreflex
Norm valsalva ratio = >1.5
Causing of ing ratio (ie baroreflex responsive):
o Ageing
o Diabetes
o disease
Abnormal Valsalvas
Square Wave Response

see in heart failure
chars:
o elevated bp throughout phase 2
o no reactive bp in phase 4
o HR remains constant
Caused by ed pulmon blood volume acts as reservoir that maintains LV filling during phase 2
! ie like an extension of bp mechanism of phase 1
Beta Blocked Response

HR remains constant in phase 2
Phase 4:
o Much smaller overshoot
o Quicker recovery
! because of lack of HR changes
! if gave atropine (ie HR) recovery time would lengthen

! ie bp here solely due to VR CO (without HR changes as well)
Alpha Blocked Response
Chars:
o Lower bp in late phase 2 lack of SVR due to no receptor action
o Larger early phase 2 bp drop ed cardiac, periph SNS & central SNS compensatory output
which still present when come to phase 4 ed overshoot
o ed bp overshoot in phase 4
! size of response depends on HR
o HR responses intact
Caused by lack of SVR in phase 2: attempting to attenuate bp from CO
Labetalol Effect
= mixed beta-alpha blocker
see:
o dramatic size phase 4
! compared with pure alpha blocker
! by blocking HR ie B blocking effects predominate over alpha effects
o late phase 2 alpha blocking effects still occur (ie bp) but less so
! propranolol weak a antagonist
Autonomic Dysfunction Response
Excessive bp in phase 2
Absence of overshoot in phase 4
Bradycardia in phase 4
Substances Released from Endothelium

Prostacyclin & Thromboxane A2
prostacyclin:
o from ECs
o inhibit aggregation platelet
o VD
thromboxane :
o from Platelets
o platelet aggregation
o VC
Balance thromboxane & prostacyclin shifted by aspirin
o Aspirin irreversible inhibition of COX by acetylating a serine residue in active site
o ECs can remake prostacyclin in hours
o Platelets can never thus need new platelets in circ before TxA2 rises again
! half life ~4days
Nitric Oxide
Aka Endothelium derived relaxation factor (EDRF)
NO from arginine by NO synthase (NOS)
3 forms of NOS
o 1 nervous system
o 2 MP & other immune cells
o 3 in ECs
NOS is activated by agents which
o Ca [in] incl Ach & bradykinin
o products of platelet activation on uninjured ECs
NOS keeps patent vessels dilated
if EC injured: platelet activation marked VC
NO formed in EC then diffuses into vasc smooth mm activates guanylyl cyclase cGMP VD
! GTN acts in same way
Other roles of NO:
o tonic release important mediator of bp
o vascular remodelling & angiogenesis
o penile erection Viagra slows breakdown of cGMP
o impt in brain function
o antimicrobial & cytotoxic effects in inflam cells
NO inactivated by Hb
VCs of vessels have there effect ed by also causing NO release less VC
! eg bradykinin, VIP etc
Endothelin
Endothlin 1 =
o one of most potent VCs isolated
o in ECs, brain & kidneys
Also
o ET-2
! In kidney & intestine
o ET-3
! As ET-2 and also in blood & high amounts in brain
endothelin-1 gene big endothelin-1 endothelin -1
! ECs create prohormone
! endothelin converting enzyme
products act mostly locally & paracrine

! but some big endothelin & endothelin-1 released into blood
receptors coupled to phospholipase C via G proteins:
o ETA specific to ET-1 VC
o ETB
! responds to all ET 1-3
! may VD
! mediates developmental effects of endothelins
Regulation of Secretion
ET-1 not stored
Activators of gene:
o Angiotensin II
o Catecholamines
o Hypoxia
o Insulin
o HDL
o Shear stress
Inhibitors of gene:
o NO
o ANP
o PGE2
o Prostacyclin
Other Functions of Endothelins

Brain:
o Produced in early brain by neurons & astrocytes
o Role in regulation of transport across bbb.
Face prevent severe craniofacial abnormalities
Resp prevent resp failure
GI prevent Hirchsprung megacolon
Closure of ductus arteriosus
Systemic Regulation by Hormones

Circulating VD hormones:
o Kinins
o VIP
o ANP
Circulating VC hormones:
o Vasopressin
o Adrenaline
o NA
o Angiotensin II
Kinins
Actions resemble histamine:

o VC of visceral smooth mm
o VD of vasc smooth mm via NO bp
o cap permeability
o pain
o chemoattractant
created during:
o sweat & salivary secretion
o exocrine pancreas
! creates blood flow to active tissue
plasma kallikrein circulates in inactive form
tissue kallikrein located on apical cells involved in across cell electrolyte cell transport
bradykinin receptors coupled to G proteins

o B1 mediates pain
o B2 found many tissues. Very similar to H2 receptor
Natriuretic Hormones
Family:
o Atrial (ANP) - plasma
o Brain (BNP) - plasma
o C-type (CNP) acts paracrine
Hypervolaemia release
Action:
o Antagonise various VC agents bp
o ANP & BNP control fluid & electrolyte homeostasis via kidney
Circulating VCs
Vasopressin:
o Potent VC
o Also causes CO little change in bp
NA & Adrenaline:
o NA generalised VC action
o Adrenaline dilates vessels in skeletal mm & liver
Angiotensin II:
o Generalised VC
o Created by:
! Kidney releases renin rennin acts on angiotensinogen angiotensin I
! ACE acts on angiotensin I angiotensin II
o Renin secretion ed by
! bp
! volume of extracellular fluid
o action of Angiotensin II:
! water intake
! aldosterone release
! -ve feedback mech on renin
5.CVS Response to Function

Table of Contents
CVS Response to Changes in Posture ............................................................................................................ 2
Supine Erect ................................................................................................................................................................. 2
Shock ........................................................................................................................................................................ 3
Hypovolaemic Shock ....................................................................................................................................................... 3
Coordinated Response to Exercise ................................................................................................................ 5
Cardiac Output .................................................................................................................................................................. 5
Timing of Changes ........................................................................................................................................................... 5
CVS Changes ....................................................................................................................................................................... 5
Muscle Blood Flow ........................................................................................................................................................... 6
Blood Flow to Other Organs ......................................................................................................................................... 6
Summary CardioResp Control During Exercise ..................................................................................................... 6
Cardiac & Vascular Function Curves ......................................................................................................................... 7
CO = VR ................................................................................................................................................................................ 7
5.CVS Response to Function -
CVS Response to Changes in Posture

Supine Erect
CVS Challenges
in MAP: = due to CO due to VR
! venous pooling of blood in the lower extremities
effect occurs within seconds, but not immediately.
Hydrostatic effects on CPP:
o brain is ~ 30 cm higher than level of the heart in the erect position (as opposed to the supine)
o MAP at level of brain of ~ 22 mmHg
o effect = immediate.
! NB : MAP at brain level is offset by a similar:
o CVP venous side ( brain circulation is like an inverted U-tube) as well as on the
o CSF pressure.
! CPP is further augmented by an increase in VR from the brain to the heart in the erect position
Summary: the main challenge to the CVS ( and the brain circulation) is MAP caused mainly by VR
CO.
The CVS response
baroreceptor reflex mechanism:
o MAP sensed by carotid (mainly) and aortic baroreceptors traffic up to NTS via
medullary control centre SNS outflow and PNS outflow.
o The SNS outflow causes: [ remember: MAP (minus RAP) = CO x SVR ]
! [preload] peripheral venoC VR CO MAP
! [afterload] peripheral vasoC SVR MAP ( slight in SV due to afterload increase, but net
effect = MAP)
! cardiac contractility CO MAP

! Heart rate CO MAP
o
NB: Baroreflex vasoconstriction = more effective than venoconstriction to restore MAP
! (not to be confused with the vascular function curves where venoconstriction shifts the curve more up than what
vasoconstriction rotates it downwards)
Cerebral pressure autoregulation: a.k.a. the myogenic mechanism:

o effective at maintaining a constant cerebral blood flow within a MAP range of 50 150 mmHg.
o It effects this by changing the CVR.
o Onset is not immediate though.
MAP ( CVP or ICP)
CBF =
CVR
arterial baroreflex
pressure autoregulation
Activity: Mm pump further augments VR

! in conjunction with the one-way valves in the veins to prevents further venous pooling
Overview of CVS Response
Baroreceptor & cerebral autopressure reg effective in normal people to prevent fainting when standing
from supine.
If the arterial baroreflex is blunted, syncope
! eg elderly and diabetic autonomic neuropathy
The standardized valsalva test can be used to check the integrity of the baroreflex
Shock
Shock = inability of circulation to ensure adequate O2 delivery to the body tissues
Types:
hypovolaemic: - haemorrhagic ( loss of all blood components)
- loss of plasma ( burns)
- loss of fluids + electrolytes ( D+Vs, sweating etc)
- Internal ( 3rd spacing; eg ascitis, ileus, pancreatitis )
distributive:
- septic
- anaphylactic
- neurogenic ( including sympathectomy of a SAB)
- vasodilator drugs,
- acute adrenal insufficiency
cardiogenic:
- pump failure ( AMI)
- dysrhythmia ( tachy or brady)
- acute valvular dysfunction / rupture of ventricular wall or IV septum
Obstructive:
- tension pneumothorax
- massive pulmonary embolus
- pericardial disease ( tamponade, constriction)
DO2 = CO x CaO2
whenever discuss shock must consider all factors influencing CO:
o preload
o afterload
o conreactility
o HR
Hypovolaemic Shock
Very common
Causes both:
o CO via volume loss preload CO MAP
o CaO2
Resp Response:
Severe MAP hypoxia/hypercarbia/acidosis periph chemoreceptor stimulation
o SNS &
o hyperventilation
! in attempt to defend CaO2
CVS response
can be classified by time:
o Immediate:
! Sensors:
Arterial baroreflex [biggest response]
o aim to restore CO & MAP to normal
o MAP sensed in carotid & aortic baroreceptors
volume sensed by low pressure sensors of atria & large veins
hypoxia/hypercarbia/acidosis sensed by periph chemoreceptors
! Effect- predominantly of SNS & PNS via baroreceptors:
venoC: VR CO MAP
vasoC: SVR MAP
! widespread sparing only brain & heart
HR: CO & MAP
! in severe shock also see initial tachycardia transient brady back to tachy
! ?unmasking of vagal tone to help clotting
contractility: CO MAP
o Intermediate:
! Autotransfusion: Interstitial fluid move to intravascular (reversal of Starling forces)
! Up to 1000 ml fluid /hr can be moved intravascular via this mechanism.
! Mobilization of reserve volumes: splanchnic/liver mainly
! Decreased renal blood flow via MAP
(normally ~25% CO)
initial +ve effects:
o efferent vessels constricted > afferent
o renal plasma flow GFR filtration fraction ed
o ed Na retention
! UO which serves to preserve circulating volume
late ve effects:
o azotemia ie nitrogen waste products retained Urea & creat
o ARF
! Further redistribution of CO: muscle flow, skin flow
! Muscle pump activity of legs ( restlessness) VR
! ADH release ( from volume receptor input) water retention
! Thirst + other behavioural responses
! renin/angiotensin/aldosterone mechanism
! adrenaline from adrenal medulla
o Delayed (post haemorrhage) aim to restore components lost in blood
! 12 72 hrs :
plasma volume restored to normal
Albumin replaced rapidly from extravascular stores
! Days:
plasma proteins and enzymes: liver synthesis
! Days to weeks:
RBCs: EPO from kidneys
o reticulocytes peak day 10 days (norm ~1% retics in blood)
o mature RBCs back to normal 4 8 weeks.
Other: PLTs, WBCs
Can also be classified by severity:
o mod shock pulse pressure
! due to diastole caused by catecholamines ing vascular tone
! discharge baroreceptors symp tone VC & HR
o severe shock
! mean pressure
! tachybradytachy
! widespread VC spares only brain & heart vessels
! kidneys initial positive changes but then ve acute failure
Any inadequate perfusion to tissues
o anaerobic glycolysis lactic acid accumulation
o low/mod levels of lactic acid excellent fuel for heart/CVS system
! but tipping point acidosis
lactic acidosis
o myocardial contractility
o vascular response to catecholamines ie ed VD
o toxic to CNS coma
Coordinated Response to Exercise

muscular exercise requires 3 tasks from circulation:
o pulmon flow to enhance gas exchange
! ed RV output
o ed flow thru working mm
! ed LV output
! local vasoD
o maintain stable bp
! controlled vasoC in non active tissues
other issues need addressing:
o energy production & utilisation
o temp reg
o fluid shifts
o acid base changes/compensation
exercise can be
o static isometric
o dynamic isotonic
Cardiac Output
CO by x5 ie 5 l/min to 25 l/min
Heart = demand led pump:
o ed demand set by exercising mm effecting VR
VR caused by:
o venoC (VR)
o vasoD (SVR)
o mm pump of limb muscles (need intact venous valves)
o thoracic pump:
! ITP & abdo pressure with ed inspiration
! RR & depth of insp in exercise enhances effects
! -ve effects of expiration prevented by venous valves
o myocardial contractility
o HR
o diversion of blood from non active tissue (splachnic & renal circulations)
o local metabolites in exercising mm arteriolar dilation SVR CO blood flow to
exercising mm VR
Timing of Changes
start of exercise:
o sudden CO then gradual to steady state
sudden initial changes 2nd to:
o cortical activity (motor area)
o sensory nerve activity assoc with movement
o mm/thoracic pump VR
slow changes to steady state 2nd to:
o vasoD in mm
o redistribution of CO
o SNS
@end of exercise:
o abrupt CO
o exponential fall
CVS Changes
HR changes:
o linearly up to max ~200/min in young adult
o initially caused by vagal output
o later by ed SNS output
stroke volume:
o in non-linear way
o big in light/mod exercise; only small into severe exercise
o reasons for :
! VR & LVEDV
! contractility LVESV
blood pressure:
o SBP can rise to 190-225mmHg 2nd to ed CO
o DBP may increase slightly or even fall 2nd to SVR
! NET result pulse pressure x2-3
Baroreceptor reflex reset to higher level in severe exercise
Muscle Blood Flow
@rest:
o mm blood flow = 2-3ml/100g/min
! mediated by SNS constriction of arterioles
o ~20% of CO despite skeletal mm being ~40% of lean body mass
o precapillary sphincters closed diverts mm blood flow away from microcirculation to main
channels
@exercise see:
o relaxing of precapillary sphincters due to:
! PO2
! PCO2
! H
! temp
! K
! ADP in interstitial fluid
! result is total blood flow to max 50ml/100g/min ie x20 ~80-90% of CO
o diffusion of O2 into mm cell & total O2 uptake by up to x40:
! delivery O2
! R shift of OHDC
Static contraction: sig mm flow pressure in mm
Isotonic contraction good mm flow as flow occurs in relaxation
Blood Flow to Other Organs
coronary flow:
o must meet extra cardiac work
o mediated by:
! local metabolic autoreg
! circulating catecholamines stim B2
flow to GIT & kidney SNS activity shifts flow to exercising mm
skin flow to help with heat loss (SNS mediated)
cerebral flow:
o remains constant at all levels of ex ~50ml/100g/min
o but relatively much smaller % of ed CO
Summary CardioResp Control During Exercise

1st ventilation s keeping close proportion of:
VO2 + VCO2 PaO2 + PaCO2 = normal

near max intensity: VA rises > VO2 PaCO2
1 5-10seconds of exercise: HR 10-15/min due to vagal tone, then steady ing HR over 5-10min due
to SNS output
! initial tachy under central command
end of exercise: HR & VA fall sharply initially then more gradual
during exercise:
o baroreceptors reset to operate at higher bp ranges allowing ed HR, CO, MAP
! in moderate exercise this resetting compensates for SVR
in more strenuous exercise need SNS to compensate
o resp chemoreceptor reflexes also seem to reset:
! ed response to change in PaO2
! severe exercise: lactate (pH) additional stimulus
st
Cardiac & Vascular Function Curves

Exercise requires an CO & control of heart & vasculature
If isolated symp ns stim to heart (cardiac symp nerve stim):
o MAP CVP both of which favour ed SV (ie opposite of desired effect)
in exercise:
o [afterload] ed MAP minimised by VasoD of exercising mms
o [preload] CVP minimised by:
! periph venoC
! mm & thoracic pumps encouraging VR
in upright exercise SV can double due to:
o [preload] EDV (from CVP)
o [contractility] End systolic volume from EF via ed contractility
CO = VR
Ohms Law:
MSP - RAP
VR =
VVR
MSP = mean systemic pressure ~ 7mmHg

RAP ~2-3 mmHg
VVR = venous vascular resistance
! P ~ 5mmHg ie venous resistance is v low
c/f
LHCO =
MAP - RAP
SVR
LHCO = L heart CO
P ~ 88mHg
c/f
MPAP - LAP
RHCO =
PVR
RHCO = R heart CO
Mean Pulmonary artery P ~ 15mmHg
LAP 5mmHg
P ~10mHg
6.Circulation Through Regions

Table of Contents
Organ Supply & Consumption ........................................................................................................................ 2
Summary Highs & Lows .................................................................................................................................................................. 2
Autoregulation .................................................................................................................................................................. 3
Definition & Intro ............................................................................................................................................................................... 3
Cerebral Circulation ........................................................................................................................................... 4
Vessels ..................................................................................................................................................................................................... 4
Cerebral Blood Flow & Regulation ............................................................................................................................. 4
Special Tasks of Cerebral Circulation ........................................................................................................................................ 4
Adaptations to Meet Special Tasks ............................................................................................................................ 5
Structural Adaptations ..................................................................................................................................................................... 5
Functional Adaptations .................................................................................................................................................................... 5
Special Problems Facing Cerebral Circulation .................................................................................................................... 10
Measurement of Cerebral Circulation .................................................................................................................................... 10
Brain Metabolism ......................................................................................................................................................... 10
O2 Consumption .............................................................................................................................................................................. 10
Energy for Brain ............................................................................................................................................................................... 10
Glutamate & Ammonia Removal ............................................................................................................................................... 11
Spinal Cord Circulation .................................................................................................................................... 12
Arterial ................................................................................................................................................................................................. 12
Spinal Cord Perfusion Pressure ................................................................................................................................................ 14
Epidural Content .............................................................................................................................................................................. 15
Coronary Circulation ........................................................................................................................................ 16
Vessels & Valves ............................................................................................................................................................................... 16
Special Tasks ..................................................................................................................................................................................... 16
Structural Adaptations to Meet Tasks Required ................................................................................................................ 17
Functional Adaptation ................................................................................................................................................................... 17
Special Problems ............................................................................................................................................................................. 18
Measurement of Coronary Flow ............................................................................................................................................... 19
O2 Supply vs Demand of the Heart .......................................................................................................................................... 19
Renal Ciculation ................................................................................................................................................. 20
Hepatic Circulation ........................................................................................................................................... 20
Flow Pressures ................................................................................................................................................................................. 21
Hepatic Artery vs Portal Vein ..................................................................................................................................................... 21
Effect of Anaesthesia on Hepatic Blood Flow ...................................................................................................................... 22
Measurement .................................................................................................................................................................................... 23
Cutaneous Circulation ...................................................................................................................................... 24
Special Tasks ..................................................................................................................................................................................... 24
Structural Adaptation .................................................................................................................................................................... 24
Measurement of Skin Circulation ............................................................................................................................................. 25
Examples of Skin Reactions ........................................................................................................................................................ 25
Muscle Circulation ............................................................................................................................................. 27
Special tasks ....................................................................................................................................................................................... 27
Measurement .................................................................................................................................................................................... 28
Summary Relationship Between CO & Regional Circulations ............................................................ 28
6.Circulation through Regions - 1
Organ Supply & Consumption

Regional Blood Flows:
Brain: 50-54 ml/100g/min (whole brain) or ~ 750 ml/min or ~ 15% of CO

Note: flow to grey matter ~ 100ml/100g/min
( Note:Regional flows in cortex does change according to activity )
Coronary:84ml/100g/min or 200-250 ml/min or ~ 5% of CO
Renal: 400ml/100g/min or ~ 1200-1300 ml/min or ~ 25% CO ( 95% cortex , 5% medulla)
Hepatic: Total:57ml/100g/min or 1500 ml/min or ~ 30% CO
Hepatic artery: 300-500 ml/min
Portal vein: 1000-1200 ml/min
Resting skeletal muscle: 2-3 ml/100g/min or ~ 1000 ml/min or ~ 15-20% CO
Skin: ~15ml/100g/min (thermoneutral) ~ 300 ml/min or ~ 6% CO (variable)
Regional O2 consumptions:
Brain: (1400g) 3-3.5 mlO2/100g/min or ~ 50 mlO2/min

= ~ 20% of basal VO2
Coronary: (300g heart) 6-7 mlO2/100g/min or ~ 21 27 mlO2/min
= ~ 10% of whole body basal VO2
Renal: (300g) 6mlO2/100g/min or ~ 18mlO2/min
= ~ 7% of basal VO2
Hepatic: ( 2600g liver) 2mlO2/100g/min or ~ 50 mlO2/min
= ~ 20% of basal VO2
Resting muscle: ( 30kg) 0.2mlO2/100g/min or ~ 50mlO2/min
= 20% of basal VO2
Skin: (2-3kg) 0.3mlO2/100g/min or ~ 12mlO2/min
= ~ 4.3% of basal VO2
Summary Highs & Lows

Blood flow to:
o Max: Liver 1500ml/min
o Min: Heart 250
A/V O2 difference:
o Max: heart 114ml/min(65%) ; liver (50%)
o Min: Kidneys 14, carotid body
Resistance:
o Max: Skeletal Muscle/kg; skin (absolute)
Cardiac Output %total:
o Max: Liver 27.8
o Min: heart 4.7
O2 consumption:
o Max: liver, mm, brain
o Min: skin
6.Circulation through Regions -
Autoregulation
Definition & Intro
The ability of organs to ensure adequate perfusion in the face of changes in perfusion pressure ( P )
or changes in metabolic demand, by means of local mechanisms only.
Ohm law: Qorgan =
P
VRorgan
( VR = vascular resistance for the organ in question)
P = MAP - venous pressure

( MAP = same through out the body in supine, but venous pressure differ from organ to organ. Also, if a Starling resistor applies, a
third pressure comes into play, and P = MAP (larger of VP and 3rd pressure)
From Ohms law, one can see that, to maintain a constant perfusion (Qorgan), the organ will need to
change its vascular resistance (VR)
8L
Vascular resistance for laminar flow = r4
only way organ can change its Vasc resistance is by changing radius of supplying vessel
& this is powerful mechanism due to r4 effect
2 types of autoreg:
o pressure aka myogenic
o metabolic
in many organs combo of mechanisms exists
! usually one more predominant than other
NB in kidneys also a 3rd mechanism = Tubuloglommerular feedback (TGF) which interlinks with
pressure autoreg
Pressure Autoregulation
= ensures adequate flow in the face of changing perfusion pressure
if an MAP then vasoC to the organ to normalise flow
myogenic theory states that stretch of vessel causes it to constrict & vice versa
method not understood may be
o endothelial production of vasoconstrictor (?endothelin) in response to intraluminal pressure OR
o stretch prolonged depolarisation open probability of VOC Ca channels
organs where pressure autoreg predominant:
o total cerebral circ
o renal
o coronary metabolic is also impt but it resets pressure autoreg to operate at higher flows
Metabolic
= ensure adequate flow in face changing metabolic demands
eke metabolic hyperaemia, metabolic vasoD
locally produced metabolites as well as O2 & CO2 vasoD or supply vessels
! lactic acid, H, ADP, adenosine, K
organs where metabolic predominant:
o coronary (see above)
o skeletal mm
o Regional cerebral circ:
! Pressure autoreg determines total cerebral flow unless eg generalised seizures
Cerebral Circulation
Vessels
Inflow to brain:
o 2 carotids
o 2 vertebrals basilar
Little crossing over side to side as pressure equal both sides
are precapillary anastomoses between cerebral vessels but flow not enough with sudden occlusion
Outflow:
o Dural sinusesIJV
o Ophthalmic & pterygoid venous plexous emissary veins scalp paraverterbral veins in
spinal canal
Endothelial cells of capillary wall
o Gaps inbetween
o Few vesicles in cytoplasm little vesicular transport
! multiple other transport systems
Choroid epithelial cells on top have tight junctions
Astrocytes:
o Surround brain capillaries
o Do not cover entire capillary wall
o Gaps in end feet on basal lamina of 20nm
Cerebral Blood Flow & Regulation

Average brain weighs ~ 1400g ( 40% grey and 60% white matter),
Receives an average blood flow of 54ml/100g/min
! grey matter basal flow ~ 100ml/100g/min
critical blood flow awake = 20mls/100g/min
Av brain
o Total flow = ~750ml/min
o = ~ 15% of CO
global flow constant but see regional changes in flow in cortex
QBrain =
P__
CVR
and thus
DO2Brain = QBrain x CaO2 )
P = MAP (@level of brain) CVP or ICP (whichever is bigger)

CVR = cerebral vascular resistance
! arterioles of cerebral circ are short
arteries account for ~40-50% CVR (unusually high)
! receive rich autonomic supply
CBF = CPP/CVR
CPP = MAP (higher of ICP or CVP)
Special Tasks of Cerebral Circulation

Need for totally secure DO2Brain:
o Grey matter:
! highly metabolically active (VO2 ~7mlO2/100g/min)
! accounts for ~20% total basal VO2
! extremely sensitive to hypoxia:
seconds of ischaemia LOC
minutes irreversible damage
o primary task (of whole cardioresp system) is to ensure uninterrupted DO2Brain
Adjusting local supply to local demand:
o Mental functions are localised to well defined regions eg vision in occipital cortex
o Local neuronal activity ed local metabolic rate
Adaptations to Meet Special Tasks

Structural Adaptations
Circle of Willis
o 2 entry vessels into cranium:
! basilar
! ICA
o Form cicle of willis around optic chiasma
o ACA, MCA, PCA all arise from circle
o If blockage of 1 ICA should be redundancy from contralateral side
! true in young, less so in elderly
o Main cerebral arteries divide into pial arteries
o Pial arteries run over surface of brain
o Finer arteries arise from pial arteries and penetrate parenchyma to form short arterioles
High Capillary density:

o Grey matter contains av 3000-4000 capillaries/mm2
! ie similar ot myocardium
o High density
! large exchange area
! minimises extravascular diffusion distance
Functional Adaptations
1. high basal blood flow
2. protection of cerebral flow by reflex control of other circulations
3. cerebral autoregulation
4. Sensitivity to PaCO2 & hypoxia
5. Regional functional hyperaemia in brain
6. Nervous innervation of intra & extracerebral vessels
7. BBB
1. High Basal blood Flow
grey matter:
o receives ~ 100ml blood/100g/min
o ie x 10 the whole body average
o extracts ~ 35% of the delivered O2 (~3 3,5 mlO2/100g/min).
2. Protection of cerebral flow by reflex control of other circulations
Ohms equation on laminar flow states that blood flow to organ is dependant on balance of pressure &
resistance ie MAP & CVR
This present in brain as well as other organs
BUT brain able to safeguard its own blood supply by:
o controlling CO &
o vasc resistance of other organs
! via modulating autonomic output
brain can sacrifice other organs perfusion to protect it own
! all except heart
3. Cerebral AutoRegulation
pressure autoregulation v well developed in brain
purely local mechanism
autoreg =allows maintenance of norm cerebral blood flow if arterial pressure 50-175mmHg
function:
o in MAP cerebral vasoD maintain CBF
o in MAP cerebral vasoC limit CBP
! autonomic activity can augment length of plateau via further VC
vasodilators eg ACEIs do opposite ie shortern plateau
mechanism:
o myogenic predominantly pressure autoregulation
o metabolic (less) - mostly involved in changes in regional flow
limits: <50 and >175mmHg see sharp changes in CBP with anymore extremes of MAP
! ie greater pressure increase without incr in blood flow to head
vasoC
vasoD
4. Sensitivity to PaCO2 & Hypoxia

PaCO2 vaso D of cerebral vessels
PaCO2 vasoC
CBF changes linearly with changes in PaCo2 between 20 80mmHg
! ~ 4% change / mmHg PaCO2 change
The CBF of PaCo2 diminishes after approx. 4-6hrs due to:

o HCO3 equilibriates across BBB
o Normalisation of interstitial fluid pH
o CBF return to baseline
! after this a sudden return to normal PaCo2 CBF & ICP
Outside CBF-PCO2 response curve (<20 and >80):
o levels out at low PaCO2s due to:
! VasoC hypoxia cerebral vasoD
o Upper limit of CBF due to vessel maximal vasoD
Effect of PaCO2 on pressure autoregulation:
Hypoxia:
o causes cerebral vasoD
o only see CBF when PaO2 < 50mmHg then steep in CBF as vasoD occurs
o this mechanism dictated by OHDC:
! DO2brain only starts to when PaO2 <60mmHg (ICU point)
! ie steep drop off of O2 content from this point
The vasoD from hypercarbia and hypoxia likely mediated by NO from endothelial cells
5. Regional Functional Hyperaemia in Brain

= metabolic autoregulation
Cause for cortical metabolic hyperaemia due to:
o interstitial K from outward K currents from active neurons
o H+
o Adenosine
This system (metabolic regional autoreg) should not influence total CBF unless:
o Generalised seizure CBF
o Induced coma with drugs that CMRO2 eg thiopentone CBF
6. Nervous Innervation of Intra & Extra Cerebral Vessels
Intracerbral arteries poorly innervated
Extracerebral arteries well innervated by symp constrictor vessels
! NB brain vessels dont really participate in art baroreceptor reflex
Control of vasculature:
o Direct SympNS input:
! postganglionic sympathetic neurons:
cell bodies = sup Cx ganglion
endings vasoC
o Noradenaline
o Neuropeptide Y
! Poor max cerebral response of only ~37% vascular resistance
o Direct Parasymp NS input (vasoD) to cerebral arteries:
! Cholinergic neurons
Originate = sphenopalatine ganglia
! Postganglionic cholinergic neurons:
Endings = Acetylchline & VIP
o Hormonal control - only have few alpha adrenoceptors respond poorly to circulating NA
o Perivascular nerve fibres:
! 5-HT potent vasoC effect on cerebral arteries
! along with high K implicated in vasospasm following SAH
! 5-HT implicated in migraines
sensory fibres see abundance of perivascular sensory fibres cause pain in vascular headache ie
migraine/stroke
Role of vasoC innervation is to protect BBB against sudden rises in bp
7. Blood Brain Barrier
BBB function:
o excludes lipid insoluble substances from crossing into brain interstitium ie toxins
o conserves neuropeptides (would otherwise wash away after release
brain neuronal environment is most tightly controlled environment in body
! neurons protected from fluctuating ion & catecholamine levels in blood stream
BBB can be disrupted by:
o Acute severe HTN
o Cerebral ischaemia
o cerebral infection/meningitis
o Head injury
Formed by
o tight junctions in:
! Capillary endothelial cells
! Epithelial cells in Choroid plexus
o Basement membrane
o Astrocyte foot processes
Penetration of BBB:
o Active transporter systems to get things in:
! GLUT1 transporter in brain in 2 forms:
GLUT 1 55K
o High conc in capillaries
GLUT 1 45K
! Other transporters:
Thyroid hormones
Organic acids
Choline
Amino acids
o Several drugs & peptides cross cerebral capillaries passively
! transported back by multidrug nonspecific transporter
! ATP dependant P glycoprotein in apical membrane endothelial cells
! movement out of brain is more free than into it
o Easy to penetrate bbb:
! Lipid soluble steroid hormones
! Water
! Co2
! O2
o Difficult to penetrate:
! Lipid insoluble substances
! Urea slow penetration
! Protein bound steroid hormones
! Proteins
! Polypepides
BBB is absent in some areas =
o Circumventricular area:
! Neurohypophsysis aka post pituitary
! SCO
! Area postrema
Chemoreceptor trigger zone for vomiting based chemical changes in plasma
Angiotensin II bp
! OVLT supraoptic crest
Osmoreceptor controlling vasopressin secretion
IL1 fever
! SFO subfornical organ
Angiotensin II polydipsia
! these areas have fenestrated capillaries seen to be outside bbb
Functions of these areas:
o Neurohormonal organs secrete polypeptides into circulation
o Chemoreceptor zones sense substances from circulation which dont penetrate bbb
! Note: pineal gland & anterior pituitary are outside bbb
Development of BBB:
o BBB less developed in infants
! eg jaundiced infants with high free bilirubin bilirubin enters brain kernicterus
(basal ganglia damage)
Special Problems Facing Cerebral Circulation

Effect of Gravity
Gravity has no direct effect on CBF during orthostatsis as cerebral circulation behaves like inverted U
tube:
o Arterial limb drag
o Venous limb & CSF equivalent drag encouraging movement through U tube
! remember Starling resistor
Does have indirect effect via CVP & SV CO when moving into standing
! need quick baroreflex to prevent postural hypotension and syncope
Encasement of brain in Rigid Cranium
Monro Kelly doctrine see below
Measurement of Cerebral Circulation

Fick principle
o Nitrous oxide most common
o Xenon 133
Ketty Scmidt:
o 10% NO2 over 15-20mins
o map arterial & venous conc
o gap in middle of 2 sigmoid curves = flow
Carotid angiography
Transcranial dopplerimetry
SPECT imaging
Cerebral Spo2 monitoring
Brain Metabolism
O2 Consumption
Cerebral metabolic rate for o2 = 20% total body resting
o2 consumption
Loss of o2 LOC in 10secs
Brain stem more resistant to hypoxia creates
vegetative state with loss of higher reasoning
Most sensisitve =
o basal ganglia chronic hypoxia Parkinsonism
o thalamus
Energy for Brain

glucose:
provides 90% energy to maintain ion gradients across membranes
GLUT 1 transports it in across capillaries
Other GLUT transporters then redistribute it
Insulin not required to use glucose
Other substances can be used if lack of glucose
In normal conditions: 30% glucose converted to:
! Amino acids/proteins
! lipids
Respiratory Quotient of cerebral tissue = 0.95-0.99
o
o
o
o
o
o
Glutamate & Ammonia Removal
Glutamate [in] glutamine [out]

Glutamate [in] + ammonia glutamine
! detoxifying mechanism to remove amnonia
! opposite to reaction in kidneys
Spinal Cord Circulation

Arterial
mainly dependant on 3 longitudinal vessels:
o anterior median longitudinal spinal artery (Ant spinal artery)
! from convergence of vertebral arteries in midline
! runs length of spinal cord in ant media fissure
o pair (x2) of posterolateral trunks (posterior spinal arteries):
! from vertebral arteries
! receive contributions from post radicular arteries
! at some points along cord almost disappear making arteries look discontinuous
these vessels largest in Cx & Lx regions due to demand grey matter > white matter
! blood supply to Tx cord is poorest between T4-T9
ASA
sulcal arteries:
o arise from ASA and penetrate ant 2/3 of cord
o alternate sides at each level
! occlusion of ASA or sulcal arteries ant spinal artery syndrome
! post 2/3 as supplied by pair of posterolateral trunks:
Ant spinal artery syndrome:

o mid thoracic esp sensitive to hypoperfusion
o initial: flaccid paralysis below level due to spinal shock
o later: spastic paralysis & UMN signs due to destruction of corticospinal tracts
o diagnosis = below level of:
! loss of pain & temp = lat spinothalamic tract
! preservation of proprioception = dorsal columns
Other Contributing Arteries
other reinforcing vessels supplying some circulation:
o major segmental arteries:
! originate depending on level:
Cx vertebral arteries
Tx posterior intercostal arteries
Lx subcostal & lumbar arteries
Sx iliolumbar & sacral arteries
! feed into radicular arteries
o radicular or segmental medullary arteries of the cord
! at every level of spine in pairs
! branch & anastomose profusely at:
intervertebral foramen
within canal extradurally
! pass through intervertebral foramina & divide into post & anterior radicular arteries to
follow longitudinal vessels
! reinforce the longitudinal vessels
o Artery of AdamKiewz:
= largest feeder of lumbar part of spinal cord
= an anterior radicular atery
origin from post intercostal artery T9-T11
reinforces circulation to 2/3 of spinal cord so is impt
L side in 80% people
o vertebral & postinf cerebellar arteries impt in Cx region
Venous
not as clearly defined as arterial circulation but tend to follow their distribution
can be highly variable
generally 2 sets of vessels:
o veins of spinal cord:
! 3 ant spinal veins freely cross communicate
drained by:
o anterior & posterior radicular veins
o feed into epidural venous plexus
o venous plexus of Batson:
! large & complex venous channel
! 3 components all cross communicate:
epidural venous plexus continues through foramen magnum into dural sinuses &
skull veins
extravertebral venous plexus
veins to osseous structures of spine
! from base of skull to coccyx
! communicates directly with IVC & SVC
no valves in spinous venous network:
o high intraabdo pressure pelvic blood passes superiorly in epidural (internal) vertebral plexus
o jugular veins obstructed blood leaves via same internal vertebral plexus
as prostatic plexus is continuous with vertebral system neoplasm prostate vertebra, spinal cord,
brain, skull
Spinal Cord Perfusion Pressure

perip op risk of spinal cord ischaemia: up to 8% in some cases:
o immediate vs delayed: 37% are delayed ie 13hr 91days
o >50% resolve with Rx
SCPP = MAP (CSF + CVP)
theory is a loss of autoregulation due to surgical intervention perfusion becomes pressure dependant
risk factors:
o prev AAA
o L subclavian occlusion
o emergency procedure
o MAP <70
o renal impairement
anaesthetic aim is:
o MAP >80
o SCPP >60
o maintain DO2
anaesthetic factors:
o maintain SCPP - vasoactives
o CSF drainage:
! risk by 80%
! 50% post op deficits can be reveres by spinal drain insertion
o intraop monitoring:
! can do motor evoked potentials (MEPs)
! requires TIVA as is abolished by volatiles & NMBs
o metabolic demand:
! hypothermia systemic (33C or epidural). no clear evidence
! pharmacological strategies:
CSF opiates spinal cord ischaemia
2 agonists ischaemia clonidine/dexmedetomidine
other good options:
o anti-inflam steroids,
o antioxidant mannitol
o antiexcitatory MgSo4, thiopentone
! preconditioning needs further trials
Epidural Content
venous plexus
spinal nerves
loos areolar tissue & fat
lymph
arteries
Coronary Circulation
Average heart weight = 300g
Receives
o Basal CO: ~84ml blood/100g/min (=200-250ml/min) = 5% CO
o Max cardiac work: 300-400ml/100g/min
VO2 (consumption):
o Basal: 6-7mlO2/100g/min (20-25mlO2/min) or ~10% basal total VO2
mismatch of %CO & %VO2 = why O2 extraction must be high ~67%
! VO2 need must be met by ing coronary flow
Qcor
P
= CVR
CVR = Coronary vasc resistance
Starling Resistor
Starling resistor exists in heart in respect to P
! 3rd pressure = intraventricular pressure (IVP)
P = aortic root pressure (larger of IVP or RAP)
! simplistic equation as flows for RCA & LCA differ during
cardiac cycle
Vessels & Valves

Aortic sinuses kept away from valves by eddy currents
Orifices patent throughout cardiac cycle
RCA & LCA arise immediately above the cusps of AV (aortic root)
LCA supplies:
o LV & septum
RCA supplies mainly RV
! dominant circulation named after which one supplies AVN:
70% people R dominant
20% co-dominant
10% L dominant
Venous blood return:

o Coronary sinus RA 95% of blood
o Ant coronary vein RA
o Thesbian veins various cardiac chambers
! some drain into LV contribute to physiological shunt
! ie contributing to normal D[A-a]O2
o Others:
! Arteriosinusoidal vessels connect arterioles to chambers
! Arterioluminal vessels arteries straight into chambers
Special Tasks
Circulation must deliver O2 at high rate to keep up with demand
@rest VO2 of myocytes is x20 of skeletal mm
@exercise cardiac work rate can x5
Structural Adaptations to Meet Tasks Required

high myocardial capillary density ~3000-5000 capp/mm2 ie ~1capp/myocyte
facilitates O2 & nutrient delivery:
o endothelial area
o ed max diffusion distance
O2 transport ed by presence of myoglobin in cardiac myocytes (3.4g/L)
Functional Adaptation
1. High basal flow & high O2 extraction

2. Autoregulation
3. Coronary vasomotor nerves
1. High basal flow & high O2 extraction
Basal flow/unit weight = ~x10 of whole body average
Myocardium extracts 65-75% O2 from coronary blood
! can to ~90% in severe exercise
! whole body average 25%
Myocardial fibre has PO2 ~6mmHg
venous blood returned to RA =
o O2 content ~50-70ml/O2/L
o PO2 ~20mmHg
Energy source - % extraction from blood:
o High: fatty acids (40-70%)
o Low: Glucose (2-3%)
! = substrate preference
NO produced continuously to encourage continuous blood supply
2. Autoregulation
Both methods of autoregulation seen in coronary flow BUT metabolic is dominant process
Metabolic Auto reg:
Extra O2 required at high work rates met mostly by flow (less by extraction):
o CBF : VO2:
! Light moderate work: linear in CBF with VO2
! High work:
in flow lags
O2 extraction forced
myocardial metabolism generates vasodilator messages in quantative manner
mechanism for VD:
o interstitial hypoxia acts directly on vascular smooth mm cells via hyperpolarization
o adenosine
! created from ATP degradation
! evidence that only see release at low PO2s only in ischaemic or flow limited
myocardium
o Co2
o H+
o K+
o lactate
o prostaglandins
Pressure Auto Reg:
is reset by metabolic auto reg to operate at higher flows
this protects myocardium against under perfusion during periods of bp to around ~50mmHg
3. Coronary Vasomotor Nerves
Coronary arteries & arterioles are well innervated by SNS vasoC fibres
! tonic d/c arteriolar tone
NB if have total cardiac symp stim to all areas ie pacemaker, myocytes:
o Predicted response would see:
! HR
! contractility
! cardiac work
o Overall balance of response actually seen:
! Metabolic vasoD outweighs vasoC effect sof sympathetics
! CBF s ie metabolic autoreg overrides SNS
Also see endothelial receptors for circulating catecholamines:
o -adrenergic receptors VC
o adrenergic receptors VD
adrenaline release from adrenals (& iatrogenic NA) effect:
o reinforces coronary hyperaemia via B1 (also skeletal mm & liver)
o HR
o force of cardiac contraction
o VC of skin, renal, splachnic vessels
o Expected direct effect coronary VC
! but due to metabolite build up actually see overall coronary VD not VC
vagal fibres coronary VD
severe cold can induce reflex SNS mediated coronary vasoC in hearts with CAD (coronary art disease)
! not in norm hearts
Special Problems
1. Effect of Changes in IVP During Cardiac Cycle on RCA & LCA Flow
2. Acute Coronary Artery Obstruction
3. Gradual Obstruction
1. Effect of Changes in IVP During Cardiac Cycle on RCA & LCA Flow
pressures in heart during cardiac cycle:
o Systole:
! L ventricle = 120 mmHg
! R vent = 25
! Aorta = 120
o Diastole:
! L vent = 5mmHg
! R vent = 2
! Aorta = 80
Pressure higher in L vent during systole flow in aorta

But IVP in systole > aortic root pressure no coronary blood flow
! same as West zone 1 in lung (P > Pa >Pv and thus no flow)

o no flow in systole to coronary vessels of subendocardial portion of L vent
! why this portion most susceptible to ischaemic damage
! is some flow to superficial portions of L vent in systole
o pressure in R vent < aorta do get flow in systole
LCA receives bulk of CBF because of ed LV mm mass
P is usually measured as aortic diastolic pressure (ADP) less the larger of LVEDP or RAP
A
Blood flow to L vent is ed with aortic stenosis because L vent pressure must be much higher than
aorta to achieve outflow
Coronary flow also ed when aortic diastolic is low as effective coronary perfusion pressure
! seen in heart failure shunting blood to venous side of circ
2. Acute Coronary Artery Obstruction
Cross connections do exist between branches of coronary arteries BUT few and small
coronary arts = functional end arteries
clot to art residual flow downstream <10% acute ischaemia
MI most frequent in subendocardium as wall stress greatest here
! endocardial flow lowest at low perfusion pressures
3. Gradual Obstruction
Atheroma gradual narrowing then anastomoses have time to enlarge & maintain precarious nutrient
flow
BUT cannot supply additional flow needed for exercise/stress angina
Measurement of Coronary Flow

For absolute flow = Coronary sinus thermal dilution method
O2 Supply vs Demand of the Heart

Supply
Myocardial DO2:
DO2Cor = CaO2 x QCor
CaO2 = (Hb x1.39 x SpO2) + (PaO2 x 0.03): important = Hb, SpO2

QCor = P* / CVR : NB = aortic diastolic P, LVEDP (Starling resis), radius4,
Heart rate: rate decreased diastolic filling time (most impt in LV)
Demand
Basal requirements ( ie VO2 of ~ 6-7 mlO2/100g/min)
Heart rate: HR demand (thus, HR = double edged sword re O2 balance)
Contractility
Wall stress: (S = P.r/2w):
o IVP: Afterload (eg MAP) + Preload (LVEDP)
o radius (eg dilated heart)
o wall thickness(w) will decrease wall stress
The Balance
O2 extraction already high demand (initially) met by ing flow
Metabolic autoreg (radius) vital in ing flow
! less effective in atherosclerotic arteries
BBlockers are very good for O2 balance:
o HR
o contractility
o central SNS output
o renal renin production
clinically used indexs:

o supply = diastolic P time index (DPTI)
! = AUC for diastolic part of of an aortic + LV pressure trace
o demand = tension time index
! = AUC for the systolic part of the trace
! from these the endocardial viability ratio (EVR) can be calculated (see A-Z anaesthesia)
EVR = DPTI/TTI (ie supply/demand)
If <0.7 likelihood for ischaemia
Renal Ciculation
See renal notes
Hepatic Circulation
Liver = 2400g
Receives 57ml/100g/min or 1500ml/min = 30% CO
Divided flow:
o Hepatic art 300-500ml/min = 40-50% hepatic DO2
o Portal vein 1000-1200ml/min = 50-60% hepatic DO2
VO2 = 2mlO2/100g/min or 50mlO2/min = 20% total basal VO2
QHep art = ( MAP hep venous P ) / Hep vascular resistance = 25% total flow
QPort vein = ( Portal venous P hep venous P ) / HVR
= 75% total flow
As already high blood flow to liver: if O2 demand then oxygen extraction rather than flow
Flow Pressures
pressures:
o portal venous norm ~10mmHg
o hepatic venous norm ~ 5mmHg
o hepatic artery branches mean norm ~ 90mmHg
hepatic arterioles large adjustment pressure prior to blood entering sinusoids
! drugs which alter presinusoidal pressure have little effect on sinusoidal pressure
if systemic venous pressure:
o passive dilation of portal veins flow into liver
o eg chronic systemic pressure in heart failure hepatic venous congestion
! ie big difference in effect on liver arterial vs venous pressure changes
if systemic arterial bp NA discharge:
o intrahepatic portal veins constrict portal pressure blood flow into liver
blood bypasses and stays in systemic circulation
o hepatic arterioles constriction blood stays in systemic circ
o mesenteric arterioles constriction portal inflow
inverse relationship between hepatic artery & portal venous blood pressure
reserve sinusoids are recruited during times of ingestion
prevents portal pressures ing linearly with portal flow which would fluid loss into
ascites eg in hard liver states cirrhosis
vasoconstriction:
o intrahepatic portal vein can vasoC in response to NA vasoC nerve fibres
o hepatic artery via fibres from hepatic symp plexus
large gaps between sinusoidal endothelial cells large permeability (reflection coefficient ~0)
lymph drainage high in protein
Hepatic Artery vs Portal Vein

Autoregulation:
o Intrinsic:
! Portal vein :
flow related linearly to pressure
if flow through hepatic artery portal vein can not compensate
(can only vasoC via extrinsic mechanism)
! Hepatic artery has some degree of metabolic autoreg can adjust 50% of flow via this
mechanism
Hepatic buffer response:
o if portal vein flow hepatic art flow and vice versa
o = hepatic arterial buffer response
o mediated by adenosine (vasoD) not being washed away by low portal flow
vasoD of hepatic arterioles
o if portal vein pressure hep artery flow - ?due to myogenic mechanism
! eg in heart failure
o Extrinsic:
! SNS activity:
portal vein flow via splachnic venoC
hepatic art flow
liver venoC emptying of hepatic blood reservoir into systemic circ
o ! ~ 350-500ml blood
! acute haemorrhage:
portal venous blood > systemic arterial flow
O2 supply to liver maintained by extraction
! other causes hepatic blood flow:
feeding - s intestinal blood flow hepatic blood flow
hypercapnia
! other causes hepatic blood flow:
vasopressin vasoC hepatic vasculature
heavy exercise: splachnic vasoC
+ve pressure ventilation via CO
hypocapnia: flow by 30% via resistance in portal venous system
hypoxia initially arterial flow but return to norm in 20mins (no effect on portal)
if blood supply change to liver O2 consumption met by ing O2 extraction
delivery of O2 to liver:
o 40-50% hepatic artery = even though 1/3 of flow
o 50-60% portal vein
Effect of Anaesthesia on Hepatic Blood Flow
categorise:
o drug effects
o effects of ventilation & surgery
Drugs
generally all drugs which CO liver blood flow
spinal & epidural
o depends on level of block eg T4 = 20% flow
o portal & mean art pressure total hep blood flow
inhalational agents generally total hep blood flow:
o halothane = greatest total hep flow:
! due to ed hep arterial resistance despite ed portal venous flow
! ie hepatic arterial buffer response
o enflurane = similar effects to halothane but less severe
o isoflurane/des/sevo = minimal or no change
! hep arterial flow unchanged or ed if ed portal flow
! ie hepatic arterial buffer working better
IV agents (thio, etomidate, propofol) = dose dependant hepatic blood flow caused by:
o CO
o hepatic arterial buffer mechanism
blockers (propranolol) flow
induced hypotension eg SNP inversion in contribution of hep artery & portal venous supplies
H2 antagonists
Effects of Surgery
Upper abdo surgery = flow 60%
Ventilation:
o IPPV: portal flow due to splachnic resistance
o PEEP: further flow due to hepatic venous pressure (via CVP)
Summary
All anaesthesia hepatic blood flow
BUT O2 requirements also so rarely a problem
Measurement
via Fick principle

use indocyanine green as indicator
dye is removed from circ only in liver
totally excreted in bile with no enterohepatic recirculation
level in body measured by spectrophotometry
method:
o give dye by constant infusion until steady state ie infusion = hep elim rate
o periph artery is measured (as indirect marker of hep artery)
o catheter sampling placed in hepatic vein for sampling
rate of uptake of substance = (amount entering tissue) (time)
Or: Vx = Q.ca Q.cv
= Q(ca cv )
(amount leaving the tissue)

(time)
thus: Q = Vx / (ca cv )
Remember: Indocyanine green is used in the indicator dilution (washout) technique to measure cardiac output.
Cutaneous Circulation
av weight = 2.5kg
flow ~ 15ml/100g/min (thermoneutral) = ~300ml or 6% CO
min flow = 1ml/100g/min
max flow = 150-200ml/100g/min
VO2 ~ 0.3mlO2/100g/min = 12mlO2/min or 4.3% basal VO2
Special Tasks
Thermoregulation
Core temp kept +/- 1deg C of 37
Done by balancing internal heat loss production with external heat loss
Heat loss occurs by 4 methods:
o Radiation:
! Most significant in theatre patients
! Rate loss proportional to diff between ambient temp vs skin temp
! Skin temp dependant on rate of blood flow to skin
o Conduction & convection:
! Warm skin heats adjacent air, convection moves air away
! Rate of heat loss proportional to skin ambient temp differential
o Evaporation:
! 2.4KJ heat energy consumed/gram water evaporated
! = latent heat of evaporation
! water & heat delivered to skin by blood flow
! blood flow vital for all mechanisms of loss
skin = poikilothermic ie over short periods can tolerate temp extremes 0-45degs
Response to trauma/Defence
vasoD in response to trauma healing
Structural Adaptation
Arteriovenous Anastomosis in the Extremities (AVAs)

aka sacral areas
= exposed areas with high SA/volume ratio eg finger, toe pal, lips, nose, ears
exists direct connections between dermal arterioles & venules
AVAs =
o coiled muscular walled vessels av diameter 35um
o no basal tone
o activity controlled exclusively by SNS (constrictor fibres)
! have basal tonic d/c
o SNS controlled by temp regulation centre in hypothalamus
o core temp SNS output dilation AVAs low resistance shunt skin flow
o converse in cold
SNS control:
o Dominant & regulated by core temp receptors
Direct sensitivity of vessel tone to local temp change:
o Hand immersed in <10deg water:
! Initial cold induced constriction
! ing painful sensation
! 5-10min: vasoD reddening of skin & relief of pain
! occurs in AVA rich areas thought due to paralysis of NA transmission
prevents skin damage in prolonged exposure to cold ie red nose
dependant vasoC by local mechanisms:
o eg vasomotor reflexs
o 1hand in cold water modest vasoC seen in other hand
o due to SNS mediated spinal reflex initiated by temp receptors in immersed hand
role & reg of arterial MAP & CVP
o eg reflex vasoC & venoC in response to shock
o this 2ndary to neural reflexes & circulatory hormones
triple response to cutaneous trauma:
o creates hyperaemia, cap permeability & delivery defensive elements to injured tissue
o see below
Special Problems
compression with weight bearing/bed sores:

o ischaemic damage usually prevented by
! high tolerance of skin to hypoxia
! reactive hyperaemia on removal stress
! behavioural responses eg restlessness
hot weather problems:
o local swelling
o venoD & pooling blood post hypotension
Measurement of Skin Circulation

digital plethysmograph
Ketys isotope clearance method
Laser-Doppler flow probe
Examples of Skin Reactions

White Reaction
= pointed object drawn lightly over skin pale stroke line in ~15secs
due to mechanical stimulus contraction precapillary spincter blood drain out capillarys
Triple Response
more firm stroke of pointed object:
o red reaction
! in ~ 10 sec
! capillary dilation in response to pressure
o wheal:
! = swelling & mottling
! permeability of capillaries & venules
! mediated by substance P
o flare:
! = redness spreading from injury
! arteriolar dilation
! due to axon reflex:
antidromic conduction
! impulse from sensory nerve doesnt go to spinal cord but are relayed back down
other branch of sensory nerves to arteriole
reaction persists after sympathectomy
Reactive Hyperaemia
blood supply to limb occluded arteriole below occlusion dilate 2nd to local hypoxia
circ restablished blood into dilated vessels
Generalized Responses
cold blue skin =
o arteriole VC;
o capillaries VD
! Warm red skin = both dilated

Norad & adrenaline VC of cutaneous vessels
VD caused by:
o constrictor tone 2nd to Norad & adrenaline
o local VD metabolites
! there are no VD nerve fibers to skin
examples of skin reaction:
o painful event: Norad d/c generalised skin VC & triple response
o exercise:
! norad BUT body temp rise overcomes VC VD
o pyrexial: hypothalamic temp overcomes other reflex activity VD
! why if pyrexial shock is more profound
o hypothermic:
! initially VC
! later in severe temp superficial VD
Muscle Circulation
weight ~ 50kg
flow ~2-3ml/100g/min (resting), 1000ml/min = 20% CO
VO2 ~ 0.2mlO2/100g/min = 50mlO2/min = ~20% total basal VO2
Special tasks
Delivery O2 & nutrients & removal of waste products in proportion to requirement

Contribution to homeostasis of MAP:
o Skel mm
! contains ~40% total body water
! large vasc beds which affects SVR as required
participation in vascular reflexs:
o mm arterioles richly innervated by SNS (cholinergic fibres)
o art baroreflex controls vasoC nerve activity
dominance of metabolic autoregulation during exercise:
o during hard exercise see blood flow to 80-90% of CO
o in % CO almost entirely due to fall in local vasc resistance by metabolic vasoD
! rather than due to modest MAP
o flow linearly with local metabolic rate
o timing:
! 1st few mins:
interstital K vasoD
interstital osmolarity further vasoD
! later:
inorganic phosphate released from contracting mm vasoD
hypoxia augments above factors
diffusion distances by capillary recruitment (resting mm 1/3 capillaries perfused)
o maintainence of ed flow mechanism is unclear adenosine implicated
variable oxygen extraction & O2 debt
o resting mm 25-30% extraction
o exercise 80-90% extraction
o in severe exercise intracellular PO2 falls so low anaerobic glycolysis predominates lactic
acid
o lactate & K stim local nociceptors pain
o amount of lactate = index of deficit O2 supply
o O2 debt can reach several litres of lactate
o Post exercise:
! Post exercise hypraemia
! Gradually washes out accumulated lactate & other VasoD substances
! Small amount lactate metab locally the rest moved away by blood stream to:
liver (majority) resynthesis into glycogen
heart primary substrate for energy
skeletal mm pump:
o massaging effect of isotonic contraction VR aided by venous valves
vasodilator response of skeletal mm arterioles to adrenaline:
o in physiological doses circulating adrenaline vasoD via B2 receptors in:
! skeletal mm
! Gs linked cAMP
! heart
! liver
Special Problems
mechanical interference during contraction:
o forceful contraction can compress vessels flow esp isometric
! not major issue in isotonic contraction
o mm myoglobin O2 store only sufficient for 5-10secs
o fibres rapidly hypoxic lactate pain & fatigue
fluid translocation across capillaries 10-15% plasma volume
Measurement
venous occlusion plethysmography

Doppler velocity meter
Ketys isotope clearance method
Summary Relationship Between CO & Regional

Circulations
Tissues control the CO to themselves as a consequence of autoregulation:
o Pressure
o Metabolic
Sum of all local organ & tissue flows = CO
Heart is a demand pump ie delivers required output as set by the tissues
Autonomic n.s (mainly SNS) maintains a constant MAP in order to allow each tissue to adjust its
blood flow indep of other tissues:
o Doen by adjusting local arteriolar resistance
SNS activity if very high might adversely flow to some tissues but important tissues (brain, heart,
kidney) benefit due to
o ed level of nervous control
o & better developed autoregulation
both autoreg & SNS achieve effects by changing arteriolar resistance
(! also effects CO by means of inotropy, chronotrophy, varied afterload)
SNS changes SVR: MAP = SVR x CO)
Autoreg changes local resistance: Q = MAP/resistance
stable MAP vital:
o organ manipulates local resistance without effecting systemic MAP

ANCZA Heart Physiology Combined Notes 1-6

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ANCZA Heart Physiology Combined Notes 1-6

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By Adam Hollingworth

Origin & Spread of Excitation

Cardiac Muscle APs & Pacemaker APs

seen only in SA, AV nodes

ionic basis same for AVN & SAN

Spread of Cardiac Excitation

! allowing atria to finish filling ventricles before they contract

Normal sinus rhythm originated in SA node

Delayed After Polarisations

Caused by inward current assoc with abnormally raised intracellular Ca

Ectopic Foci of Excitation

Common cause of paroxysmal tachyarrhythmias = defect in conduction permits circus movement

ectopic vent focus extrasystole:

long QT ventricular repolarisation is irreg incidence of arrhythmia

Myocardial Excitability vs Irritability

12 lead ECG 3 unipolar leads are recorded ie aVR, aVL, aVF

Place electrodes closer to heart around thorax

His Bundle Electrogram

ECG Monitoring Systems in Anaesthetics

ECG observed alone 1 bipolar lead between 2 electrodes

Modified 3 Lead System

Surface Recordings Compared to Actual APs

Diseases Effecting ECGs

hours few days

Late Established Pattern

Very Late Pattern

Post MI Vent Arrhythmias

Electrolyte Effects on ECG

Atrial & vent pressure both low

Atrial Systole (late Diastole)

@ start AV valves close isovolumetric contraction:

Myocardium epicardium pericardium

R atrial systole then L atrial systole

Length of Systole & Diastole

Duration of systole is more fixed than diastole

Blood flow speeds up through narrowing eg:

Factors Effecting EDV

Relation of Tension to Length in Myocardium (Starlings Law)

Nb force of contraction or initial fibre length difficult to measure

For thick walled sphere or tube:

thus wall stress ed by:

Positive Inotropic Factors

Functional Factors Effecting CO Overall

Ventricular Function Curves

EDVP line as shown

Effect of Isolated Preload on LV PV Loop

Effect of Isolated Afterload

Isovolumetric contraction (upstroke):

Vascular Function Curves

Effect of change in SVR (ie afterload)

Coupling Between Heart & Vasculature

Curve shows how disturbances in equilibrium are dealt with:

Summary effect = SNS stim greater CO at same CVP

Effect of Transfusion on Coupling

Coordinated Effect of Max Symp Activity (in Vivo)

Effect of Heart Failure

Athletes, Heart Transplant & Sympathetic

3.Dynamics of Blood Flow

3.Dynamics of Blood Flow -

Vascular Smooth Muscle

vital in regulating vessel diameter

Arteries & Arterioles

Arterioles metarterioles capillaries

seen in fingers, palms, ear lobes