cardiovascular physiology
TRANSCRIPT
Cardiovascular Physiology - Samantha Bray - Western College of Veterinary Medicine
A. Overview of Cardiovascular System
Function of the Cardiovascular System
I. Transport O2 to tissues and CO2 to the lungs Nutrients, Wastes, Hormones Heat distribution
II. Adjusts blood supply in different physiological states (important for flight/fight response). During flight it redirects blood from kidney, stomach, etc – to the muscles and heart.
III. Kinetic energy to maintain circulation (via Heart). IV. Metabolism
Endothelial cells: Angiotensin I Angiotensin II (powerful vasoconstrictor).
CV system divided into: Pulmonary Circulation and Systemic Circulation
Pulmonary Circulation
Pulmonary veins take blood from the lungs to the left side of the heart. Pulmonary artery takes blood from the heart to the lungs.
FunctionsI. Site of gas exchange
II. Reservoir for left side of the heartIII. Metabolic function
Systemic Circulation
FunctionsI. Delivers nutrients to tissues
II. Removes wastesIII. Metabolism
Division of Cardiac Output 5% goes to coronary arteries 30% goes to the gut (slightly higher in ruminants – more tissue there) 20% goes to the kidney 1% goes to bronchial tissue 15% goes to upper body (forelimb, head, neck area).
Heart Anatomy Left and Right Side are two separate chambers divided by the septum. Covered by the Pericardium
o Restricts the movement a bito A bit of fluid b/w sac and hearto Pericarditis: Inflammation increase the fluid between the sac and heart.
Results in Cardiac Tamponade – restricts the pumping action of the heart. Seen in cattle as hardware disease.
In mammal’s weight is 0.6% of total body weight (based on size of animal and genetics – greyhounds have slightly larger hearts than normal).
o 0.8% in birds
Ventricles are the main pumps of the heart. o Right ventricle 1/3 of the mass of the left ventricle. The left ventricle pumps
against a much higher resistance. Right ventricle pumps blood into the lung (low resistance).
Atria are the primer pumps.
Valves of the Heart
1. Atrioventricular Valves (AV)a. Right = Tricuspid Valveb. Left = Mitral ValveBoth valves have chordae tendinae – anchor the AV valves when pressure increases in the ventricle – prevents the opening of the valve in the opposite direction.
2. Semilunar Valvesa. Right = Pulmonary Valve: goes
from right ventricle to the pulmonary artery.
b. Left = Aortic Valve: goes from left ventricle into the aorta.
Function of Valves: allow one-way flow of blood (prevents backflow). All valves act passively – no stimulus (AP) needed – just respond to pressure differences on either side of the valve.
Right side of the heart contracts at the same time as the left side of the heart. Ventral and Atrial syncytium are separate from one another.
Figure 1. Mammalian Heart Anatomy
Flow of BloodSuperior vena cava & Inferior vena cava R atrium Tricuspid Valve R ventricle Pulmonary Valve Pulmonary Artery Lungs Pulmonary Veins L atrium Mitral Valve L ventricle Aortic Valve Aorta Tissues
Avian Heart – has simpler valves and smoother walls on the inside. Ventricles have a lot more muscle and a smaller chamber size. Apex of heart more pointed.
Tissue Layers in the Heart1. Endocardium
a. Continuous w/ endotheliumb. Prevents blood clottingc. Helps moving it alongd. Thin
2. Myocardiuma. Muscle (thickest layer) – does
the pumping3. Epicardium (AKA Pericardium)
a. Outside CT layerb. Protective
Myocardium Cells1. Myocardial working cells (99%)
a. Cardiac Musclei. Has intercalated discs (gap
junctions) that serve as electrical synapses – ions can flow from 1 cell to another (w/o going through a chemical synapse).
ii. Allow cardiac cells to contract as one unit (syncytium). 2. Specialized conductive fibers (1%)
a. Generate action potentialb. Move AP through heart in a specific manner.
Figure 2. Avian Heart AnatomyFigure 2. Avian Heart Anatomy
Figure 3. Layers of the Heart
Electrical Properties of Cardiac Muscle
Which ion is most responsible for the resting membrane potential? Potassium.
Resting membrane potential (-85 mV to -90 mV)
Em=61.5 log Pk[K]o + PNa[Na]o+PCl[Cl]i/Pk[K]i+Pna[Na]i+PCl[Cl]o
Channels Present – voltage dependent
1. Fast Na+ Channelsa. Activation and Inactivation gate
2. Slow Ca++/Na+ Channels (AKA L-type channel = long-lasting channel)a. Opens at -35 mVb. Opens and closes slowly
i. Also has T-type (transient) – opens and closes quickly – of little importance.
3. K+ channelsa. Transient outward (ito) - efflux: K moves from inside to outsideb. Delayed rectifying (ik) – efflux: K moves from inside to outside (responsible for
repolarization in nerve/skeletal muscle/heart).c. Inward rectifying (ik1) – closed when +mV, influx>efflux at –mV (potassium
moves from outside to inside).
Phases of Action Potential
0. Depolarizationa. Stimulus opens fast Na channels (sodium rushes
in).b. Ca (L-type – long lasting) channels opens at -35
mV (calcium moves in). 1. Recovery
a. Transient efflux of K+ (transient outward K channels)
2. Plateaua. Maximal opening of Ca (L-type) channels (Ca++ moves in)b. Some K+ efflux (K moving out) (ito, ik, ik1)c. Low permeability at +mV for ik1d. Balance between K+out and Ca++ in – so that membrane potential doesn’t change
much – giving rise to plateau3. Repolarization
a. Permeability for K+ increases a lot (ito, ik1, ik)i. Ik channel most importantii. Net K+ efflux (moving out)
4. Stabilizationa. Continued K+ efflux
b. Na+/K+ pump returns Na/K ions to normal (3 Na out : 2 K in)c. Ca++ leaves cell in exchange for sodium (1 Ca out : 3 Na in)d. Ca++ efflux ATP driven pump
Refractory Periods1. Absolute refractory period (ARP):
absolutely no way another action potential can be initiated.
0.25-0.3 seconds no strength of stimulus causes an AP
2. Relative refractory period (RRP): can be stimulated with a very large stimulus. 0.05 seconds
Effect of long refractory period in cardiac muscle Prevents tetanus Allows heart to act as a pump (contract, relax, fill).
Excitation Contraction Coupling: how an AP in the membrane leads to contraction.
Working Cells: cardiac muscle cells – with intercalated disks: allow muscle to act as a syncytium – allows AP to pass and force.
Cardiac muscle lots of mitochondria T-tubules (extension from extracellular
space & are better developed in cardiac muscle compared to skeletal muscle). The T-tubules run down the Z-line.
Sarcoplasmic reticulum is a bag that holds the calcium (less developed compared to skeletal muscle). SER can come very close to the T-tubules – and forms a diad structure.
Excitation-Contraction Coupling1. AP travels down sarcolemma and into T-tubules2. Calcium enters cell from ECF including from T-tubules L-type calcium channel
a. 30% of required calcium comes from the ECF/T-tubules.3. Calcium is released from sarcoplasmic reticulum (ryanodine receptor)4. Calcium binds with troponin.5. Conformational change in tropomyosin6. Myosin binding sites on actin are exposed7. ATP myosin removed (unhinges myosin so it can do a power-stroke). 8. Cross-bridge cycle continues
Relaxation – AP ends1. Calcium reuptake by sarcoplasmic reticulum2. Calcium leaves cell & goes back to the ECF in exchange for sodium (3 Na in, 1 Ca leaves)
a. Na/K ATPase maintains the gradients needed for the Na/Ca exchanger to work. 3. Calcium pump
Specialized Conductive Fibers (1%) SA node internodal tracts AV node bundle
of His Right & Left bundle branches that go to left/right side of the heart Purkinje fibers
Species Differences in Depth of Purkinje Fibers Subendocardial (just below the endocardium of the
ventricles)o Cats, dogs, rodents, humans.
Whole Free Wall (much deeper, go through the whole free wall).
o Birds, horses, ruminants. o Changes the ECG
Functions of Specialized Conductive System1. Automaticity – the ability to generate its own action potential (heart can keep beating
w/o outside influence)2. Rhythmicity – heart beats in a rhythmic manner – specialized conductive system spreads
current through the heart in a special way (right order/timing).
Electrical Properties of Cardiac Muscle Specialized conductive fibers – SA and AV node
Slow Response AP Resting membrane potential is -60 mV to -65 mV (closer to 0) Only has 3 phases
o Phase 0 – depolarizationo Phase 3 – Repolarizationo **Phase 4 – Pre-potential (AKA Pacemaker potential or Diastolic depolarization)
Responsible for automaticity By itself it creeps up to 0 mV to generate an AP.
What’s happening in these Phases?? Phase 4 - Slow depolarization
o Movement of K+ outward decreases with time (left over from repolarization) – iK channels
o Movement of Na+ (not fast Na channel, iF) inwardo Movement of Ca++ inward – near end of 4 (L-type and T-Type)
Phase 0 – Depolarizationo Opening of L-type Ca++ channels – begins at -35 mV to -40 mV.o NO INVOLVEMENT OF SODIUM
Phase 3 – Repolarizationo Opening of the K+ channels
Functions of Specialized Conductive System
1. Automaticity a. SA node – fastest generation of APb. AV node – can also act as a
pacemaker – but is slowerc. Areas of Purkinje system
Why is the SA node the pacemaker? Highest rate of diastolic repolarization Overdrive suppression
o AV node becomes hyperpolarized when encountering action potential from SA node
o Prevents AV node from firing by itself.
How fast does SA node fire? Large animals are slow (elephants ~30
beats/min) Younger animals have faster heart rates (calf
~150 beats/min, whereas bull ~50 beats/min). Birds have very fast heart rates (bar-headed
goose = 466 beats/min).
Conduction Velocity
Depends on: Rate of rise of 0 phase (depolarization)
o Faster the rate of rise = faster the velocity Amplitude of AP
o If AP is large there is a faster conduction velocity
Diameter of muscle fibers Number of gap junctions b/w fibers.
o More gap junctions = faster velocity
Conduction velocity decreases at the AV node and the bundle of His Cause:
o Smaller diameter fiberso Branching o Fewer gap junctions b/w fibers
Effecto Allows atria to contract before the ventricleso Protects ventricles from increased rate of contraction – sometimes atria contacts
too fast.
o May have conduction block here (BAD). Site Average conduction velocity
(m/sec)Time for Transmission (s)
SA to AV node 0.8-1.0 0.04AV node to bundle of His 0.05 0.11AV bundle to end of Purkinje fibers
2.0 0.03
Ventricular muscle 0.4-1.0 0.03
Rapid spread from SA to AV node – allows atria to contract.Slow spread from AV node to bundle of HisFast conduction from AV bundle to end of Purkinje fibers.
Significance of Specialized Conductive System Generates AP Carries AP through heart Allows rapid/synchronous contraction of atria Carries AP from atria to ventricles Allows atria to empty into ventricles before the ventricles contract
o protects ventricles form increased rate of contraction Allows rapid and synchronous contraction of the ventricles.
Abnormalities Ectopic Pacemakers
o Abnormal locations (where you don’t want them)o Develop after injury, over stimulation (stress/caffeine).
Heart Blocko Interference with conductiono Av node and Bundle of Hiso Bundle Branches
Effect of Change in Ion Concentration on the Action of the Heart
CALCIUM
Increase in ECF calcium Happens during kidney disease, from drugs Increases force of contraction (+ inotropic effect)
o Can stop heart in systole (when too much calcium comes in). - Do not want to have a sustained contraction because then it cant
fill/empty as needed.
Decrease in ECF calcium Happens during milk fever in cows. Decreases force of contraction (- inotropic effect) Dissociation b/w excitation (action potential) and contraction
Inotropic = modifying the force or speed of contraction of muscles
Flaccidity – the contraction that occurs is weak.
SODIUM
Increase in sodium ECF Increased calcium removal from the cell
o Increases rate of sodium calcium exchanger Decreases force of contraction (- inotropic effect)
Decrease in sodium ECF Decreased calcium removal from the cell
o Sodium calcium exchanger doesn’t work as well – more calcium is left in the cell Kinda good (can increase contraction of the heart) However, not enough sodium = loss of syncytium --> hard to get AP from
one cell to another Increased force of contraction (+ inotropic effect)
o Can result in fibrillation (loss of syncytium) When the cells become independent; work on their own.
POTASSIUM
Increased potassium in ECF Bring resting membrane potential closer to 0
o Decreases rate of both depolarization and conduction velocity because fast sodium channels have been inactivated because of rate
of rise of the slope and the height of the action potential Flaccidity Arrhythmias Can be utilized as a method of euthanasia (slowly decreases heart rate).
Decreased potassium in ECF Hyperpolarization Interferes with Na/K pump: do not have enough potassium to drive the pump – keeps
sodium in the cell & results in less sodium on outside leaves calcium inside the cell & can increase the force of contraction
less Na on outside therefore more calcium on the inside increases force of contraction
May increase the size of the sodium channel Prolonged repolarization, abnormal pacemaker activity leads to arrhythmias
Different parts of the heart respond to these different potassium concentrations differently.
ELECTROCARDIOGRAM (ECG)
- Non-invasive way of seeing what is going on in the heart. - Movement of ions in the heart can be detected on the surface of the body – tells us how the electrical currents are spreading through the heart. - Produces a wave: with P wave, QRS complex and a T wave.
What are you measuring?
Electrical activity of one point on the surface with respect to another point on the surface.
o Recording electrode versus reference electrode.
From where are you measuring the electrical potentials?
Lead systems Observation platforms looking at the heart. Two broad categories:
o Bipolar leads: look at one point on the body with respect to another. o Unipolar leads: looks at one point on
the body with respect to 0. Chest leads – most common –
extend from V1 to V10 : usually lies on the left side of the chest but can also be on the back (dorsal) surface of the animal.
Unipolar limb leads – used little Augmented leads
Bipolar Lead System
Recording +Reference –
Lead 1: left arm with respect to the right arm. Lead 2: left leg with respect to the right arm.Lead 3: left leg with respect to the left arm.
These form a triangle around the heart.
Right leg is always ground.
Einthoven’s Law: Lead 2 = Lead 1 + Lead 3
Unipolar Lead System: looks at 1 point on the body w/ respect to 0.
Chest Leads (A – Wilsons Central Terminal)o Measuring the potentials in these specific spots with
respect to 0.
Limb Leads (B – Wilson’s Unipolar Limb Leads)
Augmented Leads (C – Goldberger Augmented Unipolar Limb Leads).
Why does this particular pattern occur? P wave – QRS complex – T wave
1. P wave – is due to atria depolarization
SA node fires to the atria – creates a dipole of negative charges by SA node and positive charge by atria.
PR Interval (AKA - PQ interval)
SA Node – current goes to AV node – can’t see the AV node depolarizing specifically as the current moves.
AV Node – lasts a long time delay in the AV node current takes a long time to move through the AV node towards the bundle of His and Purkinje fibers.
2. QRS Complex – Ventricular Depolarization
Q wave: Current spread through AV node, bundle branches, and Purkinje fibers and spreads through the surrounding muscle. The first thing it spreads into is the septum – it spreads kind of strangely – it goes into the left side first then moves towards the right and upwards. #2
So the vector to represent this – positive charges move towards the head and negative charges move towards the feet.
This makes a small negative deflection (Q wave) – when the septum depolarizes.
Sometimes the Q wave is not present.
Figure. Chest Leads
Figure. Atrial Depolarization
R wave: Dealing w/ lots of tissue – spread through the ventricular muscle is first through the apex – goes a little bit towards left side of the heart. You get an increase in positive versus negative deflection – creates a big dipole. #3
S wave: The last part to depolarize in the heart is the base of the left ventricle – it is because the left ventricle is so much larger than the right ventricle. It somehow creates a depolarization. #4
Species Differences
P wave is consistent – except in large animals (horse) – you may see a p-wave that has a notch in it – this is because the atria are quite large in the heart and vectors can move in different directions.
QRS Complex – can vary – has to do with the depth of the Purkinje fibers. In humans/dogs/cats Purkinje fibers are subendocardial (just below the endocardium) – so as the current moves through the bundle branches it moves into ventricles and spreads through the muscles.
In large animals & birds the Purkinje fibers are much deeper and the current spreads explosively throughout the entire ventricle and the vectors can go in many directions and cancel each other out. This “subdues” the R wave (makes it much smaller).
Everything that depolarizes must repolarize.
J point is when the ventricles are completely depolarized.
ST segment – between S wave and T wave – is the time when the ventricles contract.
3. T wave - ventricular repolarization – so then why does the T wave deflect upwards on the graph?
What causes the +ve T-wave: the ventricular repolarization occurs in the opposite direction from the depolarization.
The heart starts repolarizing from the apex and spreads towards the septum and the base. The refractory period of the cells are shorter here – the vector that represents this is the same one that represented depolarization. This accounts for the upward T-wave.
Species Differences:
Man, Ox, Swine, Sheep – the T wave is always positive. If its negative, there is something wrong with the repolarization process.
Dog, Horse – the T wave can be negative or positive and be completely normal.
U-wave: sometimes happens in humans – not really in dogs. It represents the repolarization of M cells (mid myocardial cells).
WHATS MISSING?
Atrial repolarization – this occurs during the QRS complex (so it is masked). Although sometimes you can see it in the horse (seen as a negative deflection).
Intervals & Segments
Segments: when the tracing is iso-electric (0). In my words is the points where there are no deflections – line on the ECG tracing is flat.
PR Interval (AKA PQ interval): from beginning of the P-wave to the beginning of the QRS complex. Beginning of atrial depolarization to the beginning of ventricular depolarization – tells you how long it takes the info to get from atria into the ventricles. This can sometimes be lengthened (problematic).
PR Segment: end of atrial depolarization to beginning of ventricular depolarization.
QT Interval: simply tells you all of the activity that is occurring in the ventricle. It is the time of depolarization and repolarization of ventricle. Is problematic when lengthened.
QRS Interval: is the length of the QRS complex. Duration of ventricular depolarization.
ST Segment: end of ventricular depolarization to the beginning of ventricular repolarization. Should be isoelectric – but when there is a problem with the heart it can be changed.).
ST interval – end of ventricular depolarization to end of ventricular repolarization – is not that important.
AVR = augmented vector right (right shoulder) – right shoulder is recording electrode, other two are reference electrode.
AVL = augmented vector left (left shoulder) AVF= augment vector foot.
Vector Cardiography
Mean Electrical Axis – is the peak of the R-wave – or the largest dipole when the ventricle is depolarized. It can tell you about how the current is spread and the position of the heart in the body.
Mean Electrical Axis – main vector during depolarization (R wave).
In humans the normal axis should be between 0 and +95 degrees.
In dogs the normal axis should be between +40 to +100.
Cats have loose hearts should be from 0 to +160
Deep chested animals: means the heart is not flat against the back and can be in a different plane.
Orthogonal Leads
Where are the Leads? X-axis – Sinistrodextral plane – This would be lead I – right arm is recording electrode –
left arm is reference electrode. Y-axis – caudal cranial plane – This would be AVF lead Z-axis – dorsal ventral plane – This would be one of the chest leads V10.
In dog, monkey, cat, rat, human the mean electrical axis points towards Lead II or AVF.
In horse, ox, pig, dolphin the mean electrical axis points towards V10.
Abnormal ECG
1. Axis deviationsa. Abnormal positionb. Left axis deviation: due to left ventricle hypertrophy (left ventricle too large). c. Right axis deviation: due to right ventricle hypertrophy (right ventricle too large)
d. Left bundle branch block: causes a left axis deviation – takes longer to depolarize.
2. Voltage changesa. Increased hypertrophyb. Decreased muscle massc. Fluid in pericardial sacd. Pulmonary emphysema
3. Prolonged QRSa. Hypertrophyb. Block in left bundle branches and Purkinje fibers: takes longer for the
depolarization to spread through the heart.
4. Ischemia: lack of blood flow to the heart – may lead to death of some cardiac muscle tissue (due to lack of oxygen delivery to the heart).
a. Current of Injury: results in the elevation or depression of ST segment. i. At the J point the heart is completely depolarized – the real 0
5. Abnormal T wave – species dependent (in dogs T waves can normally be +ve or –ve).
6. Arrhythmias
Left axis deviation (LAD) is a condition wherein the mean electrical axis of ventricular contraction of the heart lies in a frontal plane direction between −30° and −90°. This is reflected by a QRS complex positive in lead I and negative in leads aVF and II. Right axis deviation occurs with the QRS axis is between +90 and +180 degrees. If the QRS is predominantly negative in lead I and positive in lead aVF, then the axis is rightward (right axis deviation).
Heart Blocks
AV blocks can be at the AV node or the bundle of His.
First degree AV block
Second degree AV block: two P-waves before the QRSo Wencheback AV block – is a lengthening in the PR interval PR interval
increases then loss of a beat.
Third degree AV block: atria beats on its own, ventricle beats on its own – completely independent.
Premature Beats
Premature atrial depolarization: when two beats are too close to each other on the ECG.
Premature ventricular depolarization: spot in the ventricle decided to throw in a beat – depolarized the ventricle.
o We see this most often in ECG labs – in the students.
Ectopic Pacemakers
Supraventricular tachycardia: there is a pacemaker in the atria (not really a problem).
Ventricular tachycardia: there is a pacemaker in the ventricle (is problematic/serious) – blood pumped poorly.
Atrial fibrillation: common In horses & large dogs because they have large hearts– can interfere with the primer pump
Ventricular fibrillation: much more serious – ventricle can’t pump blood because no synchronization of the beat – this is where you bring out the defibrillator.
In general: Fibrillation: when the syncytial nature of the heart breaks down – cells are beating on their own – results in the loss of the P-wave.
Cardiac Cycle (start of new picture book).
Pressures on the left side of the heart go up to about 120 mm Hg – in basically all species.
Ventricular volumes are the same on both sides of the heart – if not the same you get a back-up of blood in the lungs or in the circulation.
Systole: is the time of contraction of the ventricle. Atrial systole happens during the diastole of the ventricle (or you can say the heart).
Diastole: is the time of relaxation of the ventricle. Is twice (~1.6x) as long as the systole (in the resting state).
Pressure on Left-Side of the Heart
Left Atrial Pressure low pressure 0-15 mmHg Has 3 waves – A, C, V
o A-wave: When atria contracts pressure goes up. o C-wave: Is a result of ventricular contraction – forces the AV valve into the left
atria which increase the pressure in the atria.o V-wave is a build-up of blood in the atria because the AV valve is closed
Ventricular Pressure Diastole: 0 mmHg Systole: up to 120 mmHg
A-wave: At the end of diastole pressure goes up a little bit because atria blood is pushed into the ventricle
Aortic Pressure Pressure varies from 80 mmHg to 120 mmHg When aortic valve opens blood forced from ventricle into the aorta and pressure
rises and then pressure starts falling to a point where the semilunar valve closes. Dicrotic notch (AKA incisura): caused by the fact that the aorta is very elastic – when
the blood is pushed into the aorta it expands to accept the blood. When the aortic valve closes the aorta recoils allowing the pressure to go up again.
o Can appear at different points depending on where you are recording it from. If you record in the aorta itself, it is close to where the aortic valve shuts. If you record in the periphery, then the dicrotic notch can appear during the diastole of the heart.
Diastolic runoff – blood running off into systemic circulation during diastole of the heart. Pressure is dropping and will drop until aortic valve opens again allowing blood to enter the aorta.
Pressure on Right Side of the Heart.
Atrial pressure (AKA central venous pressure) can be 0 and sometimes even negative. Still has A, C, and V waves – but the peak is about 35 mmHg (low).
Right Ventricle Pressure Goes from 0 mmHg to about 25-30 mmHg Also has a dicrotic notch (occurs in the pulmonary artery where pressure is b/w about
10 mmHg to 30 mmHg – should not go down to 0) Still have the run off except blood running into pulmonary circulation instead of the
systemic circulation.
Opening and Closing of the Valves Passive process; has to do w/ pressure differences and the way the valves are
structured. AV valve closes when the pressure in the ventricle is greater than it is in the atria. AV valve opens when the pressure is greater in the atria than it is in the ventricle. Aortic valves opens when the pressure in the ventricle is greater than it is in the aorta. Aortic valve closes when the pressure in the aorta is greater than it is in the ventricle.
Emptying and Filling
Filling
Rapid inflow (first 1/3 of diastole)
AV valve is open. Semilunar (Aortic) valves closed Approx 70% of the blood is coming in from the systemic/pulmonary circulation into the
ventricles of the heart. Blood passes right through the atria and goes right into the ventricle. Remember there was a buildup blood in the atria (P-wave).
Responsible for 70% of the filling of the ventricles.
Diastasis (middle 1/3 – AKA the period of reserve) Little increase in volume Can get rid of this part of the cycle and still have pumping ability & normal blood
delivery.
Atrial Systole Atrial contracts and pumps in the other 30% of blood into the ventricle.
Atrial fibrillation – common in horses and large dogs – NO P-wave – atria not acting as a primer pump (not pumping in the extra 30% of blood). Under these circumstances the heart is still pumping 70% of the blood – can still take the horse on short rides – but you wouldn’t want this to happen in a racing horse).
Emptying
Isovolumetric Contraction AV valve closed Aortic valve closed During this time – the ventricle is contracting – blood isn’t going anywhere but the
pressure is increasing. Pressure rises in the ventricle until it gets higher than the pressure in the aorta (or the pulmonary artery on the right side of the heart).
When it is higher it opens up the semilunar (aortic) valve opens.
Ejection Blood is moving from the ventricles to the aorta and pulmonary arteries.
Protodiastole Pressure in ventricles is probably less than it is in the aorta or pulmonary artery but the
valve still isn’t closing. This is because of momentum of the blood moving out of the ventricles.
At the end of this period momentum is overcome by the drop in pressure and the aortic valve closes.
Isovolumetric Relaxation Semilunar valves close AV valves closed – so ventricle is still a closed chamber Ventricle relaxing and pressure drops in the ventricle to such a degree that its less than
the pressure in the atria (b/c no blood is actually moving because the ventricle is closed) and then the AV valve can open.
Ventricular Volume
During filling the volume goes up. No change during isometric contraction. Volume goes down No change during isometric relaxation.
EDV (End diastolic volume)– the amount of blood in the heart at the end of diastole.
ESV (End systolic volume) – the amount of blood in the heart at the end of systole.
Summary (from slides):
Ventricle Volumes Left = RightEDV – period of maximal fillingESV – period of maximal emptyingStroke Volume (SV)= EDV – ESV
Stroke Volume – volume of blood ejected with each beat of the heart.
Reserve
EDV – about 160 mL – can increase quite a bit to about 250 mL
ESV – about 80 mL – if the heart pumps harder it can pump out more blood and have less ESV – meaning it can decrease to about 10-20 mL (but the heart never pumps itself dry – always a bit left).
The SV can be a lot larger when EDV increases and ESV decreases.
Cardiac Output = Stroke volume x Heart Rate (min) Is the amount of blood leaving the heart/minute.
Species differences: pressures are generally the same but volumes vary a lot among species (large heart vs big heart).
Electrocardiogram (ECG)
P-wave is atrial depolarizationIs followed by atrial contraction
QRS complex is due to ventricular depolarizationIs followed by ventricular contraction
T-wave is ventricular repolarizationIs followed by ventricular relaxation.
Heart Sounds (Phonocardiogram)
Auscultation can usually measure the 1st and 2nd heart sounds, 3rd and 4th can be heard with special equipment.
1st and 2nd heart sounds are from the closure of the valves – causes vibrations that can be heard)
1st – closure of the AV valves “lub” – longest/loudest sound
2nd – closure of the semilunar (aortic/pulmonary) valves “dub” – closes under higher pressures so it “snaps” closed – sounds usually of higher pitch and shorter duration. May see splitting during inspiration (1 valve closes before the other – aortic closes before the pulmonary valve – happens during inspiration – blood collected in the vessels of the lungs – less blood going into left side of the heart – so aortic valve closes sooner – more blood on right side of the heart and it closes later) This is NORMAL.
In other words: Increased blood in right ventricle (coming from venous veins) & decreased blood in left ventricle (being held in the lungs for a short period) – aortic valve closes sooner b/c heart isn’t quite as full and pulmonary valve shuts later because right side of heart is fuller.
3rd – filling of ventricles during diastole. In the first 1/3 of diastole there is a lot of filling – then it slows down & blood trickles in and creates the 3rd sound (a gurgle). Is normal in young horses and cattle with stethoscope.
4th – Atrial systole. Full ventricle that is relaxed, chordae tendinae pulled taught. A little more blood pumped in my atria and creates a gurgle noise. Normal in horses or cattle with stethoscope.
Abnormal Heart Sounds
1. Splittinga. Congestive heart failure – more blood in one of the ventricles – valve may close
at a different time (depends on which side of the heart it enlarged). b. Bundle branch blocks – carries depolarization current into left/right side. If there
is a block in the depolarization it takes longer for one of the sides to contract and may change the timing of valve closure.
2. Gallop Rhythmsa. Protodiastolic gallop accentuated 3rd sound (during diastole)b. Presystolic gallop accentuated 4th sound (occurs just before systole)c. Congestive Heart Failure – may be one sided.
Bundle branch block is a condition in which there's a delay or obstruction along the pathway that electrical impulses travel to make your heart beat. The delay or blockage may occur on the pathway that sends electrical impulses to the left or the right side of the bottom chambers (ventricles) of your heart.
3. Murmurs: happens when the velocity of blood is increased & makes the flow turbulent (creates sound).
a. Valvesi. Stenosis – difficulty openingii. Doesn’t open all the way – narrow passage for air to go through and
increase velocity and turbulence. iii. Regurgitation (Insufficiency) - won’t close
1. Blood can go backwards when it shouldn’t and makes the flow turbulent.
b. Anemia – increased velocity, ejection sounds (increased velocity from ventricle into aorta/pulmonary artery).
c. Ventricular septal defects – teratology of fallot: hole b/w left and right ventricle Left ventricle has higher pressures (esp. during systole) then you get movement of blood from left to right ventricle and creates turbulence.
d. Patent ductus arteriosis – opening from aorta to pulmonary artery that does not close off at birth blood leaks from aorta to pulmonary artery at increased velocity. Can be heard during both systole and diastole b/w aortic pressure always higher than the pulmonary artery.
Autonomic Nervous System (MAKES GOOD EXAM QUESTIONS)
Controls involuntary bodily functions. Influenced by higher centers:
o Cardioregulatory centres: controls hearto Vasomotor Centre: controls blood vessels.
Pressure centre and depressor centreo Also brain stem, limbic system, hypothalamus, cerebral cortex.
Two Divisions:1. Sympathetic: Fight-Flight Mechanism2. Parasympathetic: Nurturer “rest & digest”
Anatomically different Act reciprocally but sometimes synergistically.
o Reciprocal Control Parasympathetic: slows down heart, Sympathetic: speeds up heart.
Secrete different neurohormones at nerve endings.
Reflex Arc
Higher centres do have some control over the CNS.
S ympathetic Nervous System
Small myelinated fibers. Arise from T1 (thoracic) to L2
(lumbar) Ganglionic fibers run from the
CNS to ganglionic cord. Postganglionic fibers run from the
ganglion to the organs. Motor neurons travel from the
ganglion to the skim, etc.
Adrenal medulla: starts w/ preganglionic fiber all the way to the adrenal medulla. Within the medulla are modified post-ganglionic fibers called Chromaffin Cells.
Parasympathetic Nervous System
Preganglionic fibers start at the brain stem & travel from the CNS to the ganglia close or within the organ itself.
Very short postganglionic fibers within or close to the organ.
**Very Imporatant: Vagus Nerve – goes to lung, heart, stomach, intestines, etc.
Sacral nerve goes to the gonads and the large intestine.
Neurotransmitters & Neurohormones
1. Acetylcholine Cholinergic Degradation:
o acetylcholinesterase Sympathetic:
o AcH is released from pre ganglionic fibers & post-ganglionic fiber (only @ sweat glands & piloerector muscles).
o Long sympathetic nerve fibers go to the adrenal medulla and release AcH. Parasympathetic:
o releases AcH from pre-ganglionic fibers at organs and then transmits signal to post-ganglionic fiber that also secretes AcH
2. Noradrenaline = Norepinephrine Adrenaline = Epinephrine Adrenergic (nerves that secrete noradrenaline or
receptors that respond to noradrenaline) Produced in nerve terminals (Tyrosine L-dopa
dopamine noradrenaline). Sympathetic:
o Noradrenaline is released from post-ganglionic fibers most of the time. Also released from the adrenal medulla into the blood (20% of what the medulla releases).
Adrenal Gland has extra enzyme compared to nerve terminals (N-methyltransferase) that converts noradrenalin to adrenalin (80% of what the adrenal medulla secretes).
Degradation:o Taken up by nerve endings – metabolized by monamine oxidaseo Circulating – catechol-o-methyl transferase (takes 5-10x longer than degradation by
nerve terminals)
Receptors Glycoproteins on the surface of the cell that
causes a cascade of events that lead to changes within the cell.
Cholinergic Receptors – For Acetylcholine1. Nicotinic
o Reacts with Ach and nicotine.
o Present on post-ganglionic cell bodies of both parasympathetic and sympathetic divisions.
o Also on neuromuscular junction2. Muscarinic
o Reacts with AcH and muscarine (from toxic mushrooms).o Are present on the sweatgland tissue and piloerector muscle and other tissues. o Blocked by Atropine (AKA belladona – “beautiful lady”) – causes pupils to
dialate. Often given prior to surgery – treatment for bradycardia.
Adrenergic Receptors – For Adrenalin and Noradrenalin
1. 1 Receptoro Noradrenalin > Adrenalin
2. 1 Receptoro Adrenalin > Noradrenalin
3. 2 Receptoro Adrenalin >>>> Noradrenalin
Autonomic Response Depends on: Neurotransmitter (hormone) – concentration Which tissue has what receptors. Response by cell when receptor is stimulated – what
actually happens.
Autonomic Effects on Various Organs of the Body
Sympathetic – Fight/Flight Response – want to see far, do not care about gland function, want heart to increase rate and strength of contraction, mobilize the glycogen, do not care about gut function, etc.
Parasympathetic – Rest/Digest Response – don’t care about how far you can see, copious secretion from glands (for digestion), storing glycogen.
Responses of Effector Organs to Autonomic Nerve Impulses
Parasympathetic – receptors reduce the activity of the heart.
Sympathetic - 1 Receptor is most important receptor in the heart. 1 Receptor (constriction) 2 Receptor (dialation) are important in the blood vessels.
Autonomic Innervation of the Heart
Parasympathetic Division: Vagus nerve endings at SA node & AV node. It
releases acetylcholine that binds to muscarinic receptors on the heart.
Effect on Heart:o Decreases HR = negative chronotropic
effecto Decreases conduction velocity =
negative dromotropic effect.o Decrease in Contractility (atria) =
negative inotropic effect. Only in atria because nerve
endings are concentrated here. Function:
o AcH binds to muscarinic receptor – acts through secondary messenger G-protein and activates a K+ channel and potassium permeability increases.
Resting membrane potential is further from threshold
Reduces the rate of diastolic depolarization (pacemaker potential).
Takes longer to get to threshold. Vagal Escape – if its overstimulate you can actually
stop the heart. Right vagus ends on SA node and Left vagus ends on the AV node. If you stimulate both vagus nerves you stop both the AV node and
SA node. As a result, a spot in the ventricle can take over the functioning of the heart – but the beat would be much slower.
Sympathetic Division: Innervates the most of the heart (in
atria and the ventricles). It secretes noradrenalin and interacts with 1
receptor on the heart. Adrenalin and noradrenalin released
from adrenal medulla also binds to 1
Receptor Effects on Heart:
o Increased Heart Rate = Positive chronotropic effect
o Increased Conduction Velocity = positive dromotropic effect
o Increased contractility = positive inotropic effect
Function:o Catecholamines bind 1 Receptor and
activates adenylyl cyclase which makes cAMP that cascades to cause calcium channels to open – more calcium goes into sER – allows for stronger muscle contraction when released.
o More Ca into sER – holds a lot more calcium – makes the next contraction much stronger.
o Phosphorylates inhibitor troponin I – inhibits binding of Ca to troponin C – increases the rate of relaxation - allows more beats to occur.
If you cut the vagus nerve in an animal with high parasympathetic tone the heart will actually speed up.
NE released from sympathetic nerves – stimulates beta1 receptors – increases cAMP – phosphorylation of Ca channels – more ca coming in – more release of Ca from sER (aids in contraction) – Ca take up into sER = increases strength of contraction.
CAC = Cardio-accelatory centerCIC = Cardio-inhibitory center
These centres are controlled by higher centres in the brain (hypothalamus). Afferent nerve fibers carrying sensory information can also have an influence on the CAC and CIC.
Control of the Heart
ANS has an effect on the control of the heart even though the heart can beat on its own (automaticity).
Cardiac Output – is the most important measure of cardiac function. If you have heart failure it’s the inability to control cardiac output.
Cardiac Output (ml or L/min) = Stroke Volume (ml or L) x HR (bpm)An estimate of of CO in L/min = 10% of the body weight.Eg. 5 kg cat = CO of 0.5 L/min
SV = end diastolic volume – end systolic volume
Stroke Volume – the amount of blood pumped out of the heart with each beat. When we speak of it we usually refer to the left side of the heart. BUT the SV should be the same on both sides. If it is not equal you can have back up of blood in the lungs or systemic circulation.
Cardiac Output should also be the same on both sides.
Cardiac Index (ml/min/m2): cardiac output/body surface area – is a good way of comparing animals of different sizes.
Measurement of Cardiac Output
1. Flowmeter Movement of blood through magnetic field. Flow meters put around the aorta (very invasive) – measures flow of blood coming from
the left side of the heart. Electrical potential proportional to velocity (cm/min). If you know vessel diameter you can convert it to flow.
2. Ultrasonic Techniques Non-invasive Dopple Effect – shift in pitch proportional to velocity – need to know vessel diameter to
convert to flow. Echocardiogram – pulses of sound energy, echos produce when travelling through
tissue. Records the position and movement of heart valves. It is the gold standard right know for measuring cardiac output.
Can measure EDV-ESV = SV. SV x HR = CO.
3. Fick Principle
Indirect method – used a lot in the past – can measure blood flow in the hearts and kidneys.
CO = O2 consumption / [O2] arterial – [O2] venous
4. Indicator Dilution Method Inject known quantity of indicator into venous circulation. Concentration of indicator determined in the arterial circulation (femoral) with time.
Above Graph:
5 mg injected into venous circulation. Monitor concentration of dye in arterial circulation (red line). As it comes across the dye concentration increases and then falls as recirculation occurs (doesn’t fall to 0). Get the average concentration under the curve (light red box). Also need a time: so we extrapolate the downward slope to 0 – in the top graph the time is extrapolated to 12 s. Plug it all into the equation to get CO.
Bottom graph: Dye dilution was slower than the top graph – CO much lower.
** wont be asked to do any of these calculations.
These graphs also show how fast recirculation occurs – takes about 10 seconds on the top graph. About 18 seconds on the bottom graph.
Regulation of Cardiac Output
CO = SV x HRAny alteration of SV or HR will alter CO.
1. Preload Resting tension – is stretching the muscle. Active tension – is the tension you get
when you stimulate the muscle to contract.
Skeletal muscle has: Ascending curve and descending curve: Ascending: As the muscle gets more
stretched out the amount of active tension produced increases.
Descending: If you stretch the muscle more the amount of active tension produced can decrease.
Is the amount of blood entering the heart during diastole (EDV or venous return).
When actin/myosin are too overlapped you do not get a lot of active tension. When actin/myosin are not overlapped enough you also do not get a lot of active tension.
Cardiac Muscle Length Tension Active tension has the same ascending curve but
not the same descending curve. When you stretch cardiac muscle a lot you can still stimulate a good contraction in the heart.
Titin is different in cardiac muscle (less stretchy) than the titin protein in skeletal muscle.
The resting tension applied in the heart is known as preload: depends on how full the heart is with blood.
Increased contraction with increased length (preload) due to:A. Better overlap of actin/myosin filamentsB. Increase in calcium from the sarcoplasmic reticulumC. Increases sensitivity of myofilaments to calcium.
Force Transducer Figure If we add weight (preload) the muscle stretches out and
the muscle may contract stronger. In the heart the preload is equal to the EDV (end
diastolic volume) or can be thought of as venous return.
Frank Starling Mechanism (Starlings Law of the Heart) When the heart is stretched, contractility increases –
more is pumped out o The heart responds to an increase in blood by
increasing the strength of contraction. Increased preload (VR or EDV) increases, contractility
increases, SV increases, and CO increases.
Period of filling (heart is relaxed) there is only a little bit of an increase of pressure. Happens during diastole.
Isovolumetric contraction. Period of Ejection – when aortic valve increases
and pressure drops. Isovolumetric Relaxation. The shaded in area is the work done by the
heart. It increases when there is an increased volume of blood in the heart (increases the diastolic pressure).
SV is the distance across the shaded area. If the area is increased – then the SV is also increased.
2. Afterload
Add something to stop the muscle from stretching then add a weight (afterload). In
order for the muscle to contract (shorten) it is has to pick up the weight (weight that the heart has to overcome for the heart to contract).
Examples of Increased Afterload: Increased arterial pressure : heart has to work harder to pump. Hypertrophy (increasing
muscle mass) may occur to pump the blood out of the heart. Aortic Stenosis: aortic valve stenosed (harder to get blood through) increases the
resistance that the heart must pump against. Increased afterload = decreased SV and CO.
**Preload and Afterload have opposite effects on cardiac output! **
3. Heart Rate
Increase in right atrial pressure = Increased HR = Increased CO- stretches the SA node.
Bainbridge Reflex Increased right atrial pressure – atrial receptors stimulated
o Increased sympathetic dischargeo Increases HR and contractility = Increases COo Sinus arrhythmia: increase in HR during inspiration and decrease during
expiration. During inspiration you create a –ve pressure that helps draw blood back to the heart increases pressure stretches receptors in atria. During expiration +ve pressure less venous return.
Increases sympathetic tone (chronotropic effect) = Increases CO
If HR is too high doesn’t allow time for filling (SV decreases). There is a limit to an increase in HR that has a +ve effect on CO.
4. Inotropic State
Degree of contractility of the heart (how strong is contraction) – related to sympathetic tone.
Resting – baseline sympathetic tone.
As you increase the EDV (preload) SV increases and as the preload increases it reaches steady state.
Increase in sympathetic stimulation – can get SV a lot higher – with a rise in preload. (Both increases preload and sympathetic stimulation greatly increases CO).
Increase SV = Increase CO
Hemodynamics
Complications:“blood” not just a liquid is a suspensionTubes used do not vasoconstrict/vasodialatePump used is basic – in reality heart is complex and responds to chemical/hormonal changes.
1. Velocity vs. Flow
Velocity – rate of displacement with time (cm/sec) Flow – volume displacement (ml/min)
o e.g. Cardiac output. Flow and Velocity are Related:
o Flow (ml/min) = velocity (cm/min) x area (cm2)o Velocity = flow area.
Eg. Garden Hose: put the finger over the end of the hose (decreases cross sectional area) – increases the velocity of the flow.
Capillaries have a very large cross sectional area. The velocity in them is very slow which you need for exchange of nutrients/waste etc.
Velocity and Pressure (Flow constant).
Bernoulli’s Principle: Narrowing in a tube increases velocity but
decreases pressure.
2. Flow
Flow = Pressure/Resistance (MEMORIZE).
Need a difference in pressure to get some flow. Flow is inversely proportional to resistance (blood clot, thrombis increases resistance and
decreases flow). Flow is directly proportional to a DIFFERENCE in pressure.
Flow inversely proportional to length – longer vessels = decrease in flow. Flow is directly proportional to the radius4
o Radius of 1 = 1 ml/mino Radius of 2 = 16 ml/mino Radius of 4 = 256 ml/min
This means a very small changes in diameter (via vasoconstriction/vasodialation) has a tremendous effect on flow.
Flow is inversely proportional to the viscosity of the flow. Poiseuilles Law: Flow directly proportional to Pr4/viscosity * length (remember)
3. Viscosity
Blood is thicker than water (3-4 times). Plasma is 1.5-2 times water Increased hematocrit = increased viscosity Polycythemia = increased viscosity Anemia = decreased viscosity Units dyne cm/sec2 (poise) Small vessels: Fahraeus – Lindqvist Effect
o Applies to vessels about the size of arterioles. o The red cells align themselves in the center. Close to the endothelium is a layer of
plasma. This decreases the viscosity! Capillaries:
o White cells stick to the endothelium (inflammation) = increases viscosity. o RBCs line-up & change shape to fit through channels = decreases viscosity.
4. Kinds of Flow
Laminar Flow – velocity in the centre of the vessel is faster than the liquid on the edges.
Turbulent Flow – eddy currents – can damage blood vessels (hardens the arteries). Can happen in the aorta where velocity is high.
Reynolds number = (Density x Diameter x mean velocity) / Viscosityo >200-400 turbulence in brancheso 2000-3000 turbulence in straight vessels.
We can increase turbulence by narrowing the arteries and creating small arteries. Blood seeps through at a high velocity and creates sounds that help us to indirectly measure arterial blood pressure.
5. Resistance
Resistance = Viscosity x Length/ r4
o OR R=P/F Total Peripheral Resistance (AKA Systemic Vascular Resistance): the resistance across the
systemic circulation – 9-20 mmHg/L/min – arterioles are mostly responsible for this. Pulmonary Vascular Resistance – resistance across the pulmonary circulation – 0.25-1.6
mmHg/L/min Left side of the heart – thicker walls – has to work harder – pumping into a higher
resistance. Right side of the heart – thin walls – doesn’t work as hard – pumping into a lower resistance.
6. Conductance
Conductance = 1/Resistance (inversely proportional).
Resistance in Series:RT= R1+R2+R3
Resistance in ParallelCT=C1+C2+C3 (conductance)1/RT=(1/R1 + 1/R2 +1/R3)RT= 1/=(1/R1 + 1/R2 +1/R3)
7. Distensibility
Increase diameter with an increase in pressure. Arteries are more distensible because they have more elastic tissue. Veins also have some
elastic tissue and they are distensible – but their distensibility also depends on the fact that they are very thin walled (very collapsible compared to arteries).
Law of Laplaceo Tension in wall (T) = transmural pressure (p) x radius (r)o E.g. In capillaries in the feet – a lot of pressure on these capillaries – why don’t they
burst?? The reason is the radius of the capillaries is very small – the small radius allows quite a bit of pressure before the tension in the wall builds up to an extent that causes the wall to break.
o Sometimes the body can respond to the increase in pressure by increases the thickness (ventricular hypertrophy).
8. Compliance (capacitance)
Compliance = V/P Distensibility x volume Veins are the capacitance vessels. They are distensible but not very much. They can hold a
lot of volume because there are lots of them.
Components of the Circulation
Aorta Artery --? Arteriole Precapillary Sphincter Capillary Venule Vein Vena Cava
Basics:Capillary – mostly made up of endothelium, very thinned walled. Aorta/Arteries – have lots of elastic tissues (lots of Distensibility)Arterioles/Terminal Arterioles – have lots of smooth muscle compared to everything else, can constrict/dilate. Thick walled relative to capillaries/venules.
Aorta/Large Arteries Transports blood under high pressure. Windkessel Vessels – change pulsatile to smooth flow because of their elastic tissue.
When blood comes out of left ventricle into the aorta there is a lot of elastic tissue that stretches during systole and recoil during diastole – helps the pressure to remain more stable.
Prevents pressure from becoming too high (decreases work of heart).o Afterload – if pressure it too high w/in arteriole system the heart must pump
harder against it. Prevents pressure from becoming too low (maintains coronary circulation).
o If too low coronary arteries wont fill.
Arteriole Last branches of the arteries
Sympathetic nerve endings ( receptors - vasoconstriction, 2 receptors in skeletal muscle - vasodilation)
Resistance vessels – contribute most to the total peripheral resistance
Precapillary Sphincters Control flow to capillary beds Have lots of smooth muscle to constrict – do not have a lot of ( or 2 receptors)
Capillaries Exchange fluid and gases (O2 & CO2) nutrients, wastes b/w blood and tissues – small &
permeable Low velocity
Venules Offers some resistance Effects exchange in capillaries Smooth muscle w/ receptors – sympathetic stimulation thin, collapsible
Veins takes blood back to heart holds most of the bodies blood at any given time valves for one-way flow collapsible and distensible capacitance vessel
Arteriovenous Anastomoses Goes from artery to vein w/o capillaries in between Shunt – no nutrient exchange with tissues – there is heat exchange. Occur in the skin
Total Cross Sectional Area
Velocity is inversely proportional to the total cross sectional areaVelocity = 1/cross sectional area
Area (cm2) Velocity (cm/s)Aorta 5 33-40Capillaries 5000 0.07
Capillary designed for exchange – need a big area for that to occur and blood needs to move very slowly!
Quantity of Blood
Arteries 13%Arterioles 2%Capillaries 5%Venules/Veins 46%Large Veins 18%Pulmonary Vessels 9%
Pressure and Resistance
Increase in pressure during systole. Decrease in pressure during diastole.
Diastolic pressure being high has to do with the elastic tissue & vasoconstriction. It doesn’t get extra high because of elasticity.
Mean Systemic Filling Pressure = 7 mmHgo If you stop the heart and let the pressure
equilibrate in systemic circulation is would = 7 mmHg
o Indicates how full the vasculature with blood
o Hemorrhage would lower this value. Mean Pulmonary Filling Pressure = 10 mmHg
o Indicates that pressure in pulmonary system is much more consistent. Pressure in Right Atrium is very close to 0 = central venous pressure. If you stop the heart and let the pressure equilibrate in systemic circulation is would = 7
mmHg
Total Peripheral Resistance (TPR) Systemic Vascular Resistance (SVR) Resistance across the systemic circulation. Flow = Pressure/Resistance Resistance = Pressure/Flow Arterioles (Resistance Vessels) most responsible or TPR.
o In the graph above the greatest drop in pressure is at the level of the arterioles.
Microcirculation
Arteriole has smooth muscle w/ receptors. Precapillary sphincters – smooth muscle w/ no /2 receptors. Capillaries – endothelium w/ no smooth muscleVenules have smooth muscle (not as much as arterioles w/ receptors on them).
Arterioles Venules
Systole
Diastole
Right Atrial Pressure (Central Venous Pressure)
Capillary Exchange
1. Diffusion Gases, H2O, urea, NaCl, glc, etc. Dependent on:
o Concentration gradiento Capillary permeabilityo Molecular size – limited
at MW 60,000 (radius < 3nm)
o Surface areao Lipid Solubility
Occurs mainly paracellularly (b/w the cells) but also through pores and cell membrane.
Figure – paracellular diffusion and water moving through aquaporins.
2. Filtration – Bulk Flow Depends on the tissue
o Kidney > Liver > Muscle > Brain (tight junctions in Blood Brain Barrier)o Increased during inflammation (e.g. histamine)o Site: pores, fenestrations, discontinuous endothelium
Forces Affecting Filtration
I. Hydrostatic Pressures: pressure from the fluid within the vessels
Arterial Capillary Pressure: 25 mmHg – fluid moves out of the vessel into interstitial space.
Venous Capillary Pressure: 10 mmHg – forces fluid out into interstitial space.
Interstitial pressure - (-6 mmHg) pushes into the vessels. Lymphatics always draining the interstitial pressure – so the pressure is a –ve pressure –
fluid moves from vessel into the interstitial space Without lymphatic drainage the interstitial pressure would move fluid from the
interstitial space into the vessel. Arrow shows the force going in (but the fluid is moving out).
2. Osmotic Forces
Capillary Colloid Osmotic Pressure (AKA oncotic pressure) – proteins within the capillary - helps draw fluid into the capillary – the force is about 25 mmHg.
Interstitial Colloid Osmotic Pressure – proteins within the interstitial space – draws fluid out of the capillary – force is much less than the CCOP – but still has a force of about 5 mmHg.
Starlings Law of Ultrafiltration
Fluid Movement (out of the vessel/capillary) = K [(Pc + i) – (Pi + c)]= K [Forces out of vessel - Forces into the vessel]
K – filtration coefficient (permeability & surface area)Pc – hydrostatic pressure in the capillary - interstitial colloid osmotic pressurePi - interstitial hydrostatic pressurei - capillary colloid osmotic pressure
Arterial Side: Fluid Movement = K [(25+5) – (-6+25) = K (11mmHg) = Net movement out of the capillary
Venous Side: Fluid Movement = K[(10+5) – (-6+25)=K(-4 mmHg) = Net movement into capillary
Values not equal – SOME lost in the interstitial space. Everything released from the capillary into the interstitial tissue spaces – some is lost as it is picked up by the lymphatics.
What Affects Bulk Flow
1. Changes in Hydrostatic Pressure
Increased Filtration-Increased Venous BP (eg. In RH failure – backup of fluid on venous side)-Increased Arterial BP
Decreased Filtration
-Increased Peripheral Resistance (constrict arterioles (resistance vessels) less hydrostatic pressure & less blood getting into capillaries on arterial side)-Increased Interstitial Pressure (makes it +ve instead of –ve eg. Blockage in the lymphatics).
Right Heart Failure – increased venous pressure – capillaries lose more fluid. Left Heart Failure – back up of blood & pressure in the pulmonary circulation – lose more fluid from the capillary into interstitial space fluid in the lung.
2. Changes in Colloid Osmotic Pressure
Increased Filtration
- Decreased Capillary Colloid Osmotic Pressure - Increased Interstitial Colloid Osmotic Pressure (build-up of protein in the interstitium)
3. Large Molecule MovementA. Vesicular transportB. Fenestrated endothelium – large openings in the capillary spacesC. Tissue dependent muscle > lung > brain
Albumin is a large molecule – doesn’t readily cross the endothelial barrier – SOME can travel paracellularly, SOME can go through the vesicles (create a channel), SOME goes along with the fluid, SOME attach to specific carries that take albumin across.
Lymphatics
Network of capillaries and larger vessels Main channel is the thoracic duct and right lymphatic duct: gather the lymph from the
body and empty it into the subclavian veins. Very thin-walled & collapsible
A. Transport of Fluid and Protein from interstitial spaces to the circulation: lymphatic capillary w/ loos endothelial
cells. If interstitial pressure increases, it pulls the lymphatic capillaries apart and a channel is opened and lymph can move inside.
B. Transport of other compounds – some substances transported primarily in lymph at certain locations. E.g. Fats are absorbed into and transported primarily by the lymphatics
C. Protective – transports through lymph nodes (holds a lot of the immune cells).
Volume Transported equal to the plasma volume daily (3-4L/day). ¼ - ½ of circulating plasma proteins.
What Influences Lymphatic FlowA. Increased Interstitial Pressure = Increased Lymphatic FlowB. Lymphatic Pump - larger lymphatic vessels w/ smooth muscle around them & valves
within. When the vessel is full is stretched and then it contracts forces the lymph forward. Valves in prevent backflow.
C. Increased Skeletal Muscular Activity = Increased Lymphatic Flow
Control of Blood Flow
1. Local
In capillary bed there are precapillary sphincters (where blood comes from arterioles and moves into the capillaries – help to control blood flow to the capillary). These sphincters do not have many receptors for the autonomic nervous system.
Acute Local Control – second by second, minute by minute. o Autoregulation – means the capillary bed controls themselves. o Metabolic Changes
Vasodilators – CO2, lactic acid, adenosine, K, H, prostaglandins (waste product build up).
Nutrient Lack – decreased O2
If the tissue the capillary is in is metabolizing heavily it fills up with waste products (CO2, lactic acid, adenosine, K, H, prostaglandins). These waste products can cause vasodilation of the precapillary sphincter allows more blood flow from the arteriole into the capillary & takes away the waste products. It is similarly controlled by oxygen lack lets more blood in to supply more oxygen.
In Brain CO2 is extremely important – these capillary beds would be controlled in a different way.
Eg. Reactive Hyperemia – increase in blood flow to an organ following reestablishing flow to an organ. (If you block blood flow to an organ – then let the flow back in – there Is an increase in blood flow).
Long Term Local Controlo Increase vascular growth – angiogenesis. o May occur at high altitudes (low O2 – big stimulator) – increases vascular growth
– more O2 can be held in the blood with more vessels.
2. Whole Body Regulation
Mammals are able to shift their blood from one location to another – as needed.
Neural (autonomic nervous system)o Directs blood from one body part to another. o Depends on the receptors of the ANS.
Arterioles – resistance vessels, constriction reduces blood flow to a certain area.
Adrenergic Receptors – & 2 receptors
4 cholinergic vasodilation at these sites is of questionable physiological significance. 6 sympathetic cholinergic system causes vasodilation in skeletal muscle, but this is not involved in most physiological response.
Therefore, this mean that acetylcholine is of little significance.3 dilation predominates in situ because of metabolic autoregulatory phenomena – This means that in coronary arteries dilation via 2 receptors is important but is also controlled by the autoregulatory phenomena 5 when adrenaline is released it stimulates 2 receptors & causes dilation in skeletal muscle, but vasoconstriction caused by receptors in blood vessels of other abdominal viscera
Cholinergic Receptors - In coronary arterioles receptors causes constriction & 2 receptors cause dilation.- receptors stimulated by noradrenaline & adrenaline – causes constriction of the blood vessels.
Neural Regulation Sympathetic Regulation
o Noradrenalin release acts on receptors – causes constriction Vasomotor (Pressure) Centre (in Medulla Oblongata)
o Influences the whole body Sympathetic nerves go to the arterioles and veins.
Vascular Tone: always a little bit of a release of neurotransmitters (noradrenaline)o Primarily sympathetico Increased stimulation = vasoconstrictiono Decreased stimulation = vasodilationo Is the main way the arteriole resistance is
controlled. Cholinergic receptors but only a few cholinergic
nerveso In some spp. Vasodilation can be blocked by atropine.
Seen in dog, cat, fox, sheep, monkey, goats May involve vasodilators like nitric oxide, brady kinin, histamine.
Splenic contractiono Releases more blood into circulation in response to sympathetic stimulation.
Happens during fight/flight response or during times of blood loss.
3. Hormonal
I. Adrenalin (epinephrine), noradrenalin (norepinephrine) – released from adrenal gland. receptors - vasodilation 2 receptors on smooth muscle of blood vessels in skeletal muscle – vasodilation
– primarily adrenalin interacts with these receptors. Fight or Flight Response – strong sympathetic stimulation releases both
adrenalin and noradrenalin – shifts blood from the periphery & viscera towards the skeletal muscle.
II. Angiotensin – vasoconstrictor Angiotensin I (vasoconstrictor) Angiotensin II (powerful
vasoconstrictor) ACE: can be inhibited by ACE
inhibitors – that lower blood pressure & protects the kidney – prevent conversion from Ang I Ang II.
III. Aldosterone – vasoconstrictor May have a direct effect on the blood vessels
IV. Vasopressin (AKA Antidiuretic hormone) Vasoconstrictor Released from anterior pituitary in response to osmotic changes in the body Saves water (kidney) Important in conditions of blood loss.
V. Bradykinin Vasodilator Local response – important in inflammation
VI. Histamine Vasodilator of post-capillary venules
VII. Prostaglandins Vasodilators (PGI2, PGF2a) Vasoconstrictors (PGH2)
VIII. Endothelial Derived Relaxing Factor Nitric oxide – vasodilator – released from endothelium – local response
IX. Endothelin Vasoconstrictor – local response
X. Atrial Natriuretic Factor (Peptide) Dilation of vessels and most importantly the afferent arteriole
oBringing more blood into the glomerulus Comes from the atria – released from the myocytes when stretched. Brain Natriuretic Factor – released from the ventricle – also causes BV dilation
Arterial Blood Pressure
High value – systolic blood pressure – occurs during heart contraction Low value – diastolic blood pressure – occurs during heart relaxation.
Pulse Pressure can be increased by increasing the systolic pressure or lowering the diastolic pressure.
Blood Pressure Measurement
- Want to determine the systolic or diastolic pressures.
- Listen to sounds in brachial artery or you can feel the pulse.
- Increase the pressure in the cuff to over the systolic pressure – should hear nothing in brachial artery and should feel no pulse because you stopped blood flow.
- Slowly let pressure out of cuff – it will eventually reach the same pressure as the systolic pressure and blood will start flowing with some turbulence and creates a sound (Korotkoff sounds).
- When you the cuff reaches the same pressure as the diastolic pressure the
sound should go away – blood is flowing smoothly with no turbulence.
- Systolic pressure – when you 1st hear the sounds, Diastolic pressure – when the sounds go away. The pulse method can only be used to measure the systolic pressure & NOT the diastolic pressure.
Representative Adult Arterial Blood Pressure (Species Differences)
From Horse down to the Mouse – all the blood pressures are relatively constant/similar.
Abnormal BP: Giraffe – long neck – need to keep blood flowing
to vital organs (brain – high up). Blood pressure needs to be high to make it up to the brain. If blood pressure is too high, it damages the blood vessels – giraffe has adapted to it.
High blood pressure in birds – acceleration/deceleration during flying – accelerating blood is forced away from the brain – need to increase blood pressure to make sure it gets up to the brain.
Normal Variations in Blood Pressure
Respiration – Traube Hering Waves Related to changes in respiration
Increase during expiration – decrease during inspiration Due to
1. Mechanical - Left atrial inflow decreased due to blood pooling in lung during inspiration.- During inspiration, intrathoracic pressure decreases & draws blood into right atrium
effect seen during expiration. 2. “Spill over” from the respiratory centre. Close connection of resp centers near the cardiovascular centre in the medulla.
Medulla or Baroreceptor Oscillations – Mayer Waves – lower frequency than Traube-Hering waves.
- Has to do with oscillation in the baroreceptors and their influence on the medulla.
Control of Atrial Blood Pressure
- Flow = Difference in Pressure / Resistance - Difference in Pressure = Flow x Resistance. - Difference in pressure is across the system circulation = arterial pressure - the RA
pressure (CVP)- Since right atrial pressure = 0 then Atrial Pressure = Flow x Resistance- Arterial Pressure = CO x Total Peripheral Resistance. - CO = HR x SV- Anything that influences HR, SV or TPR influences the Arterial blood pressure. - If we increase SV or HR then the amount of blood going into arterial system increases =
increase in arterial blood pressure. - If you increase the TPR then the amount of blood staying in the arterial system increase
= increase in arterial blood pressure.
I. Rapidly Acting Mechanism
Baroreceptor Reflex (WILL BE Q on EXAM)
- Found in aortic arch and in the carotid sinus (where blood pressures are high). - Rapidly responds to changes in blood pressure- Information from receptors go to the medulla via afferent fibers to the medulla.
o The ones in the arch travel up the glossopharyngeal nerveo The ones in the carotid sinus travel up the vagus nerve.
- Vagus n (efferent part) takes parasympathetic information from the brain to the heart.- Sympathetic nerve fibers go from the medulla to ganglia and then to the blood vessels.
Increase in blood pressure barorecptors stimulated goes to Cardioaccelatory Centre and Cardioinhibitory centre and the Vasomoto Centre sends out information via autonomic nervous system increase in parasympathetic tone (Increase AcH) and a decrease in sympathetic tone (decrease in noradrenaline).
In sheep – elevate the head – blood leaves the head and pools elsewhere in the body – baroreceptor reflex kicks in and increases blood pressure to get the blood up to the head.
Elevated the caudal end – blood pressure is high in the head – gotta decrease it – baroreceptor reflex kicks in & causes decreased HR, CO, BP, Contractility, SV & some vasodilation.
Carotid and Aortic Bodies - Chemoreceptors - in the same location as the baroreceptors- Respond to lower changes in pressure <80 mmHg
- Responds to decreased pC2 & pH & increased pCO2. - Information collected is brough to CAC, CIC & vasomotor centre.
Low Pressure Receptors - Do not respond to low pressures – rather they are receptors in areas of low pressure
(Right atrium, pulmonary artery). - Increased Blood pressure – stretches the right atrium or pulmonary artery – this
information goes to higher centres and induces vasodilation. o Vasodilation decreases TRP
Increases the hydrostatic pressure: increases perfusion of capillaries and decreases blood volume & thus decreases BP.
o Decreased ADH – less vasoconstriction – more fluid losso Decreased angiotensin – less vasoconstriction
Less aldosterone – less fluid retention (less sodium reabsorbed)o Release of Atrial Natriuretic Peptide (from stretch)
Dilates afferent arteriole of the kidney & helps increase urine output Increase in salt & urine output – helps to reduce the blood volume Increase heart rate (COUNTERINTUITIVE – called the Bainbridge reflex).
Increase to move the blood through the heart.
CNS Ischemia (very sever blood loss)- Blood pressure so low that blood not getting to the brain. - Responds to decrease in blood flow, increased pCO2 & lactic acid- Respond @ pressure < 50 mmHg- “Last Ditch Stand” strong sympathetic response.
o Arterioles undergo vasoconstriction to increase BP to get blood up to brain.
Hormonal Regulation- Decreased BP- Increases adrenalin & noradrenalin- Increase in vasopressin (ADH)
o Results in increase TPR & BPo Also saves water which increases BV, CO then BP.
- Renin Angiotensin Systemo Kidney releases renin converts angiotensinogen to angiotensin – increases TPR
and BPo Helps release aldosterone from adrenal cortex – increases Na/H2O reabsorption
– increase blood volume.
Capillary Fluid Shift- Increase Arterial Pressure – more hydrostatic pressure in capillaries – help to shift the
blood from the capillaries into the tissues – reduces the blood volume & thus decreases BP.
- Opposite also occurs (movement of fluid from interstitium back into capillaries).
Stress Relaxation
- Veins (capacitance vessels) distend to accommodate increased or decreased blood volume. They change in response to blood volume to prevent drastic changes in blood pressure
- Limit is 30% increase or 15% decrease.
II. Long Term Regulation (occurs over months)
It is believed that this is now a lot more complex – it is believed that some of the fast acting mechanisms may play a role in this.
This graph shows the timing of response from the mechanisms talked about above. Baroreceptors are the most fast acting!
Pulse Pressure- In order to change pulse pressure you can change the systolic or diastolic pressure- Effect on Systolic Pressure or Diastolic Pressure
Increase Pulse Pressure Increase SV, Decreased compliance/elasticity (b/c Windkessel vessels not working so well. Decrease TPR (diastolic run off happens faster)
Decrease Pulse Pressure Decreased HR (more time for heart to fill)
Pressure Pule “pulse”
- Ejection of blood into aorta sets up a pressure wave.- Travels down arterial tree
o 15x faster than blood in aortao 200x faster than blood in arteries
- Also, jugular pulse – waves reflected back from the heart to the jug vein. - Pulse described as weak, strong, bounding, rapid.
Venous Pressure
Affected by:
I. Central Venous Pressure (pressure in RA)- If decreased HR and decreased contractility – blood pools in atrium, central venous
pressure builds up (increases) and so does the venous pressure. May result in edema. - Inspiration decreases intrathoracic pressure decreases central venous pressure.
II. Blood Volume- Increase in blood volume increases mean systemic filling pressure increases
venous pressure.
III. Sympathetic Tone (in veins w/ alpha receptors). - Increase tone decreased compliance increased venous pressure.
IV. Total Peripheral Resistance- If decrease TPR (controlled by dilation of arterioles) increases venous pressure- Allows more blood to flow from arterial side to venous side.