CARDIOVASCULAR

Functions of cardiovascular system

Nutrients body
Fuel cells
Oxygen cells
Removal of waste products
Circulation of hormones and immune cells and antibodies
Regulation of electrolytes, pH
Water balance
Thermoregulation
Who doesnt need a cardiovascular system?
Small organisms can depend on diffusion
o Amoeba (1-2 mm)
Cardiac muscle cells 100 micrometers long, 10-20 micrometer
diameter
o Blood vessels (capillaries) between cardiac cells
Within 10 microns have 3-4 blood vessels
Diffusion is sufficient
o 1:1 ratio between blood vessel to cardiac cell
Diffusion: Ficks Law
Flux= flow/unit area= D x concentration gradient
C C
flux=D ( out
)
o
d

o D= diffusion coefficient
Depends on the substance it is diffusing AND
through what substance
Flow= Flux x Area
C C
flow=D out
A
o
d

o Total area of alveoli= tennis court

Cardio-vascular system
Heart= pump
Pipes= vessels
Fluid= blood
Insect circulation

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Vessel filled with hemolymph

Hemolymph goes back into circulation
through holes (ostium)
OPEN circulation

Piscine (fish) circulation

Closed circulation
Single loop, 2 chambers
RED= oxygenated blood
Amphibian & reptilian
circulation
Closed circulation
Double loop, 3 chambers
Amphibians can breath through their
skin
Blood does not mix very much
Avian and mammalian circulation
Closed circulation
Double loop, 4 chambers
LEFT= systemic: from lungs heart body
RIGHT= pulmonic: from body heart lungs
Hemodynamics
The movement of blood
Forces involved in the circulation of blood
Volume, flow, pressure, resistance
Volume
Blood volume= 5 L (7.5% of body weight)
o 1 unit of blood= 450 mL
o Numbers for health young 75 Kg man who is lying flat
Most of the blood (60%) in the venous system (capacitance)
20% in the arterial system (resistance)
10% in the lungs
10% in the heart
Flow
Left & right heart pumps blood out at 5000 mL/min (cardiac
output)
Venous return= return of blood from lungs/body to heart
(5000mL/min)
Biggest flow of blood is to muscles

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o Even when they are not moving (biggest organ)
Flow measurement
Volume
Flow=

Time

Unit: mL/min or L/min

To compare: normalize mL/min/100gm of tissue
Because different organs are different sizes

Cross sectional area and flow velocity

Flow=Area MeanVelocity

o Mean velocity because velocity is not necessarily the same

at all points in cross section
Unit: cm3/sec

Number and dimensions of vessels

As you move away from the heart capillaries
o Number increases
o Diameter decreases
o Length decreases
Opposite as capillaries heart
Aorta arteries arterioles capillaries venules veins
vena cava
Total cross sectional area and flow velocity
As you move toward capillaries
o Area increases and velocity decreases
o Flow remains the same
Advantages to big area= big surface area= more flow to cells
o To low velocity= more time to exchange

Pressure

Pressure=

Force
Area

Unit: Pa= N/m2

Blood pressure= 120/80 mmHg
Central venous pressure= 5-10 cm H2O

Pressure gradient

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Longitudinal pressure gradient will generate a flow

Hydrostatic pressure: pressure exerted by a fluid at equilibrium
at a given point within the fluid, due to the force of gravity
Hydrostatic Pressure=gh
o
1 cm H20 = 0.98 kPa (dont need to know this)
Independent of area
Atmospheric pressure
o Zero= atmospheric pressure= 760 mmHg

Stephan Hales (1733)

Glass tube into carotid artery of the horse
Blood pressure= height that blood goes up to
o Blood pressure= hydrostatic pressure
o Blood has about the same density of water
Mercury is 14 x as dense as water
1cm Hg= 13.6 cm H2O
This is a direct method of measurement (critical condition in
patients)
Mercury Sphygmomanometer
Column of mercury + cuff
Pressure of cuff= blood pressure= hydrostatic pressure of
mercury
o Now it is replaced with a analog gauge
1 mmHg= 14 mmH2O= 1.4 cm H2O
Measure central venous pressure=right atrial pressure (very close)
Tip of catheter in right atrium (right atrial pressure=CVP)
Pressure of blood at base of manometer= hydrostatic pressure of
saline
o Fill saline higher than excepted it will fall into heart
CVP ~ 5-10 cm H2O
Perfusion pressure
P=P P out

P=P arterial Pvenous

Since Parterial Pvenous

o Around 100 mmHg vs. 5 mmHg

P
Flow=
R

P=P arterial

o Like Ohms Law: V=IR (V=pressure, I= pressure, R=

resistance)

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Laminar or parabolic flow

Layers of blood flowing past each other
Also called smooth flow
Closer to wall= slower (parabolic)
Because they are moving past each other friction
o Friction= heat= loss in pressure
o As you move down the tube less pressure
o This is called internal resistance (viscosity)
Poiseulles Law
8 vL
R= 4

r
o v= viscosity of the fluid (only valid for laminar flow)
Control of vessel resistance
1
R

radius

Controlled by local metabolites, innervation (ANS), hormones

Increase radius= decrease resistance=increase flow

Resistance

Series:
Parallel:

P=Flow ( R 1+ R 2)
P=Flow (

1 1
+ )
R1 R2

o That's why it is in parallel can add vessels without

increasing resistance and thus increasing pressure

4 chambers of the heart

Right atrium (blood from body)
Right ventricle (blood to lungs)
Left atrium (blood from lungs)
Left ventricle (blood to body)
The great vessels
Pulmonary trunk, left & right pulmonary artery
o From right ventricle to lungs
Aorta

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o From left ventricle to body

Vena cava (superior, inferior)
o From body to right atrium
2 Right/2 Left pulmonary veins
o From lungs to left atrium

Dividers/walls
Inter-atrial septum (between atria)
Inter-ventricular septum (between ventricles)
Left ventricular free wall
Right ventricular free wall
Cardiac valves
Atrial ventricular values
o LEFT: mitral value (bicuspid)
o RIGHT: tricuspid value
Pulmonary value (semilunar) (right ventricle/pulmonary trunk)
Aortic value (left ventricle/aorta)
Values sit in a fibrous ring (NOT muscle)
Papillary muscles and chordae tendinae
Papillary muscle: cylinder of muscle that comes out of the wall
It attaches to leaflet of values by chordae tendinae
When ventricle contracts chordae tendinae pull down on
leaflets and prevent prolapsing in the atrium and keep value
closed
Papillary muscle rupture mitral regurgitation (value
replacement)
Other terms

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Thin layer of cells on the inside of the heart:

endothelial cells
o Called endocardium (endothelium)
Pericardium: heart sits in it
Pericardial fluid: between pericardium and
epicardium
o Too much fluid (pericardial
tamponade)= push ventricular muscle=
decreased volume of blood in heart=
decreased cardiac output= decrease
blood pressure
o Pericardial effusion= collection of fluid
in pericardial sac

Activation sequence of the heart

Specialized cardiac muscle cell that carries
action potential
Sinoatrial node: spontaneously starts action
potential (activation wave)
Atria beat
Action potential cannot travel through fibrous tissue
Atrioventricular node bundle of his left/right bundle branch
purkinje fibers(line endocardium) from subendocardium
through thickness of heart subepicaricardiumboth ventricles
beat
Intercalated disc
Hold to cardiac cells together
Specialized structures in the intercalated disc
o Called nexus/gap junction: two cell
membranes come very close
together
o Hemichannel + hemichannel= gap
junction
6 subunits with pore in the
middle (cytoplasm)
BIG channel: any ion can get
through
Action potential can propagate
Local circuit currents

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Both
intra- and
extracellular
flow of
current is
necessary

Membrane is
an
insulator
No charge
= no potential
Local current is measured by ECG
* ALL positive ions (not just Na and K) AND ALL negative ions
Electrocardiogram (ECG)
Electrocardiogram: the printed graph
Electrocardiograph: the device that measures it
Voltmeter to measure extracellular voltage
o Measure the different in two points
Patient hooks up with the patient 5 leads (copper wire)
ECG waves and complexes
Amplitude= 1 mV in
interstitial space at the
surface (vs. 100 mV for an
intracellular recording)
ONLY local circuits: only
depolarization OR
repolarization
Waves
Before P wave= activation
of SA node (too small)
P wave= atrial excitation
(1/2 right, left)
Halfway through P = AD node (slowly)
Between P and Q= bundle of his, bundle branches, purkinje
Q= septum, R= left and right ventricular free walls
T= ventricular wave of depolarization
Leads
Electrode itself RA lead

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Combination of electrodes taken to the voltmeter Lead I

Bipolar limb leads (Willem Einthoven)

I= Left arm lead (+) and right arm lead (-)
II= left leg right arm
III= left leg left arm
9 more leads: unipolar
o aVR= right arm
o aVL= left arm
o aVF= left leg
o V1-V6: recorded in the chest (heart from different angle)
Ventricular action potential
Resting potential is -90 mV vs.
-60 of neuron
Long plateau
Duration: 300 ms action
potential (vs. few seconds of
neuron)
Ionic basis underlying the ventricular
AP
At rest, permeability K is much
higher than Na or C So resting potential (-90mV) is close to Ks (100mV)
Upstroke of action potential (depolarization) Na flow into cell
(1ms) INa (fast inward Na current)
o K channels close
Top of upstroke: Na channel closes
After upstroke: Ca channels open Ca flows in (depolarization)
K channels open: K leaves cell repolarization
o Different K channels open and close at different times to
produce eventual repolarization of cell
Plateau= battle between Ca and K (fluxes are almost equal)
Repolarization= Ca channels close
Sinus node action potential

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NO resting membrane
potential
No Na current SO Ca generates
the upstroke

Fast vs Slow APs

Slow (upstroke=1-10 V/s)
o SA node, AV node
o Conduction velocity=
0.01-0.05 m/s
Fast (upstroke 100-1000 V/s)
o Everywhere else in the heart
o Conduction velocity= 0.5-5 m/s
ECG and Ventricular AP
Atrial repolarization occurs during QRS (small)
PR segment is long because AP in AV node is SLOW
Normal sinus rhythm
Sinus bradycardia: rate is LESS than 60/min
o Atheles can have this resting potential
o Sleeping
Sinus tachycardia: rate is MORE than 100/min
o Physiologic= exercise
Sinus arrhythmia: on inspiration= increase rate
o On expiration= decrease rate
o Does not occur when you age

2:1 Atrioventricular block

every other ventricular is blocked
o for every 2 atrial there is 1
Problem: ventricular activation heart rate is HALF
o HALF cardiac output
o Some people are ok with this

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Block can get worse can become complete
atrioventricular block
Treatment= pacemaker that beats ventricles

Complete atrioventricular block

2nd picture: subsidiary pacemakers appear

o Activate ventricular action potential (TOO SLOW)
NOT reliable
o Treatment= put in an electronic pacemaker

Premature ventricular contraction

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QRS occurs
at the peak of the last T wave
o Ectopic beat in the ventricles probably from an ectopic
pacemaker
Ectopic means in the wrong place

Rapid
rhythm in
the

ventricles (V tach)
o QRS/T every 0.2 s 5 times/ second
o Cardiac output=0 because there is no time for ventricle to
pump
V. Fibrillation low amplitude cannot return to normal
o Use AED= automated external defribrillator
o Big shock can bring one back to normal sinus

Mapping of cardiac electrical activity

Epicardial= on the outside of the heart
Endocardial= balloon on inside of the heart

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Reentrant ventricular tachycardia

Line= activation wave front
This patient had v. tach 3 months prior
o No v. fib
Scar tissue= dead heart cells replaced
by fibrous tissues= anatomical
obstacle
Circus movement reentry muscle
excited a lot gets tired
o Block of propagation multiple
wavefronts= V. fib= no pumping
o George Ralph Mines found this
Pulmonary vein isolation for treatment of atrial fibrillation
If atrial does not pump ventricles can still pump
PAC coming from pulmonary veins (ectopic focus)
o Pulmonary vein isolation burn/freeze around pulmonary
veins muscle cells replaced by fibrous eclls
In half of patients= a. fib comes back

Excitation contraction coupling

Ca into cell/ via T tubule into cytosol

Ca binds to ryanodine receptors on the SR

Ca channels on SR open LOTS more Ca into cytosol
Ca binds to troponin complex= contraction

Mechanical activity
Mechanical activity lags behind electrical activity

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Activation NOT contraction

Pulseless electrical activity= electro-mechanical dissociation
o No mechanical activity but there is electrical

The cardiac cycle

Systole= contraction (1/3 of the time)
o Isovolumetric ventricular contraction
Pressure closes AV value
AV= Closed
Aortic/pulmonary= closed
o Ventricular ejection
Pressure in ventricles > aorta/pulmonary A/P opens
AV= closed
Aortic and pulmonary valves= open
Diastole (2/3 of the time)
o Isovolumetric ventricular relaxation
Pressure in aorta/pulmonary> ventricles A/P closes
AV= closed
A/P= closed
o Ventricular filling
Pressure in atrium> pressure in ventricle AV open
AV= open
A/P= closed
THEN AV node activates and atrium contracts

Wiggers diagram of the left heart

Heart sounds:
o 1st= closing of both AV
o 2nd= closing of both aortic and
pulmonary value
Stroke volume, ejection fraction and cardiac
output
Stoke value= 120-50-70 ml
Stoke Volume=End Diastolic VolumeEnd systolic Volume
o

Ejection Fraction= 70/120= 60%

Stroke Volume
Ejection Fraction=
o
End DiastolicVolume
o Good measure for people with bad hearts

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Cardiac output= 70 x 70= 5L/min

o

Cardiac Output =Heart Rate Stroke Volume

Right heart
Peak pressure in left heart= 120 mmHg
o In right heart= 25 mmHg
Starlings law of the heart Frank-Starling Mechanism
Exercise increase end diastolic
volume increase stroke volume
o If you stretch cardiac muscle, it
will contract more strongly
Preload: the amount of stretch in the
muscle prior to contraction
o Preload goes up when
ventricles stretch
o Measure by EDV or right atrial pressure

Normal values vs. abnormal values

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Abnormal valves
Stenotic valve: not completely open (calcium deposition)
Insufficient valve: leaky value (some backflow)
Some are pathologic, most are benign
Blood pressure LEFT arterial blood pressure
Maximum= systolic pressure (120)
Minimum= diastolic pressure (80)
Pulse pressure= systolic-diastolic= 40
Mean arterial pressure (MAP)= diastolic + (1/3) pulse pressure
1
MAP=diastolic pressure+ Pulse pressure
o
3
Measurement of BP
Direct
Indirect: palpation, auscultation, oscillometry
o All use aneroid sphygmomanometer
Inflating bulb, cuff, aneroid gauge, needle valve
Method of palpation
High pressure in cuff> artery= stop flow
First pulse: systolic blood pressure
Method of auscultation
Use stethoscope
High pressure in cuff> artery= no flow = no sounds
Systolic> cuff= open a bit= turbulent flow= Kirchhoff sounds
o Marks systolic pressure

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Diastolic>cuff= fully open= no sounds

o Marks diastolic pressure

Oscillometry
Little pulses = hit the cuff = pressure in cuff increases
These start before systolic and end after diastolic
o Algorithm can fix this
Don't need to be trained
Total peripheral resistance
Blood Pressure Mean =Cardiac output total peripheralresistance

Heart rate Stroke volume Total peripheral resistance

Perfusion pressure and flow

Perfusion Pressure
Flow=

Resistance

Organ can adjust the flow according to need of BP

Body tries to keep flow constant (AUTOREGULATION)
o Minimize fluctuations in MAP (NEURO-HORMONAL
CONTROL)

Pulmonary Vascular resistance

Systemic circulation
o Mean pulmonary artery pressure = 15 mmHg
o Pulmonary vein pressure = 5 mmHg
Pulmonary PERFUSION pressure = 10 mmHg
Pulmonary pressure SMALLER than systemic (by 1/10)
o Flow remains the same
o SO pulmonary resistance (PVR) is SMALLER than systemic
(TPR)
Autoregulation of flow
Organs regulate flow without neuronal or hormonal input
Occurs particularly in brain, kidney, and heart
Two mechanism of
autoregulation
Two mechanisms operate
concurrently
The opposite also
happens
Protect flow from small
changes in pressure

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Local metabolic control (completely different from autoregulation)

PREVENT change in pressure
o Low adjusts to metabolic need
Occurs in skeletal muscle, cardiac muscle, brain
(Active) Hyperemia: increase in the flow of blood
o eg//seizure
Same mechanism from autoregulation, but different goal
Parasympathetic control of heart rate
Starts in medulla oblongata
Axons in vagus nerve (pre-ganglionic nerve)
Synapse in ganglion (in the fat of the heart)
o Ach nicotinic receptor
Postganglionic axon to SA node
o Ach muscarinic receptor
o Open K channel SLOW heart rate
K leaves cell voltage becomes MORE negative
Drugs: atropine blocks muscarinic receptor: increase heart rate
Sympathetic control of heart rate
Start in spinal cord
Preganglionic synapse with postganglionic at ganglion
o Ach nicotinic
Postganglionic synapse with SA node
o Norepinephrine (noradrenaline) beta-adrenergic receptor
o INCREASES heart rate
Drugs: beta-agonist activate receptor INCREASE heart rate
o Beta-blocker DECRESE heart rate
Change in rate of SA node

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Sympathetic
control of
contractility
Same as
control of heart rate except it synapses with ventricles increase
of SA node
Increases the strength of contraction
o Duration of systole decreases
o SHIFT frank starling law to the LEFT
BOTH frank-starling and increase of contractility
occur when you exercise
Same drugs can be used

Sympathetic control of vessel tone

NOT in capillaries
Postganglionic synapse with blood vessels
o Norepinephrine on ALPHA-adrenergic receptor
Constrict vessels increase blood pressure
o BECAUSE MAP= CO x TPR
Drugs: alpha-agonist, alpha blocker
Sympathetic control of adrenal glands
DIRECTLY from spinal cord to adrenal glands Ach
RELEASES catecholamines
o 2/3 epi and 1/3 norepi BOTH are alpha and beta agonists
BP systems
Different time scales
o Baroreceptor acts very quickly
o Renal-body fluid pressure control is slow
Kidney takes out water depending on BP
Different feedback gains
o Kidney has 100% gain, extremely strong reflex

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o Baroreceptor are a strong reflex

Different ranges of pressure
o Baroreceptor (around MAP)
o CNS ischemic response (less than 60mmHg)

Baroreceptors
Reflex that senses pressure
In carotid sinus and aortic arch STRETCH receptors
Every heart beat it stretches action potentials
o Higher pressure= higher firing frequency= decrease BP
o Increase or decrease sympathetic/parasympathetic
Heart rate, contractility, vessel tone
IF you cut the nerve (baroreceptor denervation)
o Very high and very low pressures (labile)
o THUS baroreceptor reflex is called the buffer reflex
Long term MAP is unchanged
Kidney, blood volume and BP
Increase in BP= increase pressure diuresis (urinary loss)=
decrease plasma volume
Decrease end diastolic volume frank starling mechanism
Dcrease stroke volume, decrease cardiac output= decrease BP
Diuretic= reduce BP

The renin-angiotensin-aldosterone (RAA) system

If BP falls: kidney produced more renin (enzyme)
o Act on angiotensinogen (liver) angiotensin I
o ACE in lungs angiotensin II
Cause constriction of arterioles increase TPR= increase BP
Cause brain to secrete ADH
o Vasoconstriction
o Kidney keeps more water increase BP
Causes adrenal glands to secrete aldosterone
o Decrease sodium loss= decrease water loss= increase BP
DRUGS: ACE inhibitor= decrease angiotensin II= decrease BP
o AT-II receptor blocker= decrease BP
o Aldosterone antagonist= decrease BP
o Renin inhibitor= decrease BP

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Orthostasis
Arterial blood pressure: doesn't change much
o Slight rise in diastolic, slight drop in systolic (10 mmHg)
o For 10 s: immediate drop in BP
Due to hydrostatic pressure
o Mean arterial blood pressure remains the same
Central blood volume: from 1.2 0.9 L
o Blood is pooled in lower extremities
Right atrial pressure: 5.1 0.2 mmHg
o Right atrium not as filled, because blood in feet
Stroke volume: 100mL 50 mL
o Atrium is not as filled
o Frank starling mechanism AND there is less blood
o Despite increase in contractility (baroreceptor)
Cardiac output: 6L/min 4.5 L/min
Heart rate: 60 90
o To increase cardiac output after stroke volume is cut in half
o CO= HR x SV
TPR: increased (INCREASE constriction)
o Blood flow to forearm decrease (doesn't happen in
brain/heart)
o To maintain MAP MAP= CO x TPR
Orthostatic/postural hypothesion
If system does not work
BP falls enough faint
Muscle pump in orthostasis
Everything goes back to levels of lying flat
Constricting muscles in calf
o Effect is due to venous valves
o One way valve to prevent backflow
Pressure in vein increase opens next valve, closes
last valve
Very important in exercise
Venous pressure while standing
High pressure in veins water goes into interstitial space
Blood volume is reduced
Less frank-starling decrease TP
Muscle pump lowers venous pressure
o Less blood in veins (80 25)

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Starling forces
Arterial end: net filtration pressure= 10 mmHg
Venous end= -10 mmHg
Lymph flow= 4L/day

Exercise
HR increases (linearly)
o Max heart rate= 220- age
o Increase by x3
o Due to sympathetic ervous system
Stroke volume: increase (due to contractility)
o SV decreases at high HR because heart is pumping too fast
for the ventricles to fill
Cardiac output increases by x 3
o Due to HR increase rather than SV
CO= HR x SV
Arterial pressure: increase by x 1.2
TPR: decreases by 0.4 because MAP= CO x TPR
o Using more of muscles waste products dialation
Oxygen consumption x 9
o Because CO x3 and arteriovenous oxygen dif increase by
x3
Arteriovenous oxygen difference: increase by 0.3
o Fick principle: V o 2=Cardiac output av O2

Oxygen consumption= cardiac output x a-v different

in oxygen difference

Regional blood flow in exercise

Muscle x 12
Heart x 3.5
Skin x 5 (so you can loss heat to the atm)

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Kidney x 0.6, abdominal organs x 0.5

o Aloow for CO to go where it is needed
o Brings TPR up to keep BP up
TOTAL x 3.5
o Super athelete= 35 L/min ( x7)

Endurance training
Can go to higher work load and a higher cardiac output
o CO= HR x SV
o Trained: lower heart rate for same work load
Can reach higher max work load before max heart
rate
o SV increase due to hypertrophy of ventricular muscle
Cardiac cells grow in size