Cardiovascular Physiology Flashcards
-What do peripheral chemoreceptors sense?
Partial pressure of oxygen and carbon dioxide in your blood, along with the pH in your blood.
If there is less oxygen the receptors start firing off
What are the peripherial chemoreceptors?
Carotid and aortic bodies
Afferent information from the peripheral chemoreceptors.
Information from the carotid body is sent via the —— —– nerve to the ———- nerve to the ——- in the brain.
Information from the aortic body joins the —– nerve and goes to the —– in the brain.
Information from the carotid body is sent via the carotid sinus nerve to the glossopharyngeal nerve to the NTS in the brain.
Information from the aortic body joins the vagus nerve and goes to the NTS in the brain.
What stimulates the carotid bodies in the respiratory and cardiovascular response?
Respiratory response
respiratory rate
tidal volume
airway resistance
airway secretions
respiratory muscles
Cardiovascular response
arterial pressure
heart rate
contractility
cardiac output
vascular resistance
Stimulation of carotid bodies leads to an ——– in respiration (respiratory rate and tidal volume). Cardiovascular response = ——– arterial pressure, heart rate and contractility
Stimulation of carotid bodies leads to an increase in respiration (respiratory rate and tidal volume). Cardiovascular response = increased arterial pressure, heart rate and contractility
Carotid body response
The carotid bodies sit at the base of the —— and monitor —- —— and the amount of ——– in the blood going to the ——-. When it senses the —– is receiving less ——– it gets activated as a reflex arc, you increase ———- to try and get more ——— in, if its not enough you also increase ———- drive to your kidney and peripheral ———-, so those arteries ———- to ——– total peripheral resistance (TPR), which ——– mean arterial pressure and redirects blood flow going to the ——–.
So the carotid bodies are trying to ——- the intake of ——- as well as insure there is —– flow going up to your —– that has a high —– content.
The carotid bodies sit at the base of the brain and monitor blood pressure and the amount of oxygen in the blood going to the brain. When it senses the brain is receiving less oxygen it gets activated as a reflex arc, you increase breathing to try and get more oxygen in, if its not enough you also increase sympathetic drive to your kidney and peripheral vasculature, so those arteries vasoconstrict to increase total peripheral resistance (TPR), which increases mean arterial pressure and redirects blood flow going to the brain.
So the carotid bodies are trying to increase the intake of oxygen as well as insure there is blood flow going up to your brain that has a high oxygen content.
The aortic bodies
The aortic bodies sit at the origin at the ——- arch and the activation ———- the fusion of the heart (they are guarding the fusion of the heart)
The aortic bodies sit at the origin at the aortic arch and the activation increases the fusion of the heart (they are guarding the fusion of the heart)
If your chemoreflex is blunted because the —— content is ——- you can’t increase ——– and —— — enough to get enough ——- to the carotid body and brain
If your chemoreflex is blunted because the oxygen content is low you can’t increase respiration and blood pressure enough to get enough oxygen to the carotid body and brain
Do carotid bodies have a role in hypertension?
Yes - they might
Respiratory arrest
There is an increased effort to ——- followed by loss of ——. If delivery of —— continues to be absent, death will follow.
There is an increased effort to breath followed by loss of consciousness. If delivery of oxygen continues to be absent, death will follow.
As you hold your breath and no more ——- is coming in and all of your cells are utilising the ——–, the increased drive you feel to ——- a large part of that comes from the ——— bodies as well as ——- chemoreceptors, but the ——– is dropping which is sending more signals to the —– and ——— to contract and drag oxygen in.
As you hold your breath and no more oxygen is coming in and all of your cells are utilising the oxygen, the increased drive you feel to breathe a large part of that comes from the carotid bodies as well as central chemoreceptors, but the PaO2 is dropping which is sending more signals to the brain and diaphragm to contract and drag oxygen in.
What happens to your heart rate and blood pressure when you dive?
Heart rate decreases - bradycardia
Blood pressure - usually maintained or even elevated despite the increase in HR
What is the bradycardia response during dive most driven by? How was this proved?
Driven by increased parasympathetic/vagal activity.
Atropine blocks vagal/parasympathetic (increase=decrease HR) drive to the heart. The HR doesn’t diminish as much when the subject has atropine.
Holding your breath/ Voluntary apnea
There is ——— inhibition of respiratory muscles. There is a decrease in Pa— and an increase in Pa—– which is sensed by ———–. There is a small increase in ———- activity so —- —–decreases and an increase in ———- activity causing ——- in specific areas. This means the —— —– —– doesn’t change much.
There is increased inhibition of respiratory muscles. There is a decrease in PaO2 and an increase in PaCO2 which is sensed by chemoreceptors. There is a small increase in parasympathetic activity so heart rate decreases and an increase in sympathetic activity causing vasoconstriction in specific areas. This means the mean arterial pressure doesn’t change much.
Facial immersion in cold water
There is ——— inhibition of respiratory muscles. There is a decrease in Pa— and an increase in Pa—– which is sensed by ———–. There is a small increase in ———- activity so —- —–decreases and an increase in ———- activity causing ——- in specific areas. This means the —— —– —– doesn’t change much.
You activate certain receptors near your —– and —- which causes a big increase in ——– and ——— activity. The large increase in parasympathetic activity decreases —– —– and —- —-. The large increase in sympathetic activity causes ———– which causes an increase ——– —– —- and therefore an ——— in mean arterial pressure.
There is increased inhibition of respiratory muscles. There is a decrease in PaO2 and an increase in PaCO2 which is sensed by chemoreceptors. There is a small increase in parasympathetic activity so heart rate decreases and an increase in sympathetic activity causing vasoconstriction in specific areas. This means the mean arterial pressure doesn’t change much.
You activate certain receptors near your nose and cheeks which causes a big increase in parasympathetic and sympathetic activity. The large increase in parasympathetic activity decreases heart rate and cardiac output. The large increase in sympathetic activity causes vasoconstriction which causes an increase total peripheral resistance and therefore an increase in mean arterial pressure.
Breathing with a snorkel in cold water
In this case you don’t have ——– so there is —— inhibition of respiratory muscles and you don’t have the drive from the ———— because you are ——— through the snorkel.
You activate certain receptors near your —– and —- which causes a big increase in ——– and ——— activity. The large increase in parasympathetic activity decreases —– —– and —- —-. The large increase in sympathetic activity causes ———– which causes an increase ——– —– —- and therefore an ——— in mean arterial pressure.
In this case you don’t have apnea so there is no inhibition of respiratory muscles and you don’t have the drive from the chemoreceptors because you are breathing through the snorkel.
You activate certain receptors near your nose and cheeks which causes a big increase in parasympathetic and sympathetic activity. The large increase in parasympathetic activity decreases heart rate and cardiac output. The large increase in sympathetic activity causes vasoconstriction which causes an increase total peripheral resistance and therefore an increase in mean arterial pressure
What is arrhythmia?
When the heart doesn’t work at 100% efficiency.
What is trachycardia?
Heart is working faster than it should be so it gets less efficient because there isn’t enough time for the blood to fill up.
The heart pumps blood by a continuing cycle of ——– and ———-(SYSTOLE & DIASTOLE). In order for muscle to contract, it must first be ——— activated.
The heart pumps blood by a continuing cycle of contraction and relaxation (SYSTOLE & DIASTOLE). In order for muscle to contract, it must first be electrically activated.
The heart is not activated all at one instant. Its activated by a wave of ——– that spreads throughout the ——-in a co-ordinated manner. Therefore ——— each area at the appropriate ——–,
so that ——- is effective in ——– the blood forward into the circulation.
If this pattern of spread of electrical activation is upset then the heart will not act as an effective pump with results ranging from relatively minor such as limiting exercise capacity (eg. atrial fibrillation) to fatal (eg. ventricular fibrillation).
The heart is not activated all at one instant. Its activated by a wave of excitation that spreads throughout the myocardium in a co-ordinated manner. Therefore stimulating each area at the appropriate time,
so that systole is effective in propelling the blood forward into the circulation.
What are the myocyte electrical properties?
Excitability
Conductivity
Automaticity
Excitability - Fast response AP
—— response cells are found throughout the ——-, are the most ———- action potential that is seen, are part of the contracting/working cardiac muscle in the —— and ——–, the fast part of specialized conduction system
These specialised cells are very important at coordinating this rapid spread of —— activity throughout the ——- and ensure the ——– is tightly coordinated
This is a fast response action potential because the ———– (phase —) is very fast (same speed as nerve).
Fast response cells are found throughout the heart, are the most common action potential that is seen, are part of the contracting/working cardiac muscle in the atria and ventricle, the fast part of specialized conduction system
These specialised cells are very important at coordinating this rapid spread of electrical activity throughout the ventricles and ensure the contraction is tightly coordinated
This is a fast response action potential because the depolarization (phase 0) is very fast (same speed as nerve).
Fast response AP and ionic currents.
Phase 0: upstroke (rapid —— to —-mV from resting —-mV) very rapid increase in ——- permeability.
This occurs because the membrane potential is ——– externally which is usually due to a ——– passing through it by a neighboring —-.
The cell reaches a ——– potential and at this point it’s enough to trigger the opening of voltage gated —— channels which allows the rapid influx positively charged ——— ions
The ——– channels open and close very fast
Phase 1: early ———- (to near —- mV)
——– channels start closing (stopping influx of ——-) and chloride channels start opening (transcend outwards current - largely —-) brings the cell potential back a little bit
These channels close ——- as well
Phase 2: ——— i) slow inward ——- current (i—) ii) outward —— current (i—-)
Not much change in the membrane potential - the movement of ions is almost perfectly in ——– (doesn’t mean that the ions are not moving)
There is an inwards——— current (——— is needed to make the ——– contract not —-)
Outward ——- current opposes the inward current
Phase 3: ———–
——- and —— dependent channel is switched – by the initial ———- (phase –) but it takes time for the channel to actually —–
The ——– current is the ——- current which starts to —— the cell down towards the —— membrane potential
Phase 4: resting i— high ——- conductance defines ——- Potential
As the membrane potential —– more ——- channels (i—) will open and these are ——- sensitive and the i—- channels will begin to close.
At rest there is only one type of channel open the i— channels
Background activity
——— ——— - outward current
——— —— exchanger (3 — in for 1 —- out, net positive charge)
—— ——– ——— - (3 —out for 2 — in, maintains – gradient)
Fast response AP and ionic currents.
Phase 0: upstroke (rapid depolarization to +40mV from resting -70mV) very rapid increase in sodium permeability.
This occurs because the membrane potential is depolarized externally which is usually due to a depolarization passing through it by a neighboring cell.
The cell reaches a threshold potential and at this point it’s enough to trigger the opening of voltage gated sodium channels which allows the rapid influx positively charged sodium ions
The sodium channels open and close very fast
Phase 1: early repolarization (to near 0 mV)
Sodium channels start closing (stopping influx of sodium) and chloride channels start opening (transcend outwards current - largely chloride) brings the cell potential back a little bit
These channels close gradually as well
Phase 2: plateau i) slow inward calcium current (iCa) ii) outward potassium current (iK)
Not much change in the membrane potential - the movement of ions is almost perfectly in balance (doesn’t mean that the ions are not moving)
There is an inwards calcium current (calcium is needed to make the muscle contract not sodium)
Outward potassium current opposes the inward current
Phase 3: repolarization
Sodium and potassium dependent channel is switched – by the initial depolarization (phase 0) but it takes time for the channel to actually close.
The calcium current is the repolarizing current which starts to bring the cell down towards the resting membrane potential
Phase 4: resting inward high potassium conductance defines resting Potential
As the membrane potential hyperpolarizes more potassium channels (iK) will open and these are voltage sensitive and the iNa channels will begin to close.
At rest there is only one type of channel open the iK channels
Background activity
Potassium efflux - outward current
Sodium-potassium exchanger (3 Na+ in for 1 K+ out, net positive charge)
Sodium-calcium exchanger - (3 Na+ out for 2 Ca2+ in, maintains electrochemical gradient)
Slow response AP phases
Found in the ——- and ——- nodes.
The resting potential of the cells is —— than the fast response cells at about —-mV.
The upstroke (phase –) is —– because there is — current in these cells. It is produced by an influx of ———- via i—.
Phase 2 is a slight —–.
There are either no ——– channels, or there are inactive ——– channels. This is because the cells resting potential is ——, the —– channels become active by the rapid ———– so some of the channels that need to be turned on by the —— are not ———.
Slow response AP phases
Found in the SA and AV nodes.
The resting potential of the cells is higher than the fast response cells at about -60mV.
The upstroke (phase 0) is slow because there is no current in these cells. It is produced by an influx of calcium ions via iCa.
Phase 2 is a slight plateau.
There are either no sodium channels, or there are inactive sodium channels. This is because the cell’s resting potential is high, the sodium channels become active by the rapid depolarization so some of the channels that need to be turned on by the depolarization are not activated.
Ischemia and AP
Sometimes in ischemia (part of the heart that’s not getting any blood) you have cells that become sick and the —— potentials of the —– response cells can ——- resulting in a change in action potential with a —— upstroke and —— conduction. This can lead to ——
Sometimes in ischemia (part of the heart that’s not getting any blood) you have cells that become sick and the resting potentials of the slow response cells can depolarize resulting in a change in action potential with a slow upstroke and slow conduction. This can lead to arrhythmias.
Cardiac AP - Excitability
In the —– —— period all the cells in the heart within this time period after ——– with an action potential are not able to be ——– again. This is because the ——- channels responsible for the ——— have certain properties which mean that after they have —— they cant —— again after a certain —— delay has gone by, so they can’t be —— during this period. Therefore if you hit the heart with another —— stimulation in the —— ——- period you would get —- response.
In the —- —– period you can ——— the cells but its ——- to do so you might need to inject more ——- to ——- the cells so that they are likely to be able to produce a ——-. This is because some of the —— channels have opened but others are still closed.
You get a normal action potential after the —– —– time.
Refractoriness over long periods prevents ——– of the heart
In the absolute refractory period all the cells in the heart within this time period after depolarization with an action potential are not able to be stimulated again. This is because the ion channels responsible for the depolarization have certain properties which mean that after they have opened they can’t reopen again after a certain refractory delay has gone by, so they can’t be activated during this period. Therefore if you hit the heart with another electrical stimulation in the absolute refractory period you would get no response.
In the relative refractory period you can stimulate the cells but its difficult to do so you might need to inject more current to depolarize the cells so that they are likely to be able to produce a response. This is because some of the ion channels have opened but others are still closed.
You get a normal action potential after the refractory time.
Refractoriness over long periods prevents fibrillation of the heart
Conductivity
Cardiac muscle cells do not contract in response to a ——- signal. They are ———.
The signal begins within the heart itself in the —– node.
——– activation spreads throughout ——— from cell to cell.
This occurs because each cell is electrically coupled to several other cells via ——- ——, so as one cell ———-, current spreads to ——— cells allowing coordinated ——-.
Cardiac muscle cells do not contract in response to a nervous signal. They are myogenic.
The signal begins within the heart itself in the SA node.
Electrical activation spreads throughout myocardium from cell to cell.
This occurs because each cell is electrically coupled to several other cells via gap junctions, so as one cell depolarizes, current spreads to neighboring cells allowing coordinated contraction.
Automaticity
Ability of cells to initiate an —- impulse through their own ——- activity, or diastolic ——– (AP)
These cells are found in the —— node in the ——. Some are found around the —– node and the __ ___-___ network
These cells are found in the SA node in the heart. Some are found around the AV node and the atrioventricular (AV) node network.
Pacemaker AP phases (automaticity)
The ——— membrane potential is never flat because there is a —– rate of —– in membrane potential which is responsible for the spontaneous firing.
The ———- of these cells is either due to the influx of —– via i—- or ——–.
The ——— current is slightly out doing the ——– current such that the balance of the net current movement is in favour of ——— resulting in the slow ——– membrane potential.
The outward current is due to ———- via i—- and i—- channels which are on most of the time but it varies in strength throughout the action potential.
The inward current is due to i— channels that switches on and then off and the i— current that is largely a —— current that is activated by hyperpolarization.
Pacemaker AP phases (automaticity)
The resting membrane potential is never flat because there is a gradual rate of change in membrane potential which is responsible for the spontaneous firing.
The depolarization of these cells is either due to the influx of sodium ions via iNa or calcium.
The calcium current is slightly outdoing the potassium current such that the balance of the net current movement is in favor of depolarization resulting in the slow diastolic membrane potential.
The outward current is due to potassium efflux via iK and iK1 channels which are on most of the time but vary in strength throughout the action potential.
The inward current is due to iCa channels that switch on and then off and the iNa current that is largely a funny current that is activated by hyperpolarization.
Mechanisms for altering the intrinsic rate of pacemaker discharge to increase HR;
Alter rate of ——— by ——- inward current (open the i— more) or ——- outward current (close i—- channels)
Alter ——— potential - —— to increase HR
Alter maximum ——- potential resulting in a decreased ——- membrane potential (opening i— channels more)
Mechanisms for altering the intrinsic rate of pacemaker discharge to increase HR;
Alter rate of depolarization by increasing inward current (open the iNa more) or decreasing outward current (close iK channels)
Alter threshold potential - depolarize to increase HR
Alter maximum diastolic potential resulting in a decreased resting membrane potential (opening iCa channels more)
Regulation of heart rate
HR is regulated primarily by the ——— ———- System.
——- —— —— slows heart rate, by the release of —— at ——– endings in the heart.
At the ——- node ——— increases —— permeability of cells (increase i—-). This results in a hyperpolarized and ———- pacemaker slope.
——- stimulation also slows ——- through the —– node.
Very strong ——– stimulation can stop the —— node or block the —— node.
——– speeds heart rate by the release of ———- at — node. This ——— the slope of the pacemaker ———–.
HR is regulated primarily by the Autonomic Nervous System.
Parasympathetic Nervous System slows heart rate, by the release of acetylcholine at vagal endings in the heart.
At the SA node acetylcholine increases potassium permeability of cells (increase iK). This results in a hyperpolarized and decreased pacemaker slope.
Vagal stimulation also slows conduction through the AV node.
Very strong vagal stimulation can stop the SA node or block the AV node.
Sympathetic Nervous System speeds heart rate by the release of norepinephrine at SA node. This increases the slope of the pacemaker depolarization.
What is the normal heart rate?
60-100 bpm
What is the bradycardia heart rate?
less than 60 bpm
What is the tachycardia heart rate?
Above 100 bpm
Pathway of depolerisation
Sinoatrial node
Specialised tissue in the —- —- near the —- —- —-.
Cells are continuous with the ——- myocardial cells
Spontaneous ———— at —-bpm at rest
Atria
Activation spreads through the muscle cells via —— junctions.
Atrioventricular node
—— conduction velocity —— contraction between the —— and ——— allowing the —– to top up the ——- with blood before they contract.
Bundle of His (AV bundle)
—- node and AV bundle is the only path between the —– and ——– due to the ——- —– blocking the depolerisation wave.
Bundle branches
—– bundle splits into right and left branches
Purkinje fibres
Bundle branches split into the purkinje fibre network which spreads across the ——— surface. The conduction speed is ——-.
Ventricular myocardium
Activation spreads through the muscle cells via —- junctions
Pathway of depolarization
Sinoatrial node
Specialized tissue in the right atrium near the superior vena cava.
Cells are continuous with the surrounding myocardial cells
Spontaneous depolarization at 60-100 bpm at rest
Atria
Activation spreads through the muscle cells via gap junctions.
Atrioventricular node
Slows conduction velocity delaying contraction between the atria and ventricles allowing the ventricles to top up the atria with blood before they contract.
Bundle of His (AV bundle)
AV node and AV bundle is the only path between the atria and ventricles due to the fibrous skeleton blocking the depolarization wave.
Bundle branches
AV bundle splits into right and left branches
Purkinje fibers
Bundle branches split into the Purkinje fiber network which spreads across the ventricular surface. The conduction speed is rapid.
Ventricular myocardium
Activation spreads through the muscle cells via gap junctions
Wolff-Parkinson-White Syndrome (or Pre-excitation)
People with this condition have extra conductive tissue linking the — and the ——.
When the —- node fires the activation comes down the normal pathway through the —— node and also the pathway with the extra atria-ventricle pathway resulting in part of the ——– contracting earlier.
Wolff-Parkinson-White Syndrome (or Pre-excitation)
People with this condition have extra conductive tissue linking the atria and the ventricles.
When the SA node fires the activation comes down the normal pathway through the AV node and also the pathway with the extra atrioventricular pathway resulting in part of the ventricles contracting earlier.
The electrocardiogram (ECG) visualizes the ——– activity spreading through the ——. It’s the sum of the ——— activity of the heart = VOLTAGE / TIME recording. It is recorded by ——— at different sites on the body that are connected to the —–, and are able to measure a ——– difference between different sites on the body caused by the electrical activity of the heart. This electrical activity can be recorded at a site distant from the heart because the body tissues act as ———. The heart is not the only source of electrical activity in the body, e.g. skeletal muscle
The electrocardiogram (ECG) visualizes the electrical activity spreading through the heart.. It’s the sum of the electrical activity of the heart = VOLTAGE / TIME recording. It is recorded by electrodes at different sites on the body that are connected to the skin, and are able to measure a potential difference between different sites on the body caused by the electrical activity of the heart. This electrical activity can be recorded at a site distant from the heart because the body tissues act as conductors. The heart is not the only source of electrical activity in the body, e.g. skeletal muscle
Because of the ——– conducting network the different groups of cells along the ——– are ———– very close together and the depolarization stacks up to give the ——- complex
Because of the purkinje/fast conducting network the different groups of cells along the ventricle are depolarizing very close together and the depolarization stacks up to give the QRS complex
What is a dipole?
A pair of equal but opposite charges separated by a small distance
If there is a bigger potential difference between the 2 electrodes, there will be more —– and change in ——- measured.
If there is a bigger potential difference between the 2 electrodes, there will be more current and change in voltage measured.
When electrodes are placed at ——- distances the fields become ———, changing the size of the —- and measured ——–.
When electrodes are placed at greater distances the fields become weaker, changing the size of the dipole and measured voltage.
What factors does the measured potential depend on?
Magnitude of charges (dipole)
Orientation of dipole & electrodes
Distance between dipole and electrodes
What factors does the measured potential depend on?
Magnitude of charges (dipole)
Orientation of dipole & electrodes
Distance between dipole ad electrodes
Wave front dipole - propagating wave
The resting potential of non active tissue inside is ——-, in cardiac tissue about —– and outside is ——–.
As the wave of activation spreads, the cells ——- and you get ——– rushing into the cells making the membrane potential ——–, therefore the extracellular space becomes relatively more ———-.
ECG is measuring from the —– of the body, so what we see is measured from the —– fluid
ECG recording is designed so that we get a +ve deflection when +ve pole faces the +ve electrode.
The resting potential of non active tissue inside is negative, in cardiac tissue about -80 and outside is positive.
As the wave of activation spreads, the cells depolerize and you get sodium rushing into the cells making the membrane potential positive, therefore the extracellular space becomes relatively more negative.
ECG is measuring from the outside of the body, so what we see is measured from the extracellular fluid
ECG recording is designed so that we get a +ve deflection when +ve pole faces the +ve electrode.
A bipolar system measures the difference in potential between —- electrodes. Potentials are recorded between combinations of –,– and –
A bipolar system measures the difference in potential between 2 electrodes. Potentials are recorded between combinations of RA, LA and LL.
What are the 3 standard bipolar limb leads?
Lead l = LA-RA
Lead ll = LL-RA
Lead lll = LL-LA
At any instant during the cardiac cycle: Lead – + Lead—– = Lead —-
Lead l + Lead lll = Lead ll
A unipolar system measures potential of —– electrode relative to some constant reference.
To use unipolar leads we need to form a —— lead.
All —– electrodes are connected together into one end of the ——– called the wilson’s central terminal. This can be the ——- lead. The combination of the —- electrodes during the cardiac cycle gives a constant voltage of —V as the volts —– each other out.
We have another electrode which is the ——– electrode. If the ——- is facing the —— electrode a ——– deflection is recorded.
One end of the electrode (negative) is in the centre of the chest and can be paired up with VR, VL or VF
A unipolar system measures potential of 1 electrode relative to some constant reference.
To use unipolar leads we need to form a reference lead.
All 3 electrodes are connected together into one end of the voltmeter called the wilson’s central terminal. This can be the reference lead. The combination of the 3 electrodes during the cardiac cycle gives a constant voltage of 0V as the volts cancel each other out.
We have another electrode which is the exploring electrode. If the dipole is facing the exploring electrode a positive deflection is recorded.
One end of the electrode (negative) is in the centre of the chest and can be paired up with VR, VL or VF
What set of leads are used to measure the electrical activity in the horizontal plane?
Unipolar chest leads V1-V6
How is the cardiac vector seen by leads l, ll and lll.
Lead 1&3 - see a smaller projection than the actual dipole
Lead 2 - closer to the orientation of the dipole so bigger projection
Sarcomere length tension relationship
The —— force that can be generated by skeletal muscle is proportional to the ——– length. The normal operating zone is between 1.8-2.2μm. This is when the maximum — heads are binding to the —- fibres. It’s seen on the graph as a ——- phase. ——- tension only increases when the sarcomeres are at long lengths.
The ——– myocytes operate over a much ——– zone of the sarcomere length than —— muscle, which is due to their ——— - there is much stronger ——– tissue that’s much more restrictive
The ——– stiffness of cardiac muscle limits ———.
The —— myocytes have length dependent activation. This means that the force generated by the cardiac myocyte at different lengths is not just driven by the __-___ interaction. Its also driven by ——-. The cardiac myocyte changes how it deals with the release of ——— at different lengths. This means a smaller change in ——– can give a greater force in cardiac vs skeletal muscle
As length increases there is an ———- sensitivity to ———, so as the myocyte gets ————you get a ———- contractile response for the same input of ———-.
Increased Ca2+ sensitivity of Troponin - C at greater sarcomere lengths
Increased Ca2+entry through stretch activated channels at greater SL
The active force that can be generated by skeletal muscle is proportional to the sarcomere length. The normal operating zone is between 1.8-2.2μm. This is when the maximum myosin heads are binding to the actin fibres. It’s seen on the graph as a plateau phase. Passive tension only increases when the sarcomeres are at long lengths.
The cardiac myocytes operate over a much shorter zone of the sarcomere length than skeletal muscle, which is due to their structure - there is much stronger connective tissue that’s much more restrictive
The passive stiffness of cardiac muscle limits stretch.
The cardiac myocytes have length dependent activation. This means that the force generated by the cardiac myocyte at different lengths is not just driven by the myosin-actin interaction. Its also driven by calcium. The cardiac myocyte changes how it deals with the release of calcium at different lengths. This means a smaller change in calcium can give a greater force in cardiac vs skeletal muscle
As length increases there is an increased sensitivity to calcium, so as the myocyte gets longer you get a greater contractile response for the same input of calcium.
Increased Ca2+ sensitivity of Troponin - C at greater sarcomere lengths
Increased Ca2+entry through stretch activated channels at greater SL
What causes the release of calcium from the sarcoplasmic reticulum in skeletal muscle?
Depolarization - Sodium influx
What causes the release of calcium from the sarcoplasmic reticulum in cardiac muscle?
Calcium
Myocardial contraction
Action potential (triggered by ——-)
Inward ——— current through ——- channels
——- induces rapid —— release from ——— ——-.
——- binds to ____-__ and starts cycle of ——— interactions for contraction.
Action potential (triggered by -sodium)
Inward calcium current through calcium channels
calcium induces rapid calcium release from sarcoplasmic reticulum.
Calcium binds to Troponin-C and starts cycle of filament interactions for contraction.
Myocardial relaxation
Removal of ——- from cytoplasm via;
——– ——- calcium ATPase (reuptake of calcium)
—— ——- exchange out of cell (Na+ gradient)
———- Ca2+ ATPase
As the calcium concentration drops the calcium will unbind form ___-__ and the contractile proteins will relax.
Removal of calcium from cytoplasm via;
sarcoplasmic reticulum calcium ATPase (reuptake of calcium)
sodium calcium exchange out of cell (Na+ gradient)
sarcolemma Ca2+ ATPase
As the calcium concentration drops the calcium will unbind from Troponin-C and the contractile proteins will relax
Factors influencing the inotropic state of cardiac muscle:
Action Potential duration
↑ AP ——– length –> ↑ —— influx so increased —– release –> ↑ ——- state
External Ion Concentrations
↑ external —— –> ↑ —— because increased ——- –> ↑inotropic state
Lower external —— —> slows ——- —— exchange —> —– accumulates inside –> ↑ inotropic state
Heart rate
———- heart rate—> more —- entry due to more —– —> —– time for calcium —— —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the ——– have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
——- and ———- - SNA, act through beta receptors
Mainly through activation of _-____ pathways adrenergic agonist
Cause phosphorylation of —— channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate)
Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
Action Potential duration
↑ AP plateau length –> ↑ calcium influx so increased calcium release –> ↑ inotropic state
External Ion Concentrations
↑ external calcium –> ↑ influx because increased gradient –> ↑inotropic state
Lower external sodium —> slows sodium calcium exchange —> calcium accumulates inside –> ↑ inotropic state
Heart rate
increased heart rate—> more calcium entry due to more action potentials —> less time for calcium removal —-> Ca2+ accumulation –> ↑ inotropic state
Calcium removal is depended on the time that the channels have to get it out of the cells. The amount of calcium that comes in changes with rate because the number of openings of the channels changes as well with rate.
Neurotransmitters
Adrenaline and nor adrenaline - SNA, act through beta receptors
Mainly through activation of G-protein pathways adrenergic agonist
Cause phosphorylation of calcium channels making them be open for longer
Phosphorylation of phospholamban - increased rate of pump to remove calcium, so that relaxation can occur faster, decreased inotropic state
Cholinergic muscarinic agonist (PNS)
Reduction of [Ca2+]i
decreased inotropic state
Hormones and Drugs
Xanthines (eg. caffeine)
Prevents cAMP breakdown —> increased inotropic state
Cardiac Glycosides (eg. digoxin - short term, the underlying damage continues to accumulate)
Inhibit Na+/K+ pump so there is an accumulation of Na inside the cell. Diminished Na+ gradient. Slow Na+/Ca2+ exchange . Ca2+ accumulation inside cell. Increased inotropic state
Calcium channel blockers (eg. verapamil)
reduce Ca2+ entry across sarcolemma => decreased inotropic state
Ischaemia and heart failure
negative inotropic influences. They reduce the ability of the heart to generate force
stroke volume = __ -__
SV = End diastolic volume - end systolic volume
Cardiac output = __x__
CO = Heart rate x Stroke volume
Preload = —— —– —–
End diastolic volume or pressure
Preload is the degree of —- of the muscle just before ——. It determines the —— overlap (length - tension relation) and length dependent activation. As preload increase stroke volume —— and maximum potential pressure ——.
Preload is the degree of stretch of the muscle just before contraction. It determines the filament overlap (length - tension relation) and length dependent activation. As preload increases, stroke volume increases and maximum potential pressure increases.
What is Stroke Work?
Work = Pressure x Volume
Work = MAP x SV
What is inotropic state?
Influencing muscular contractility: increasing or decreasing the force of muscular contractions
High blood pressure causes death by ——- —— disease or ——–
There is a —— relationship between your risk of death and your systolic pressure - the higher your systolic pressure the ——- the risk of coronary artery disease or stroke. So the lower the BP the better it is
High blood pressure causes death by coronary artery disease or stroke
There is a linear relationship between your risk of death and your systolic pressure - the higher your systolic pressure the greater the risk of coronary artery disease or stroke. So the lower the BP the better it is
Big arteries have a high —— component and are very ——-. Therefore the —– helps to buffer the big swings in —— when the heart is —— and ——-, allowing the flow in the rest of the body to be continuous.
Arterioles - all the blood vessels that are leading up to the ——- and end ——, controlling the blood flow to the particular organs depending on its ——. The high component of —– muscle allows this to happen by regulating the —— size and thus ——-. The high ——- means that you will see a big drop in ——– in that area.
Capillaries - ——— thin wall
Venules - connect ——- to bigger ——–.
Veins ——– of the blood is stored here. High —— tissue, floppy, —— wall to lumen ratio although the wall is —- compared to arterioles, ——– muscle - can control the —— in the veins but because of the large ——– and the pressure is —– that doesn’t change the ——– much. If you squeeze a vein it will push the blood back to the heart, increasing —— but not changing ———.
Big arteries have a high elastic component and are very stretchy. Therefore the aorta helps to buffer the big swings in pressure when the heart is ejecting and relaxing, allowing the flow in the rest of the body to be continuous.
Arterioles - all the blood vessels that are leading up to the capillaries and end organs, controlling the blood flow to the particular organs depending on its need. The high component of smooth muscle allows this to happen by regulating the lumen size and thus resistance. The high resistance means that you will see a big drop in pressure in that area.
Capillaries - endothelium thin wall
Venules - connect capillaries to bigger veins.
Veins - most of the blood is stored here. High elastic tissue, floppy, thin wall to lumen ratio although the wall is thick compared to arterioles, smooth muscle - can control the resistance in the veins but because of the large capacity and the pressure is low that doesn’t change the pressure much. If you squeeze a vein it will push the blood back to the heart, increasing preload but not changing pressure.
Capacitance
A measure of the —– to —— relationship over the entire P/V curve. Reflects the storage capacity of the vessels.
Capacitance = Change in ——/change in ——-
Veins = capacitance vessels - they can store large amounts of blood volume with little change in ——. When they —— large quantities of blood are transferred to the heart thereby increasing ——- —–.
About —- of your blood volume is held in the veins and — is held in the arteries. (ratio = 3:1)
Capacitance
A measure of the volume to pressure relationship over the entire P/V curve. Reflects the storage capacity of the vessels.
Capacitance = Change in volume/change in pressure
Veins = capacitance vessels - they can store large amounts of blood volume with little change in pressure. When the constrict large quantities of blood are transferred to the heart thereby increasing cardiac output.
About ⅔ of your blood volume is held in the veins and ⅓ is held in the arteries. (ratio = 3:1)
Compliance
The ability to hold —- at a certain —–.
Initially the relationship in veins is very —— so they are very compliant. When they are about 300 times their initial volume then the ——– starts to rise and the compliance starts to ——–.
Arteries are more linear across the whole range of pressures. They are ——-, dont have the —— and don’t ——– the same as the veins.
As a result they have ——— compliance, so their ability to —- their volume is not as good as a vein at their working pressure
Compliance doesn’t effect the MAP
The ability to hold volume at a certain pressure.
Initially the relationship in veins is very steep so they are very compliant. When they are about 300 times their initial volume then the pressure starts to rise and the compliance starts to decrease.
Arteries are more linear across the whole range of pressures. They are stiffer, dont have the elastin and don’t collapse the same as the veins.
As a result they have decreased compliance, so their ability to increase their volume is not as good as a vein at their working pressure
Compliance doesn’t effect the MAP
What are the values of normal mean arterial BP, systolic BP (max) and diastolic BP (minimum)?
MAP = 100 mmHg
systolic = 120 mmHG
diastolic = 90 mmHg
MAP=__+ __(__-__)
MAP= Pd+ 1/3 (Ps - Pd)
Pulse pressure = (__-__)
PP= Ps-Pd
Aortic compliance and pulse pressure.
During —— the aorta stretches to absorb the blood.
Blood will continue to flow in ——- due to the aorta being —— out in ——-. Therefore the ——– pressure is going to be relatively ——.
The more compliant large blood vessels are the —- the pulse pressure.
If the aorta is compliant it stretches and absorbs the volume of blood then the pressure isn’t going to be too high.
If the aorta can’t stretch and absorb the volume of blood the pressure is going to be high.
Someone with a stretchy aorta (healthy) will have a not too high systolic and diastolic pressure. Therefore will have a —- pulse pressure
Someone who doesn’t have a stretchy aorta (not healthy) will not be able to —— the volume of blood, so the —— pressure is going to be high, but because the blood is not absorbed the —— pressure is going to be lower. This means that this person will have a —– pulse pressure
During systole the aorta stretches to absorb the blood.
Blood will continue to flow in diastole due to the aorta being stretched out in systole. Therefore the diastolic pressure is going to be relatively high.
The more compliant large blood vessels are the smaller the pulse pressure.
If the aorta is compliant it stretches and absorbs the volume of blood then the pressure isn’t going to be too high.
If the aorta can’t stretch and absorb the volume of blood the pressure is going to be high.
Someone with a stretchy aorta (healthy) will have a not too high systolic and diastolic pressure. Therefore will have a small pulse pressure
Someone who doesn’t have a stretchy aorta (not healthy) will not be able to absorb the volume of blood, so the systolic pressure is going to be high, but because the blood is not absorbed the diastolic pressure is going to be lower. This means that this person will have a high pulse pressure
Pulse pressure —— with age due to ——- compliance.
As a result of a decrease in compliance systolic pressure ——— and diastolic pressure may ——–.
A less compliant aorta will result in a —– pulse pressure.
Pulse pressure increases with age due to decreased compliance.
As a result of a decrease in compliance systolic pressure increases and diastolic pressure may decrease.
A less compliant aorta will result in a larger pulse pressure
Increasing stroke volume delivered to the aorta increases arterial pulse pressure.
Systolic pressure increases in exercise because the stroke volume has increased.
The more volume that comes out the higher the pressure will be.
Has the compliance changed?
No
Diastolic pressure is determind by the ability of blood to flow ——–. This in turn is dependent on —— —- —— and — ——.
Slow heart rate = ——- diastole = blood pressure continues to —- for longer = diastolic pressure ——-
High resistance downstream = ——– for blood to flow forward = ——- diastolic pressure
During exercise the ——– pressure increases due to increased ——- ——-. The —– pressure decreases because the ——– decreases to allow more blood flow to the organs. This is why sometimes the mean pressure doesn’t change much during exercise.
If its cold then the diastolic pressure goes up during exercise
Diastolic pressure is determind by the ability of blood to flow forward. This in turn is dependent on total peripheral resistance and heart rate.
Slow heart rate = longer diastole = blood pressure continues to decrease for longer = diastolic pressure decreases
High resistance downstream = harder for blood to flow forward = increased diastolic pressure
During exercise the systolic pressure increases due to increased stroke volume. The diastolic pressure decreases because the resistance decreases to allow more blood flow to the organs. This is why sometimes the mean pressure doesn’t change much during exercise.
If its cold then the diastolic pressure goes up during exercise
Q
Arterial pressure regulation
Different mechanisms dominate in blood pressure control over different time scales.
Short term - nerual reflexes such as baroreceptors, chemoreceptors and the CNS ischemic response.
Minutes to hours - hormonal (Angi ll) and fluid shifts
Hours to days - blood volume regulation via renal mechanisms.
Can you control blood pressure without baroreceptors?
Yes
Arterial baroreceptor reflex
The carotid baroreceptors are in the ——– ——- with their nerve endings locating in the ———–. They sense ——– in the arteries. The —– ——- nerve goes into the ———— nerve up to the—— in the brain
The receptors respond to ——– changes not ——— changes. ———– changes can result in the baroreceptors moving to the new mean pressure.
If the arteries can’t —— then even if the pressure increases the baroreceptors can’t fire.
Increase in arterial pressure results in an ——– in baroreceptor firing due to increased ———. This causes an ——– in PNS which decreases —— —–, therefore decreases —- —-and a ——— in SNS due to the —— inhibiting the —— which results in decreased —- and ——–. There is decreased —– —— and decreased vascular ——— resulting in a ——– arterial pressure.
Arterial baroreceptor reflex
The carotid baroreceptors are in the carotid sinus with their nerve endings locating in the adventitia. They sense stretch in the arteries. The carotid sinus nerve goes into the glossopharyngeal nerve up to the NTS (nucleus tractus soltarius) in the brain
The receptors respond to sudden changes not gradual changes. Gradual changes can result in the baroreceptors moving to the new mean pressure.
If the arteries can’t stretch then even if the pressure increases the baroreceptors can’t fire.
Increase in arterial pressure results in an increase in baroreceptor firing due to increased stretch. This causes an increase in PNS which decreases HR, therefore decrease CO and a decrease in SNS due to the CVLM inhibiting the RVLM which results in decreased HR and vasodilation. There is decreased cardiac output and decreased vascular resistance resulting in a decreased arterial pressure.
What is the equation for blood flow?
Blood flow (Q) = change in pressure (P) / resistance (R)
Blood flow to tissues is controlled in relation to tissue ——.
Needs
When talking about the whole body blood flow = —– —–
cardiac output
To increase blood flow increase the —— of the blood vessel, or ————.
To increase blood flow increase width of blood vessel, or vasodilate
Blood flow determines —— —- and —— —–
Blood flow determines heart rate and stroke volume
Pressure
Change in pressure = ___ x _____
MAP = —- x —-
Anything that increases , —- —, —— —– or ——– will increase pressure
Change in pressure = —— usually in theory because —– pressure is minimal so it can be ignored.
If cardiac output increases during exercise resistance decreases to maintain the same mean arterial pressure
Pressure
Change in pressure = blood flow x Resistance
MAP = CO x TPR
Anything that increases , blood flow, cardiac output or resistance will increase pressure
Change in pressure = MAP usually in theory because venous pressure is minimal so it can be ignored.
If cardiac output increases during exercise resistance decreases to maintain the same mean arterial pressure
Resistance in series
Rtotal = R1 + R2+ R3…
Resistance in series:
1/Rtotal = 1/R1 + 1/R2 + 1/R3…
Approx relative resistances
RA = 20
Ra = 50
Rc = 20
Rv = 6
RV = 4
Mean velocity equation
Q = v x A
Jean Poiseuille flow
as radius increases, the flow increases and pressure decreases
Resistance to blood flow
Resistance is proportional to: The tube length (L)
The viscosity of fluid (n)
and inversely proportional to
the radius raised to the fourth power.
Determinants of blood viscosity
Temperature - gets thicker as it gets colder
Haematocrit - as Hct rises so does viscosity
Shear rate (velocity) - viscosity increases as cells aggregate
Vessel diameter - in very small blood vessels there is an apparent decrease in viscosity
Assumptions of Poiseuilles equation
steady laminar flow
rigid straight tube
Newtonian fluid
Changing pressure in BV
Increasing pressure:
Distension of blood vessel
Reduced resistance
Increased blood flow
Decreasing pressure
Reduced stretch of vessels
Increased resistance
Decreased blood flow
What is CCP
Critical closing pressure - the internal pressure at which a blood vessel collapses and closes completely
Endothelium and shear stress
As flow increases, shear stress increases causing:
NO release and vasodilation
potentially damaging endothelium
Factors resulting in turbulence
High fluid densities
Large tube diameter
High flow velocities
Low fluid viscosities
Reynolds number
Helps predict fluid flow patterns. An increase in diameter, increase in velocity or decrease in viscosity will lead to increase in Re. Turbulent flow exceeds 2000 of Reynold number
Change in pressure =
P = CO x R
Driving pressure
The pressure gradient between two points. The driving pressure governs blood flow
Transmural Pressure
The pressure across the vessel wall
Hydrostatic Pressure
Dependent on gravity
Transmural equation
P = Pi - Po
Laplace Equation
T = (P*r)/wall thickness
Hypertension contributions
ANG II, VGF, endothelin, oxidative stress increases wall tension and cause remodelling to thicker, stiffer walls with smaller lumen
Aneurysm
Thinning of vessel wall
Radius increases
Wall tension increases
Bursts!
Describe the effect of gravity on blood pressure
Blood pressure drops as height increases
Sympathetic activity on vascular resistance
NE released from sympathetic terminals binds to a1-adrenoceptors leading to vasoconstriction.
Vasodilation
Occurs in response to epinephrine released from adrenal medulla which activates B2-adrenergic receptors
A1-adrenoceptors
Linked to G-protein receptors that activate smooth muscle contraction through IP3 pathway.
B2-adrenoceptors
Act via cAMP to inhibit myosin light chain kinase, inhibiting contraction.
Salbutamol is an agonist and used for asthma
Factors promoting dilation
Decreased O2
Increased CO2 and H+
Lactic acid
Adenosine, prostaglandins and nitric oxide (NO) from endothelial cells
Rising K+ and H+ in interstitial fluid
Histamine
Elevated temps
Reactive hyperaemia
Blood flow is restored after a brief occlusion above pre-occlusion levels for a period and is driven by metabolites
Vaping
Leads to impaired vascular function
Myogenic autoregulation
Ca2+ influx by stretch channels leads to depolarisation. If pressure increases, vessel constricts normalizing flow.
Blood pressure control in exercise
Exercise increases sympathetic activity and decreases parasympathetic activity, increasing HR, CO, contractility and blood pressure.
Coupling factors
Preload and afterload are in part dependent on vascular function = coupling factors
Cardiac output equations
CO = SV x HR
CO = change in P / TPR
Cardiac output curve
Plateau determined by heart strength (contractility x HR)
Cardiac output is dependent on venous return (preload)
Determinants of venous return
Dependent on pressure gradient (Pa - Pv) and vascular resistance
Venous return = (Pa-Pv)/R
Pv = right atrial pressure and is dependent on degree of filling (blood volume and venous capacitance)
Normal values for Pa and Pv
Pa = 100
Pv = 0
Normal value for Cardiac output
6L/min
What happens to Pa and Pv if CO = 0
Pa drops to 0 and Pv will go up to equalize at 7mmHg
Systemic filling pressure
Pressure gradient is dependent on cardiac output. Increasing cardiac output will increase arterial and reduce right atrial pressure
Mean systemic filling pressure (MSF)
Pressure in the system when cardiac output = 0
MSF usually about 7mmHg
Vascular function curve (Venous Return)
- As right atrial pressure increase venous return decreases (due to pressure gradient)
- Venous return = 0 once right atrial pressure = mean systemic filling pressure
- The plateau is caused by large vein collapsing as they enter the chest if the pressure is lower than atmospheric
- Usual right atrial pressure is 0-2mmHg, resulting in a venous return of about 5L/min
Blood volume and MSFP
5000mL - 7mmHg MSFP
4000mL - 0 mmHg MSFP
MSFP and venous compliance (sympathetic tone)
Increasing blood volume of increasing sympathetic stimulation dramatically increases MSFP
Effect of filling pressure on venous return
change in P = Change in V / C
At any given right atrial pressure, as MSFP increases, venous return increases
Increased blood volume = increased PSF
Decreased capacitance (increased venous tone) = PSF
Vascular resistance and filling pressure
Increased SNA leads to increased vascular resistance and increased venous tone, increasing PSF
Cardiac function curve
Increased sympathetic stimulation results in increased CO at any filling pressure due to increase in inotropy and HR
Guyton Analysis
At steady state: CO = Venous return
e.g Blood tranfusion
Increase in mean systemic filling pressure = increase in venous return = increase cardiac output at higher RA pressure
Venous return factors
Increased venous tone (increased filling pressure)
Increased resistance (decreasing slope on CO against PRa)
Lying to standing
Immediately on standing venous return is decreased due to venous pooling. Sympathetic stimulation increases it
Exercise
Sympathetic stimulation - increased MSFP as a result of decreased capacitance. Decrease in systemic resistance and increased ventilation and muscle pumps assist venous return
Cycle of heart failure
Myocardial injury -> decreased ventricular performacne -> decreased cardiac output -> increased sympathetic activity -> Vasoconstriction, Na & h20 retention -> increased demand on the heart -> myocardial injury
Treating heart failure
Diuretics - reduce venous pressure (RAP), reduce oedema - but will reduce output
ACE inhibitors/ARB - vasodilation, reduces remodelling, reduce blood volume
Beta blockers - reduce energy demand by reducing cardiac function (also reduces chance of arrhythmias)
Relation with HR and SNA
Similar
As HR drops, SNA drops
as HR increases, SNA increases
Sympathetic pathway neurotransmitter and receptor
Norepinephrine and Adrenergic receptor
Parasympathetic pathway neurotransmitter and receptor
Acetylcholine and muscarinic receptor
Parasympathetic and sympathetic fibres
p = short
S = long
Varicosity
Vesicle containing neurotransmitter and mitochondrion
Nucleus tractus solitarius
Receive input from baro and chemo receptors
Rostro-ventro-lateral medulla
Origin of all sympathetic output
Heart rate and respiration before exercise
Increases before the onset of exercise
Blood pressure after ischemic stroke
Increases
Post-stroke hypertension is driven by the sympathetic nervous system
Consequences of high blood pressure after stroke
Haemorrhage
Oedema
Arrhythmias
Reperfusion injury
