Physiology
Cardiovascular System
PreMMed Course 2013
East Coast Basic Science Course
• What events occur in the heart each time it beats?
• How much blood does the heart pump out?
• What factors affect the amount of blood the heart
pumps out?
• How is blood pressure related to blood flow from the
heart?
• What are the normal cardiovascular response to
hypovolaemia?
• How do anaesthetics affect the cardiovascular system?
Cardiovascular System Function
• Functional components of the cardiovascular system:
– Heart
– Blood Vessels
– Blood
• General functions these provide
– Transportation
• Everything transported by the blood
– Regulation
• Of the cardiovascular system
– Intrinsic & extrinsic
– Protection
• Against blood loss
– Production/Synthesis
Cardiovascular System Function
• To create the “pump” we have to examine the
Functional Anatomy
– Cardiac muscle
– Chambers
– Valves
– Intrinsic Conduction System
Functional Anatomy of the Heart
Cardiac Muscle
• Characteristics
– Striated
– Short branched cells
– Uninucleate
– Intercalated discs
– T-tubules larger and
over z-discs
Cardiac Ultrastructure
Cardiac Myocyte
Structural Unit:Sarcomere
Functional Anatomy of the Heart
Chambers
• 4 chambers
– 2 Atria
– 2 Ventricles
• 2 systems
– Pulmonary
– Systemic
Functional Anatomy of the Heart
Valves
• Function is to prevent backflow
– Atrioventricular Valves
• Prevent backflow to the atria
• Prolapse is prevented by the chordae
tendinae
– Tensioned by the papillary muscles
– Semilunar Valves
• Prevent backflow into ventricles
Functional Anatomy of the Heart
Intrinsic Conduction System
• Consists of
“pacemaker” cells
and conduction
pathways
– Coordinate the
contraction of the
atria and ventricles
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Characteristics of
Pacemaker Cells
– Smaller than
contractile cells
– Don’t contain many
myofibrils
– No organized
sarcomere structure
• do not contribute to
the contractile force of
the heart
conduction myofibers
normal contractile
myocardial cell
SA node cell
AV node cells
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Characteristics of Pacemaker Cells
– Unstable membrane potential
• “bottoms out” at -60mV
• “drifts upward” to -40mV, forming a pacemaker potential
– Myogenic
• The upward “drift” allows the membrane to reach threshold
potential (-40mV) by itself
• This is due to
1. Slow leakage of K+ out & faster leakage Na+ in
» Causes slow depolarization
» Occurs through If channels (f=funny) that open at negative
membrane potentials and start closing as membrane approaches
threshold potential
2. Ca2+ channels opening as membrane approaches threshold
» At threshold additional Ca2+ ion channels open causing more rapid
depolarization
» These deactivate shortly after and
3. Slow K+ channels open as membrane depolarizes causing an
efflux of K+ and a repolarization of membrane
Pacemaker Action Potential
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Characteristics of Pacemaker Cells
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Altering Activity of Pacemaker Cells
– Sympathetic activity
• NE and E increase If channel activity
– Binds to β1 adrenergic receptors which activate cAMP and
increase If channel open time
– Causes more rapid pacemaker potential and faster rate of action
potentials
Sympathetic Activity Summary:
increased chronotropic effects
heart rate
increased dromotropic effects
conduction of APs
increased inotropic effects
contractility
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Altering Activity of Pacemaker Cells
– Parasympathetic activity
• ACh binds to muscarinic receptors
– Increases K+ permeability and decreases Ca2+ permeability =
hyperpolarizing the membrane
» Longer time to threshold = slower rate of action potentials
Parasympathetic Activity
Summary:
decreased chronotropic effects
heart rate
decreased dromotropic effects
 conduction of APs
decreased inotropic effects
 contractility
Myocardial Physiology
Contractile Cells
• Special aspects
– Intercalated discs
• Highly convoluted and interdigitated
junctions
– Joint adjacent cells with
» Desmosomes & fascia adherens
– Allow for synticial activity
» With gap junctions
– More mitochondria than skeletal muscle
– Less sarcoplasmic reticulum
• Ca2+ also influxes from ECF reducing storage
need
– Larger t-tubules
• Internally branching
– Myocardial contractions are graded!
Myocardial Physiology
Contractile Cells
• Special aspects
– The action potential of a contractile cell
• Ca2+ plays a major role again
• Action potential is longer in duration than a “normal” action potential
due to Ca2+ entry
• Phases
4 – resting membrane potential @ -90mV
0 – depolarization
» Due to gap junctions or conduction fiber action
» Voltage gated Na+ channels open… close at 20mV
1 – temporary repolarization
» Open K+ channels allow some K+ to leave the cell
2 – plateau phase
» Voltage gated Ca2+ channels are fully open (started during initial
depolarization)
3 – repolarization
» Ca2+ channels close and K+ permeability increases as slower activated
K+ channels open, causing a quick repolarization
Cardiac Myocyte Action Potential
Phase 0 – Rapid Depolarisation
Phase 1 – Spike
Phase 2 – Plateau
Phase 3 – Repolarisation
Phase 4 – Diastolic potential
Myocardial Physiology
Contractile Cells
• Skeletal Action Potential vs Contractile
Myocardial Action Potential
Myocardial Physiology
Contractile Cells
• Plateau phase prevents summation due to
the elongated refractory period
• No summation capacity = no tetanus
– Which would be fatal
Summary of Action Potentials
Skeletal Muscle vs Cardiac Muscle
Excitation Contraction Coupling
Pressure in Cardiac Chambers
Cardiac Cycle
• One complete sequence that occur during the
contraction (systole) and relaxation (diastole)
of the ventricular muscle
• This activity is initiated by cardiac action
potential
Cardiac Cycle
Coordinating the activity
• Electrical
Conduction
Pathway
Cardiac Cycle
Coordinating the activity
• The electrical system gives rise to electrical
changes (depolarization/repolarization) that is
transmitted through isotonic body fluids and
is recordable
– The ECG!
• A recording of electrical activity
• Can be mapped to the cardiac cycle
Conduction speeds
Tissue
Conduction rate (m/s)
SA node
.05
Atrial pathways
1
AV node
.05
Bundle of His
1
Purkinje
4
Ventricular muscle
1
• The sum of these action potential is recorded
as the ECG
P wave – atrial depolarisation
PR interval – spread of excitation
through the atria, AV node and bundle
of His
QRS complex – spread of excitation
through the ventricles
T wave – ventricular repolarisation
Cardiac Cycle
Phases
Atrial Contraction
(A-V Valves Open, Semilunar Valves Closed)
• The first phase - initiated by the p wave of ECG - electrical
depolarization of the atria.
• Atrial depolarization then causes contraction of the atrial
musculature. As the atria contract, the pressure within the atrial
chambers increases, which forces more blood flow across the open
A-V valves, leading to a rapid flow of blood into the ventricles.
• Blood does not flow back into the vena cava because of inertial
effects of the venous return and because the wave of contraction
through the atria moves toward the AV valve thereby having a
"milking effect."
• Atrial contraction produce a small increase in venous pressure that
can be noted as the "a-wave" of the left atrial pressure. Just
following the peak of the a wave is the x-descent.
• After atrial contraction is complete, the atrial pressure begins to fall
causing a pressure gradient reversal across the AV valves. This
causes the valves to float upward (pre-position) before closure. At
this time, the ventricular volumes are maximal - end-diastolic
volume (EDV).
• The left ventricular EDV (LVEDV) ~ 120 ml, represents the
ventricular preload and is associated with end-diastolic pressures of
8-12 mmHg and 3-6 mmHg in the left and right ventricles,
respectively.
• A heart sound is sometimes noted during atrial contraction (fourth
heart sound, S4). This sound is caused by vibration of the
ventricular wall during atrial contraction.
Isovolumetric Contraction
(All Valves closed)
• This phase of the cardiac cycle begins with the QRS complex of the
ECG - ventricular depolarization.
• This triggers excitation-contraction coupling, myocyte contraction
and a rapid increase in intraventricular pressure. Early in this phase,
the rate of pressure development becomes maximal - maximal
dP/dt.
• The AV valves close as intraventricular pressure > atrial
pressure. Ventricular contraction also triggers contraction of the
papillary muscles with their attached chordae tendineae that prevent
the AV valve leaflets from bulging back into the atria and becoming
incompetent . Closure of the AV valves results in the first heart
sound (S1) - normally split (~0.04 sec) because MV closure
precedes TV
• During the time between the closure of the AV valves and the
opening of the aortic and pulmonic valves, ventricular pressure rises
rapidly without a change in ventricular volume - no ejection occurs.
• Ventricular volume does not change because all valves are closed
during this phase. Contraction - "isovolumic" or "isovolumetric."
• The "c-wave" noted in the LAP may be due to bulging of mitral valve
leaflets back into left atrium. Just after the peak of the c wave is the
x'-descent.
Rapid Ejection
(Aortic and Pulmonic Valves Open; AV Valves Remain Closed)
• Initial and rapid ejection of blood into the aorta and pulmonary
arteries from the left and right ventricles, respectively.
• Ejection begins when the intraventricular pressures > the pressures
within the aorta and pulmonary artery, which causes the aortic and
pulmonic valves to open.
• Ventricular pressure normally > outflow tract pressure by a few
mmHg. This pressure gradient across the valve is ordinarily low
because of the relatively large valve opening (low resistance).
Maximal outflow velocity is reached early in the ejection phase, and
maximal (systolic) aortic and pulmonary artery pressures are
achieved.
• Normally no heart sounds noted during ejection because
the opening of healthy valves is silent. The presence of
sounds during ejection indicate valve disease or
intracardiac shunts.
• Left atrial pressure initially decreases as the atrial base
is pulled downward, expanding the atrial
chamber. Blood continues to flow into the atria from
their respective venous inflow tracts and the atrial
pressures begin to rise, and continue to rise until the AV
valves open at the end of phase 5.
Reduced Ejection
Aortic and Pulmonic Valves Open; AV Valves Remain Closed
• Approximately 200 msec after the QRS and the beginning of
ventricular contraction, ventricular repolarization occurs (T-wave of
the ECG).
• Repolarization leads to a decline in ventricular active tension and
therefore the rate of ejection falls.
• Ventricular pressure falls slightly below outflow tract pressure;
however, outward flow still occurs due to kinetic (inertia) energy of
the blood.
• Left atrial and right atrial pressures gradually rise due to continued
venous return from the lungs and from the systemic circulation,
respectively
Isovolumetric Relaxation
All valves closed
• When the intraventricular pressures fall sufficiently at the end of
phase 4, the aortic and pulmonic valves abruptly close (aortic
precedes pulmonic) causing the second heart sound (S2) and the
beginning of isovolumetric relaxation.
• Valve closure is associated with a small backflow of blood into the
ventricles and a characteristic notch (incisura or dicrotic notch) in
the aortic and pulmonary artery pressure tracings.
• After valve closure, the aortic and pulmonary artery pressures rise
slightly (dicrotic wave) following by a slow decline in pressure.
• The rate of pressure decline in the ventricles is determined by the
rate of relaxation of the muscle fibers, which is termed lusitropy.
This relaxation is regulated largely by the sarcoplasmic reticulum
that are responsible for rapidly re-sequestering calcium following
contraction.
• Although ventricular pressures decrease during this phase, volumes
remain constant because all valves are closed. The volume of blood
that remains in a ventricle is called the end-systolic volume ~ 50
ml in the left ventricle. The difference between the end-diastolic
volume and the end-systolic volume is ~70 ml and represents the
stroke volume.
• Left atrial pressure (LAP) continues to rise because of venous return
from the lungs. The peak LAP at the end of this phase is termed the
v-wave.
Rapid Filling
A-V Valves Open
• As the ventricles continue to relax, the intraventricular pressures will
at some point fall below their respective atrial pressures. When this
occurs, the AV valves rapidly open and ventricular filling begins.
• Despite the inflow of blood from the atria, intraventricular pressure
continues to briefly fall because the ventricles are still undergoing
relaxation. Once the ventricles are completely relaxed, their
pressures will slowly rise as they fill with blood from the atria.
• The opening of the mitral valve causes a rapid fall in LAP. The peak
of the LAP just before the valve opens is the "v-wave." This is
followed by the y-descent of the LAP. A similar wave and descent
are found in the right atrium and in the jugular vein.
Reduced Filling
A-V Valves open
• As the ventricles continue to fill with blood and expand,
they become less compliant and the intraventricular
pressures rise. This reduces the pressure gradient
across the AV valves so that the rate of filling falls.
• In normal, resting hearts, the ventricle is about 90% filled
by the end of this phase. In other words, about 90% of
ventricular filling occurs before atrial contraction.
• Aortic pressure and pulmonary arterial pressures
continue to fall during this period.
Cardiac Cycle
LV Pressure-Volume Relationship
Pressure Volume Loop
Cardiac Output
• Volume of blood ejected by each ventricle
per minute
• CO = Stroke Volume, SV X Heart Rate
= l/min
• Cardiac Index = CO/body surface area
= l/min/m2
• Factors Affecting Stroke Volume
– Degree of filling of ventricle, Preload
– Contractility of myocardium
– Resistance against which the ventricle has to
work, Afterload
Preload
• The load on the myocardial muscle just
prior to the onset of contraction.
• The more a muscle fibre is stretched
before being stimulated to contract, the
greater its force of contraction.
• Limited by internal molecular structure of
muscle, that above a critical (optimal) point
further lengthening reduces force of
contraction.
Effect of Preload on PV loop
Myocardial Contractility
• (Intrinsic) ability of the cardiac muscle
fibres to contract.
• Independent of the degree of preload and
afterload.
• Referred as degree of inotropy
• +ve inotropic
– Sympathetic nervous system –
catecholamines
• -ve inotropic
– Acidosis
– Hypoxia
– Hypocalcaemia
– Drugs – anaesthetics, antiarrhythmic
Effect of Inotropy on PV loop
Afterload
• The impedence to the ejection of blood from the
heart into the arterial circulation.
• At the end of diastole, venticular muscle starts to
contract.
• Need to overcome forces that preventing it;
– Tension in ventricular wall
– Resistance to ejection of blood from ventricle
• Approximated as
– L vent afterload – resistance by systemic circulation –
Systemic Vascular Resistance (SVR)
– R vent afterload – resistance by pulmonary circulation –
Pulmonary Vascular Resistance (PVR)
Effect of Afterload on PV loop
Law Of Laplace
T = P x r/wt
Tension = Pressure x Radius / wall thickness
How does Laplace Work?
Heart Rate
• Heart has an intrinsic pacemaker, the
sinoatrial node. ~ discharged around 100
beats/min
• Control by autonomic nervous system
• Sympathetic stimulation – increase HR +ve chronotropic
• Parasympathetic stimulation (Vagus) –
decrease HR - -ve chronotropic
CO tends to fall when heart rate surpasses 150/min due to
inadequate filling time. Too low heart rate, CO also tends to drop due
to insufficient heart rate
Location
Effects
Alpha-1
Blood vessels
Vasoconstriction
Alpha-2
Blood vessels
Vasoconstriction
Beta-1
Heart
Increase heart rate
Increase force of
contraction
Beta-2
Blood vessels
Lungs
Vasodilatation
Bronchodilatation
Receptor type
Cardiac Reflexes
•
•
•
•
•
•
•
Baroreceptor reflex
Chemoreceptor reflex
Bainbridge reflex
Bezold jarish reflex
Valsalva maneuver
Cushings reflex
Occulocardiac reflex
Baroreceptor Reflex
• Stretch receptors in
walls of heart and
blood vessels
• Responsible for
maintenance of
blood pressure
Baroreceptor Reflex
↑ BP

↑ BR in carotid sinus & aortic arch

Sinus nerve & Aortic nerve

IX & X nerve

N. solitarius

↑ vagal tone

↓ HR
Chemoreceptor Reflex
↓pO2 ↑ pCO2 & ↓pH

↑ CR in carotid body & aortic arch

Sinus nerve & Aortic nerve

IX & X nerve

↑ Respiratory centre

↑ ventilatory drive
Bainbridge Reflex
Venous engorgement of atria & great veins

Stimulation of stretch receptors

X nerve

CVS center medulla

↓ Vagal tone

↑ HR
Bezold Jarish Reflex
Ischemia

Receptors in LV

X nerve

Reflex bradycardia, Hypotension & coronary
artery dilation
Valsalva Maneuver
• Forced expiration against closed glottis
• Increase in intrathoracic pressure
↑ Intrathoracic pressure → ↑CVP → ↓ V.R
→ ↓ CO &BP → sensed by BR → ↑ HR &
contractility
• When glottis opens
↑ VR → ↑ contractility → ↑ BP →sensed
by BR → ↓ HR & BP
Initial Pressure Rise
On application of
expiratory force,
pressure rises inside
the chest forcing
blood out of the
pulmonary circulation
into the L atrium. This
causes a mild rise in
SV.
Reduced VR & Compensation
Return of systemic blood to
the heart is impeded by the
pressure inside the chest.
The output of the heart is
reduced and SV falls. The fall
in SV reflexively causes
blood vessels to constrict
with some rise in pressure.
This compensation can be
quite marked with pressure
returning to near or even
above normal, but the cardiac
output and blood flow to the
body remains low. During this
time the PR increases.
Pressure Release
Return of CO
The pressure on the chest
is released, allowing the
pulmonary vessels and the
aorta to re-expand causing
a further initial slight fall in
SV due to decreased L
ventricular return and
increased aortic volume,
respectively. Venous blood
can once more enter the
chest and the heart, CO
begins to increase.
Blood return to the
heart is enhanced by
the effect of entry of
blood which had been
dammed back,
causing a rapid
increase in CO. The
SV usually rises
above normal before
returning to a normal
level. With return of
BP, the PR returns
towards normal.
• Clinical Uses of Valsalva Manoeuvre;
– Reversion of supraventricular tachycardia
– Testing autonomic function
– Aid in assessment of some heart murmurs
Cushings Reflex
↑ Intracranial pressure

Cerebral ischemia

↑ VMC

↑SNS - ↑BP

↑BR

↑CIC

↑Vagal tone

reflex bradycardia ↓ HR
Occulocardiac Reflex
Pressure on eye

long & short ciliary nvs

ciliary ganglion

gasserion ganglia

↑ PNS → BRADYCARDIA
Systemic Circulation
Physical laws governing blood flow and blood pressure
• Flow of blood through out
body = pressure gradient
within vessels X resistance
to flow
- Pressure gradient: aortic
pressure – central venous
pressure
- Resistance:
-- vessel radius
-- vessel length
-- blood viscosity
Factors promoting total peripheral resistance (TPR)
• Total peripheral resistance =
TPR
-- combined resistance of all
vessels
-- vasodilation  resistance
decreases
-- vasoconstriction 
resistance increases
Vasculature
Arteries and blood pressure
• Pressure reservoir
• Arterial walls are able to
expand and recoil because
of the pressure of elastic
fibers in the arterial wall
• Systolic pressure: maximum
pressure occurring during
systole
• Diastolic pressure: pressure
during diastole
Capillaries
• Allow exchange of gases, nutrients
and wastes between blood and
tissues
• Overall large surface area and low
blood flow
• Two main types:
- continuous capillaries:
narrow space between cells 
permeable to small or lipid soluble
molecules
- fenestrated capillaries: large
pores between cells large
molecules can pass
Movement of materials across capillary walls
• Small molecules and lipid
soluble molecules move by
diffusion through the cell
membrane
• Larger molecules, charged
molecules must pass
through membrane
channels, exocytosis or in
between 2 cells
• Water movement is
controlled by the capillary
hydrostatic and osmotic
pressures
Forces controlling water movement
• Arterial side of the capillary:
– High capillary hydrostatic
pressure (BHP), lower capillary
osmotic pressure (BOP, due to
proteins and other molecules in
the blood)  Net filtration
pressure pushes fluid from the
blood toward the tissue (but the
proteins remain in the capillary
• Venous side of the capillary:
- Lower hydrostatic pressure (due to
resistance) and higher capillary
osmotic pressure  Net filtration
pressure moves fluid back toward the
capillary
• Interstitial fluid hydrostatic (IFHP)
and osmotic pressures (IFOP)
remain overall identical
Starling’s Hypothesis
•
A quote from Starling (1896)
"... there must be a balance between the hydrostatic pressure of the blood in the capillaries
and the osmotic attraction of the blood for the surrounding fluids. "
" ... and whereas capillary pressure determines transudation, the osmotic pressure of the
proteids of the serum determines absorption.“
Starling, 1896
•
•
Starling’s hypothesis - the fluid movement due to filtration across the wall of a
capillary is dependent on the balance between the hydrostatic pressure
gradient and the oncotic pressure gradient across the capillary.
The four Starling’s forces are:
–
–
–
–
•
•
hydrostatic pressure in the capillary (Pc)
hydrostatic pressure in the interstitium (Pi)
oncotic pressure in the capillary (∏ c )
oncotic pressure in the interstitium (∏ i )
The balance of these forces allows calculation of the net driving pressure for
filtration.
Net Driving Pressure = [ ( Pc - Pi ) - ( ∏c - ∏i ) ]
CAPILLARY FILTRATION
HYDROSTATIC
FORCES
OSMOTIC FORCES
ONCOTIC PRESSURE
Arterial Pressure
Venous Pressure
Pre-post Capillary Res.
Interstitial Fluid Pressure
BALANCE
STARLING’S HYPOTHESIS
Qf = k (Pc + i) - (Pi + p)
Albumin
Veins
•
Veins are blood volume reservoir
•
Due to thinness of vessel wall  less resistance to stretch = more compliance
Normal distribution of blood volume
• Heart
• Pulmonary circulation
• Systemic circulation
Arteries
Capillaries
Veins
7%
9%
15%
5%
64%
Factors influencing venous return
• 1- Skeletal muscle pump
and valves

• 2- Respiratory pump
• 3- Blood volume
• 4- Venomotor tone
Role of The Parts of Circulation
Aorta & Large Elastic Arteries Auxillary pump to obtain continuous (though
pulsatile) flow throughout the cardiac cycle
Muscular Arteries
Distribute oxygenated blood to the tissues
Arterioles
Resistance vessels – determined the systemic
vascular resistance & the distribution of the CO
Capillaries
Exchange vessels – gas, nutrients and waste
Veins
Capacitance vessels
Return blood to the heart
Heart & Lung
Contain the central blood volume – Pump &
Gas exchange function
All together
Closed circuit with pump-oxygenator designed
for distribution & exchange
Mean Arterial Pressure And Its
Regulation
• Regulation of blood flow in arteries
- Intrinsic control
- Extrinsic control
-Neural control
-Hormonal control
* Control of blood vessel radius
* Control of blood volume
Regulation of blood flow in arteries
• It is important to adjust blood flow to
organ needs  Flow of blood to particular
organ can be regulated by varying
resistance to flow (or blood vessel
diameter)
• Vasoconstriction of blood vessel smooth
muscle is controlled both by the ANS and
at the local level.
• Four factors control arterial flow at the
organ level:
- change in metabolic activity
- changes in blood flow
- stretch of arterial smooth muscle
- local chemical messengers
Autoregulation
Definition:
Intrinsic ability of an organ to maintain a constant
blood flow despite changes in perfusion pressure,
independent of any neural or humoral influences
Myogenic Mechanism
• The myogenic mechanism is how arteries and arterioles react
to an increase or decrease of blood pressure to keep the
blood flow within the blood vessel constant
• The smooth muscle of the blood vessels reacts to the
stretching of the muscle by opening ion channels, which
cause the muscle to depolarize, leading to muscle
contraction. This significantly reduces the volume of blood
able to pass through the lumen, which reduces blood flow
through the blood vessel. Alternatively when the smooth
muscle in the blood vessel relaxes, the ion channels close,
resulting in vasodilation of the blood vessel; this increases the
rate of flow through the lumen.
From: AJP - Heart October 2008 vol. 295 no. 4 H1505-H1513
Metabolic Mechanism
• Any intervention that results in an
inadequate oxygen (nutrient) supply for
the metabolic requirements of the tissues
results in the formation of vasodilator
substances which increase blood flow to
the tissues
Metarteriole
Precapillary
Sphincter
Capillary
Relaxation of smooth muscle
Lack of oxygen?
Formation of vasodilators?
Combination of both??
Increased Blood Flow
Intrinsic control of local arterial blood flow
• Change in metabolic
activity
– Usually linked to CO2 and
O2 levels (↑ CO2 
vasodilation ↑ blood flow)
intrinsic control
• Changes in blood flow
- decreased blood flow 
increased metabolic wastes 
vasodilation
• Stretch of arterial wall =
myogenic response
- Stretch of arterial wall due to
increased pressure  reflex
constriction
• Locally secreted
chemicals can promote
vasoconstriction or most
commonly vasodilation
- inflammatory chemicals,
(nitric oxide, CO2)
Extrinsic control of blood pressure
• Two ways to control BP:
- Neural control
- Hormonal control
** Use negative feedback
Neural control of BP
• Baroreceptors: carotid
and aortic sinuses
sense the blood
pressure in the aortic
arch and internal
carotid  send signal
to the vasomotor
center in the medulla
oblongata
• Other information are
sent from the
hypothalamus, cortex
• 
Neural control of BP
• The vasomotor center
integrates all these information
• The vasomotor sends decision
to the ANS center:
- Both parasympathetic and
sympathetic innervate the S/A
node  can accelerate or slow
down the heart rate
- The sympathetic NS
innervates the myocardium
and the smooth muscle of the
arteries and veins  promotes
vasoconstriction
Hormonal control of BP
• Hormones can control blood
vessel radius and blood
volume, stroke volume and
heart rate
• On a normal basis, blood
vessel radius and blood
volume are the main factors
• If there is a critical loss of
pressure, then the effects on
HR and SV will be noticeable
(due to epinephrine kicking in)
• Control of blood vessel radius
- Epinephrine
- Angiotensin II
- Vasopressin (?)
• Control of blood volume
- Anti-diuretic hormone
(vasopressin)
- Aldosterone
• Control of heart rate and stroke
volume
- Epinephrine
Control of blood vessel radius
• Epinephrine: secreted by the
adrenal medulla and ANS reflex
 increase HR, stroke volume
and promotes vasoconstriction of
most blood vessel smooth
muscles.
•
-
• Angiotensin II  promotes
vasoconstriction
-
-
-
Angiotensin II secretion:
Decreased flow of filtrate in kidney
tubule is sensed by the
Juxtaglomerular apparatus (a
small organ located in the tubule)
 secretion of renin
Renin activates angiotensinogen,
a protein synthesized by the liver
and circulating in the blood 
angiotensin I
Angiotensin I is activated by a
lung enzyme, AngiotensinActivating Enzyme (ACE), 
angiotensin II
Angiotensin II is a powerful
vasoconstricted of blood vessel
smooth muscles
Control of blood volume
• Anti-diuretic hormone =
ADH
-
-
Secreted by the posterior
pituitary in response to ↑blood
osmolarity (often due to
dehydration)
Promote water reabsorption by
the kidney tubules  H2O
moves back into the blood 
less urine formed
Control of blood volume
• Aldosterone:
-
-
Secretion by the adrenal cortex
triggered by angiotensin II
Promotes sodium reabsorption
by the kidney tubules (Na+
moves back into the blood)
H2O follows by osmosis
Whereas ADH promotes H2O
reabsorption only (in response
to dehydration), aldosterone
promotes reabsorption of both
H2O and salt (in response to ↓
BP)
Coronary Circulation
Coronary Blood flow – 200-250 ml/min @ 5% CO
SA node:-59% RCA.
38% LCA
AV node:- 90% RCA
10% LCA
Distribution Of Coronary Circulation
Left Coronary Artery
•Ant descending branch.
•Right bundle branch.
•Left bundle branch.
•Ant & post papillary muscle.
•Ant lat left ventricle.
Circumflex Branch
Lateral left ventricle.
Right Coronary Artery
•SA and AV nodes.
•RA and RV
•Post interventricular septum.
•Inter atrial septum.
•Post fascicle of LB
Occlusion in the….
• Anterior descending artery: leads V3-5.
• Left circumflex artery: leads I and aVI.
• Right coronary artery: leads II, III and aVF.
Coronary Perfusion
• Coronary perfusion is unique in that it is
INTERMITTENT rather than continuous
• During contraction, intramyocardial
pressures approach that of systemic
pressures completely occluding the
intramyocardial portions of the coronary
arteries
Coronary Perfusion
• Thus, Coronary perfusion pressure is
usually determined by the difference
between aortic pressure and ventricular
pressure and the left ventricle is almost
totally perfused entirely during DIASTOLE
• As a determinant of myocardial blood flow,
arterial diastolic pressure is MORE
important than Mean Arterial Pressure
(MAP)
Coronary Perfusion
• Decreases in Aortic pressure or increases
in ventricular end-diastolic pressures can
reduce coronary perfusion
• Increases in heart rate also decrease
coronary perfusion because the faster the
heart beats, the less time there is for
diastole for perfusion to take place
Venous Drainage Of The Heart
• Coronary sinus:drains the great
cardiac vein, middle
cardiac vein and the
posterior cardiac vein.
• Anterior cardiac
veins.
• Direct:- arterioluminal,
arteriosinusoidal and
thebasian veins.
Cerebral Circulation
Arterial supply
Posterior
Cerebral
artery
Anterior
Cerebral
artery
Middle
Cerebral
artery
Internal
Carotid
artery
(70% of CBF)
Basilar
artery
Vertebral
artery
30%
of
CBF
Cerebral Circulation
Circle of Willis
Anterior CA
Internal CA
Middle CA
Posterior CA
Basilar A
Vertebral A
Cerebral Artery Areas
1. anterior cerebral
1
2. Middle cerebral
3
2
54
3. Penetrating branches
of middle cerebral
4. anterior choroidal
5
5. Posterior cerebral
Cerebral Circulation
Venous drainage
Cerebral Physiology
• 2% of BW
• 20% of Total body O2 consumption
– (60% used for ATP formation)
• CMR O2 3-3.8mL /100 gm/min
– (50 ml /min in Adult)
• 15% 0f CO (750 ml/min@ 50 ml/100g/min)
• Glucose consumption 5 mg/100gm/min
– (25% of total body consumption/min)
• High oxygen consumption but no reserve
• Grey matter of cerebral cortex consumes more
• Directly proportional to electrical activity
– (Hippocampus & cerebellum most sensitive to hypoxic injury)
Cerebral Perfusion Pressure
• CPP = MAP—ICP (or CVP whichever is greater)
– Normally 80 to 100mm Hg
• ICP is <10 mmHg so CPP primarily dependent
on MAP
• Increase in ICP>30 =CPP & CBF compromise
• CPP<50 slowing of EEG
– 25-40 Flat EEG
– CPP <25 result in Irreversible brain death
Factors Influencing CBF
•
•
•
•
Chemical/metabolic
Myogenic
Rheologic
Neurologic
Chemical/Metabolic
• Cerebral Metabolic Rate
–
–
–
–
–
Arousal
Seizure
Mental State
Anaesthetic
Temperature
• PaCO2
• PaO2
• Vasoactive drugs
– Anaesthetic
– Vasodilators
– Vasopressors
Cerebral Metabolic Rate
• Increased neuronal activity results in
increased local brain metabolism
• Local metabolic factors play a major role in
these adjustments in CBF.
• CMR is influenced by several phenomena
in the neurosurgical environment
– functional state of the nervous system
– anesthetic agents, temperature
Functional State
• CMR decreases during sleep and
increases during sensory stimulation,
mental tasks, or arousal of any cause.
• During epileptoid activity, CMR increases
may be extreme, whereas CMR may be
substantially reduced in coma.
Temperature
• CMR decreases by 6 - 7 %/ oC of
temperature reduction.
• However, in contrast to anesthetic agents,
temperature reduction beyond that at
which EEG suppression first occurs does
produce a further decrease in CMR
The effect of temperature reduction on the cerebral
metabolic rate of oxygen
Temperature on CBF
6-7 % decrease /0C FALL IN TEMP.
 37-42 0C  >42 0C  20 0C
CBF & CMRO2
CMRO2
- ISOELECTRICITY
Partial Pressure of Carbon Dioxide
• CBF varies directly with PaCO2
• The effect is greatest within the range of
physiologic PaCO2 variation.
• CBF changes 1 to 2 mL/100 g/min for
each 1 mm Hg of change in PaCO2around
normal PaCO2 values.
• This response is attenuated below a Pa
CO2 of 25 mm Hg.
• The changes in CBF caused by PaCO2 are
apparently dependent on pH alterations in
the extra cellular fluid of the brain
• Note that in contrast to respiratory
acidosis, acute systemic metabolic
acidosis has little immediate effect on CBF
because the blood-brain barrier (BBB)
excludes the hydrogen ion from the
perivascular space.
• Although the CBF changes in response to
PaCO2 alteration occur rapidly, they are
not sustained.
• In spite of the maintenance of an elevated
arterial pH, CBF returns to normal over 6
to 8 hours because cerebrospinal fluid
(CSF) pH gradually normalizes as a result
of the extrusion of bicarbonate.
• Acute normalization of PaCO2 results in a
significant CSF acidosis (after hypocapnia)
or alkalosis (after hypercapnia).
• The former results in increased CBF with a
concomitant intracranial pressure (ICP)
increase that will depend on the prevailing
intracranial compliance. The latter conveys
the theoretic risk of ischemia.
Partial Pressure of Oxygen
• Changes in PaO2from 60 - 300 mmHg have little
influence on CBF.
• When the PaO2is less than 60 mm Hg, CBF increases
rapidly .
• At high PaO2values, CBF decreases modestly.
• The mechanisms mediating the cerebral vasodilation
during hypoxia are not fully understood, but they may
include neurogenic effects initiated by peripheral and/or
neuraxial chemoreceptors as well as local humoral
influences
• At 1 atm O2,CBF is reduced by 12 percent.
Myogenic Regulation
Autoregulation refers to the capacity of the cerebral
circulation to adjust its resistance in order to maintain CBF
constant over a wide range of mean arterial pressure
Neurogenic Regulation
• There is considerable evidence of extensive
innervation of the cerebral vasculature.
• The density of innervation declines with vessel
size, and the greatest neurogenic influence
appears to be exerted on larger cerebral
arteries.
• This innervation includes autonomic,
serotonergic, and vasoactive intestinal peptideergic (VIPergic) systems of extra-axial and intraaxial origin.
Viscosity Effects
• Blood viscosity can influence CBF.
• Hematocrit is the single most important
determinant of blood viscosity.
• In healthy subjects, hematocrit variation
within the normal range (33-45%) probably
results in only trivial alteration of CBF.
• Beyond this range, changes are more
substantial.
"a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions"
oxygen
delivery
muscles
thirst
kidney
ADH
control
local blood
flow
control
autonomic
control
heart rate…
capillary
membrane
dynamics
circulatory
dynamics
angiotensin
control
aldosterone
control
tissue fluids,
pressures,
gel
pulmonary red cells,
dynamics viscosity heart
hypertrophy
electrolytes
& cell
water
Guyton, Coleman, Granger (1972) Ann. Rev. Physiol.
Guyton's modular Systems Model for blood pressure regulation
Good Luck