Block 3 - Cardiovascular Flashcards
(120 cards)
1
Q
Describe the major functions of the cardiovascular system.
A
Blood transportation network.
Heart pumps blood through blood vessels.
Blood carries nutrients, oxygen and waste products to and from the cells.
2
Q
Define the 2 circulatory systems.
A
1) pulmonary circulation = between heart and lungs.
2) systemic circulation = between heart and all organs and tissues.
3
Q
Describe where the heat lies in the body.
A
The heart is found in the middle mediastinum. It sits obliquely with 2/3rd of the heart being left of the mid sternal line and the other 1/3rd to right. It sits within the pericardium.
4
Q
Describe the pericardium, including the two layers.
A
- Fluid filled sac that surrounds heart and the great vessels.
- Made up of two layers.
1) Fibrous Pericardium
Tough connective tissue
Prevents overfilling
2) Serous Pericardium
Parietal layer
Visceral layer
Allows movement
5
Q
Describe the heart wall layers.
A
1) Epicardium – outer layer
2) Myocardium – middle layer, cardiac muscle
3) Endocardium – inner layer
Between the myocardium and the endocardium is the subendocardial layer which is loose connective tissue containing small blood vessels and nerves and the branches of the impulse conducting system.
The Purkinje fibers found in the sub-endocardium distribute excitatory activity for ventricular contraction.
6
Q
Draw a diagram of the structures of the heart.
A
[see notes for answer]
7
Q
Describe atrioventricular valves during systole and diastole.
A
- Diastole occurs when heart muscles relax as it fills with blood.
- AV valves open during ventricular diastole due to relaxed papillary muscles.
- Systole occurs when heart muscles contract and blood is pumped out.
- AV valves close during systole due to contraction of papillary muscles creating tension of chordae tendinea.
8
Q
Describe semilunar valves.
A
- Pulmonary valve; between right ventricle and pulmonary trunk.
- Aortic valve; between left ventricle and aorta.
- Prevent backflow of blood into the ventricles as it has cusps in the lumen.
9
Q
Describe the conducting system of the heart.
A
- Generates and transmits impulses to produce coordinated contractions.
- Consists of sinoatrial node, atrioventricular node, atrioventricular bundle (Bundle of His), and Purkinje fibers.
1) Excitation signal is created by the sinoatrial node.
2) The wave of excitation spreads across the atria, causing them to contract.
3) Upon reaching the atrioventricular node, the signal is delayed.
4) Signal conducted into Bundle of His, down the interventricular septum.
5) The bundle of His and the Purkinje fibers spread the wave impulses along the ventricles, causing them to contract.
10
Q
Describe the arteries of the heart.
A
- Arteries supply heart with oxygenated blood.
- Left and right coronary sinus arteries emerge from aortic sinus of ascending aorta.
- Always carries blood away from the heart.
11
Q
Describe the veins of the heart.
A
- Veins drain the heart of deoxygenated blood.
- Drains into coronary sinus which then empties into the right atrium.
- Always carries blood in the direction of the heart.
12
Q
Describe the major blood vessels.
A
Arteries = carry blood from the heart and distribute it around the body. Relatively high pressure.
Veins = return blood to the heart, low pressure.
Capillaries = connect arterial and venous sides of circulation,, exchange of materials.
13
Q
Describe the 3 layers of tunic’s.
A
1) Tunica intima – single layer of cells.
2) Tunica media – smooth muscle.
3) Tunica adventitia – outer connective tissue.
Arteries and veins share the same 3 layers. Arteries have thicker walls and smaller lumen due to the higher blood pressure (tunica media is thicker). Veins contain valves to prevent backflow.
14
Q
Describe the cardiac cycle.
A
The cardiac cycle is the sequence of pressure and volume changes that takes place during cardiac activity.
The mechanical events of the cardiac cycle are brought about by rhythmic changes in cardiac cycle electrical activity.
15
Q
Describe the 2 periods of the cardiac cycle.
A
The cardiac cycle consists of alternate periods of:
- Systole (contraction and emptying)
- Diastole (relaxation and filling)
The atria and ventricles go through separate cycles of systole and diastole. Unless qualified, these terms refer to what’s happening with respect to the ventricles.
16
Q
At rest, _________ is longer in duration and it accounts for ___ of the cardiac cycle.
A
Diastole
~65%
17
Q
Describe the mechanisms of valve action.
A
When pressure is greater behind the valve, it open.
When pressure is greater in front of the valve it closes (it does not open the other way).
18
Q
Describe mid-diastole.
A
Atrial and ventricular pressures low. Ventricles contain ~80% of final filled volume. Aortic and pulmonary valves are closed. Aortic pressure is high.
19
Q
Describe late diastole.
A
P wave of ECG occurs. Towards end of P wave atria contract – increasing atrial pressure – most of the blood in the atria is propelled into ventricles – adds 20% to ventricular pressure. Volume in each ventricle at the end of diastole; ~130mL when standing, ~160mL when laying down.
20
Q
Describe end of diastole/early systole.
A
QRS complex of ECG begins – start of ventricular depolarization. Ventricles contract at end of QRS complex – early systole. Rapid increase in ventricular pressure. AV valves snap shut – first heart sound. Ventricles contract but both AV and aortic valves are shut – no blood can enter of leave. Isovolumetric or isometric phase.
21
Q
Describe the ejection period.
A
Ventricular pressure exceeds arterial pressure aortic and pulmonary valves open. Blood is ejected into the aorta and pulmonary artery. Aortic pressure rises from diastolic minimum of 80mmHg to systolic peak of 120mmHg. Corresponding pressure in the pulmonary artery are 8mmHg diastolic and 25mmHg systolic.
22
Q
Describe the end of ventricular systole.
A
T wave signals ventricular repolarisation. Ventricles start relax – ventricular pressure falls below aortic pressure – aortic valve shuts – second heart sound - and dicrotic notch (incisura) an aortic pressure record. AV valves are also shut – no blood can enter or leave. Isometric ventricular relaxation.
23
Q
Describe the filling period.
A
Ventricular pressure falls below atrial pressure. AV valves open. Major part of ventricular filling. Blood which entered atria during ventricular systole is released into ventricles by opening of AV valves. Atrial and ventricular pressures fall sharply and ventricular volume increases rapidly.
24
Q
Outline the 5 major phases of the cardiac cycle.
A
1) Passive filling during ventricular and atrial diastole
2) Atrial contraction
3) Isovolumetric ventricular contraction
4) Ventricular ejection
5) Isovolumetric ventricular relaxation
25
Describe the heart sounds.
Heart sounds are generated by heart action.
Can be detected using a phonocardiogram.
There are 2 distinct heart sounds:
The first coincides with the beginning of systole, produced by closure of the AV valves.
Second begins with the onset of diastole, closure of the aortic and pulmonary (semilunar) valves.
Abnormal sounds in pathological conditions are known as murmurs.
26
Describe the origin of electrical activity in the heart. (i.e. specialised cells)
The heart contracts rhythmically as a result of action potentials it generates itself. This property is called autorhythmicity. There are two specialised types of cardiac cell:
1) Contractile cells (99% of the heart, normally don’t initiate APs)
2) Autorhythmic cells (do not contract. They initiate or conduct APs)
27
Describe pacemaker activity.
Cardiac autorhythmic cells do not have a resting membrane potential, instead they display pacemaker activity. Pacemaker activity refers to the ability of specialized heart cells, particularly those in the sinoatrial (SA) node, to spontaneously and rhythmically generate electrical impulses that control the heart's rate and rhythm.
28
Describe pacemaker potential.
An autorhythmic cell membranes slow drift to threshold is called the pacemaker potential. Autorhythmic cells cyclically initiate APs which then spread through the heart to trigger contraction without any nervous stimulation. In cardiac physiology, the pacemaker potential is the slow, spontaneous depolarization of the cell membrane in pacemaker cells (like those in the sinoatrial node) that occurs between action potentials, eventually reaching threshold and triggering the next action potential.
29
Describe where the specialised non-contractile cells are found in the heart.
1) The sinoatrial node (SA node)
2) The atrioventricular node (AV node)
3) The bundle of His (atrioventricular bundle)
4) Purkinje fibres
The sinoatrial node is the normal pacemaker of the heart.
30
Describe the rate of action potentials in the non-contractile cells in the heart.
The cell of the heart are linked electrically. Therefore, the rate of the fastest will be the rate of all.
- SA node = 70-80 APs per minute
- AV node = 40-6- APs per minute
- Bundle of His and Purkinje fibres = 20-40 APs per minute
If the SA node fails or is faulty the AV node takes over as it has the next higher firing rate.
Atrial and ventricular myocardium = 0 APs per minute (normally). SA node discharge frequency can be altered by parasympathetic and sympathetic stimulation.
31
Draw a diagram depicting the spread of cardiac excitation.
[see notes for answer]
32
Outline the functions of the atrioventricular node.
AV node forms the only conducting pathway between the atrial muscle and the Bundle of His and hence ventricles.
AV node introduces considerable delay to spread of excitation (~ 100 ms). This allows time for blood to move from the atria to the ventricles.
AV node cell have well developed latent powers of rhythmicity and can take over pace-making if impulses from the SA node fail to reach them.
33
Describe the pacemaker activity of cardiac autorhythmic cells.
* Sodium increase by crossing funny channels and potassium decreases.
* Calcium entry via transient-type Ca2+ channels increase and sodium entry via funny channels decreases. This brings the wave to the threshold potential.
* Calcium entry via long-lasting Ca2+ channels increases and calcium entry via transient channels decreases. Causing the wave to spike.
* At the peak of the wave potassium entry increases and calcium entry via long-lasting channels decreases. Bringing the wave back under the threshold potential to start the process again.
* Step 1 and 2 combined are known as the pacemaker potential, where there is a slow depolarisation of the membrane.
34
Draw a diagram of the pacemaker activity of cardiac autorhythmic cells.
[see notes for answer]
35
Describe the phases voltage change across the cardiac myocytes.
The cycle of voltage change across the cardiac myocytes occurs in 5 distinct phases:
1) Depolarisation
2) Early repolarisation
3) Plateau phase
4) Late repolarisation
5) Resting potential
36
Draw a diagram depicting the depolarisation of the ventricular muscle.
[see notes for answer]
37
Describe the action potential in a cardiac contractile cell.
- Sodium entry causes the wave to spike rapidly from -90mV to +30mV past the threshold potential.
- Sodium entry decreases and transient potassium exit increases causing the wave to fall.
- Calcium entry via long-lasting channels increases and potassium decreases through transient and leaky channels. Causing the wave to plateau, slowing the fall of the wave.
- Calcium entry via long-lasting channels decreases and potassium entry increases via ordinary voltage-gated channels causing the wave to fall rapidly back down to -90 mV.
38
Describe the electrical activity in the heart and ECG.
Cardiac muscle fibres must contract and relax in a co-ordinated manner during the cardiac cycle.
Contraction is triggered by APs normally initiated by the SA node and conducted across the heart via a specialised conduction system.
- SA node fibres fires APs at a rest of 70-80 APs per minute at rest.
- Rate of firing is regulated by the autonomic nervous system.
Neighbouring cardiac muscle cells are linked by the presence of gap junctions. Gap junctions allow the rapid spread of APs from cell to cell, e.g. an AP originating in the SA node first spreads throughout both atria, stimulating the simultaneous contraction of R and L atrial muscle.
The ECG is a record of the overall spread of electrical activity through the heart.
Electrical currents generated by cardiac muscle are conducted through the body fluids.
A small part of this electrical activity reaches the body surface where it can be detected using recording electrodes.
The record produced is an electrocardiogram (ECG or EKG).
39
Describe the three important points when considering what an ECG represents.
1) An ECG is not a direct recording of the actual electrical activity of the heart.
2) The ECG is a complex recording representing the overall spread of activity throughout the heart during depolarisation and repolarisation. It is not a recording of a single AP in a single cell at a single point in time.
3) The recording represents comparisons in voltage detected by electrodes at two different points on the body surface, not the actual potential.
40
Describe the six limb leads.
The six limb leads
Include: l, ll, lll, aVR, aVL and aVF.
Leads l, ll, and lll are bipolar leads because two recording electrodes are used. The tracing records the difference in potential between two electrodes. The electrode placed on the right leg serves as a ground electrode and is not a recording electrode.
aVR, aVL, and aVF leads are unipolar leads. Even though two electrodes are used, only the actual potential under one electrode, the exploring, is recorded. The other electrode is set at zero potential and serves as a neutral reference points.
41
Describe the six chest leads.
The six chest leads
The six chest leads (V1 to V6) are also unipolar leads.
The exploring electrode mainly records the electrical potential of the cardiac musculature immediately beneath the electrode in six different locations surrounding the heart.
42
State the names of the leads.
Lead l = right arm and left arm.
Lead ll = right arm and left leg.
Lead lll = left arm and left leg.
aVR = right arm.
aVL = left arm.
aVF = left leg.
43
Describe how an ECG is recorded.
Recording electrodes are placed on both arms, usually at the wrists, and the left leg above the ankle. Voltage recordings are made between points that form an equilateral triangle over the thorax (Einthoven’s triangle) and any single ECG trace is a recording of the voltage difference measured between any two vertices of Einthoven’s triangle. The electrode on the right leg serves as a ground electrode and the specific arrangement of each pair of connections is called a lead.
44
Describe the 3 waveforms of a normal ECG.
The P wave, the QRS complex and the T wave.
The P wave represents atrial depolarisation.
The QRS complex represents ventricular depolarisation.
The T wave represents ventricular repolarisation.
These shifting waves of de- and repolarisation bring about alternating contraction and relaxation of the heart, respectively, the mechanical events of the heart lag slightly behind the rhythmic changes in electrical activity.
45
Describe the ECG waves.
1) No wave is recorded for SA node depolarisation.
2) In a normal ECG, no separate wave for atrial repolarisation is visible. The electrical activity associated with critical repolarisation occurs simultaneously with ventricular depolarisation and is masked by the QRS complex.
3) The P wave is smaller than the QRS complex because the atria have a much smaller muscle mass than the ventricles.
4) During the following 3 points intime, no current flow is taking place in the heart musculature, so the ECG remains the same at baseline:
a) During the AV nodal delay (PR segment)
b) When the ventricles are completely depolarised and the cardiac contractile cells are undergoing the plateau phase of their AP (ST segment).
c) When the heart muscle is completely repolarised and at rest and ventricular filling is taking place (TP interval).
46
Describe the components of the ECG waves.
P wave = atrial depolarisation.
PR segment = AV nodal delay.
QRS complex = ventricular depolarisation (atria repolarising simultaneously).
ST segment = time during which ventricles are contracting and emptying.
T wave = ventricular repolarisation.
TP interval = time during which ventricles are relaxing and filling.
P wave
Atrial depolarisation moving towards the recording electrode.
Q wave
Left to right depolarisation of the interventricular septum moving slightly away from the recording electrode.
R wave
Depolarisation of the main ventricular mass moving towards the recording electrode.
S wave
Depolarisation of ventricles at the base of the heart moving away from the recording electrode.
T wave
Ventricular repolarisation moving in a direction opposite to that of depolarisation accounts for the usually observed upward deflection.
47
Draw a diagram of the action potential in cardiac contractile cells.
[see notes for answer]
48
Draw a diagram for action potential and contractile response including the refractory period.
[see notes for answer]
49
Describe cardiac output.
Cardiac output (CO) is the volume of blood pumped by each ventricle per minute. CO is the product of heart rate (bpm) and stroke volume.
CO=HR x SV
50
Describe stroke volume.
Stroke volume is the volume of blood (mL) ejected per contraction of a particular ventricle.
SV = end diastolic volume – end systolic volume
51
How is the strength of stroke volume is graded.
The strength of cardiac muscle contraction and according SV can be graded by:
1) Varying the initial length of the cardiac muscle fibres which in turn depends upon EDV (intrinsic).
2) Varying the extent of sympathetic stimulation (extrinsic).
52
Describe the intrinsic control of stroke volume.
Increased EDV (end diastolic volume) results in increased SV. Intrinsic control of SV depends on the direct correlation between EDV and SV. Its not a simple relationship as the heart does not eject all the blood it contains. Intrinsic control depends on the length-tension relationship of cardiac muscle, which is similar to that of skeletal muscle.
53
Describe the Frank-Starling law of the heart.
Cardiac muscle fibres vary in length before contraction, this is the main determinant in the degree of diastolic filling (preload).
Increased EDV, the more the heart is stretched. The more the heart is stretched, the larger the initial cardiac fibre length before contraction. The increased length results in a greater force on the subsequent cardiac contraction and thus in a greater stroke volume.
This intrinsic relationship between EDV and SV is known as the Frank-Starling law of the heart
Put simply:
The heart normally pumps out during systole the volume of blood returned to it during diastole; increased venous return results in increased stroke volume.
54
Describe the advantages of the cardiac length-tension relationship.
The intrinsic relationship matching SV with venous return has two major advantages:
1) Equalising output between the left and right sides of the heart.
2) When a larger CO is required e.g. during exercise, venous return is increased through the action of the sympathetic nervous system. The resulting increase in EDV autonomically increase SV
Exercise also increases HR so these two factors act together to increase CO so more blood can be delivered to the exercising skeletal muscles.
55
Outline the cellular basis for the Frank-Starling relationship.
1) Greater initial length increases the sensitivity of contractile proteins in the myofibrils to Ca2+.
2) Increased initial fibre length may also increase Ca2+ release from the sarcoplasmic reticulum.
56
Describe extrinsic control of stroke volume.
Extrinsic control -> Sympathetic stimulation increases the contractility of the heart. SV is also subject to extrinsic control by sympathetic stimulation and adrenaline. Both enhance the heart’s contractility (strength of contraction at any given EDV).
o This increased contractility is due to increased Ca2+ entry triggered by noradrenaline/adrenaline.
o Increase in inward Ca2+ flux during the plateau phase of the action potential enhances the intracellular calcium store.
o Ca2+ is required for excitation-contraction coupling in cardiac muscle cells.
o Increase the rate of relaxation of cardiac muscle cells by stimulating Ca2+ pumps, take up Ca2+ from cytoplasm more rapidly, shortening systole.
Inotropic actions. (refers to the contractibility of cardiac muscle fibres).
57
Describe the workload of the heart.
High blood pressure increases the workload of the heart.
- When the ventricles contract they must generate sufficient pressure to exceed the blood pressure in the major arteries.
- This will open the semilunar valves and allow ejection of blood. The arterial blood pressure is called the afterload because it is the workload imposed on the heart after the contraction has begun.
- The heart may be able to compensate for a sustained increase in afterload by enlarging (hypertrophy). A diseased or weakened heart may not be able to compensate completely, leading to heat failure.
58
Describe why the dP/dt is a useful index of contractility.
Several approaches are used to estimate the contractile state of the myocardium. This is important e.g. for determining the severity or progress of valve dysfunction.
The simplest of these measurements is ; max dP/dt (the maximum rate of rise in pressure).
The simplest measurements of myocardial contractility use analysis of the pressure waveform during the isometric contraction phase. The advantage of being that this is independent of afterload, the aortic valve is shut (as is the atrio-ventricular valve). They provide a global assessment of myocardial contractility, not of the cellular and molecular status of the myocardium.
59
Define preload.
Preload refers to the amount of blood in the ventricles at the end of diastole (before contraction), essentially the stretch of the heart muscle fibres just before contraction.
60
Define afterload.
Afterload refers to the resistance the heart's ventricles must overcome to eject blood, essentially the force against which the heart must contract to pump blood into the aorta (left ventricle) or pulmonary artery (right ventricle).
61
State the values for different aspects of cardiac function at rest and in exercise.
[see notes for answer]
62
Draw a diagram of the changing muscle length with tension.
[see notes for answer]
63
Draw a diagram for the Frank-Starling curve.
[see notes for answer]
64
Describe the componenets of the vascular system.
- Arteries
Low resistance vessels conducting blood to the various organs in the body with little loss in pressure. Act as pressure reservoirs for maintaining blood flow between ventricular contractions.
- Arterioles (branch off of arteries)
Major sites of resistance to blood flow. Responsible for the pattern of blood flow distribution. Participate in the regulation of arterial blood pressure.
- Capillaries
Site of exchange between blood and tissues.
- Veins
Low resistance vessels for blood to flow back to the heart. Their capacity for blood is adjusted to facilitate flow.
65
Describe the features of the different blood vessels.
Arteries - several hundred, thick highly elastic walls, large radii. Passageway from heart to organs, serve as pressure reservoir.
Arterioles – half a million, highly muscular, well-innervated walls, small radii. Primary resistance controlled resistance vessels, determine distribution of cardiac output.
Capillaries – ten billion, thin walled, large total cross-sectional area. Site of exchange, determine distribution of extracellular fluid between plasma and interstitial fluid.
Veins – several hundred, thin walled, highly distensible, large radii. Passageway to heart from organs, serve as blood reservoir.
66
Describe the composition of blood vessel walls.
[see notes for answer]
67
Describe haemodynamics.
Haemodynamics: pressure, flow and resistance.
o Throughout the vascular system blood flow (F) is always from a region of higher pressure to lower pressure. The pressure exerted by a fluid is often termed hydrostatic pressure.
o Blood flows in a cone shape, this called laminar flow.
o Units of flow are volume per unit time (usually L/min or mL/min). units of the pressure difference (delta P) driving the flow are mmHg.
o To know the flow rate we need to know: the pressure difference between two points (delta P) and also the resistance (R) to flow.
o Resistance
A measure of how different it is for blood to flow between two points at any given pressure difference. In otherwards, a measure of the friction impeding flow.
68
Outline blood flow.
Blood flow through vessels depends upon the pressure gradient and vascular resistance.
F = (delta P)/R
F -> flow rate of blood through a vessel (L/min)
(delta P) -> pressure gradient (mmHg)
R = resistance of blood vessels (mmHg.min/L)
69
Describe resistance.
Resistance to blood flow depends upon 3 factors:
1) Viscosity of the blood (designated n [eta])
2) Vessel length (designated L)
3) Vessel radius (designated R)
Radius is the main determinant of resistance. A slight change in radius brings about a notable change in flow.
70
State Poiseuille's equation.
Flow rate = (pi X pressure gradient X radius^4) / (8 X viscosity X length of blood vessel)
A two-fold change in radius will produce a 16-fold change in flow.
71
Draw a diagram of how arterial pressure fluctuates.
[see notes for answer]
72
State how to find mean arterial pressure.
Mean arterial pressure = diastolic pressure + 1/3 pulse pressure
73
State how to find pulse pressure.
Pulse pressure = systolic blood pressure – diastolic blood pressure
Diastolic pressure is not 0mmHg because during diastole the arteries are not completely empty and the blood still in them exerts pressure.
74
Draw a diagram depicting the pressures throughout the systemic circulation.
[see notes for answer]
75
Describe arterioles.
Arterioles are the major resistance vessels.
* The small radius of arterioles offers considerable resistance to blood flow.
* This high arteriolar resistance causes a marked drop in mean pressure as blood flows through arterioles.
* This pressure gradients helps drive blood from the heart to the tissue capillary beds.
* Arteriolar resistance also converts pulsatile arterial pressure into non-fluctuating capillary pressure.
Arteriolar walls include a thick layer of smooth muscle that is richly innervated by nerves of the sympathetic nervous system. This smooth muscle is also sensitive to many local chemical changes and certain circulating hormones.
76
Define vasoconstriction.
Increased contraction of circular smooth muscle in the arteriolar wall, which leads to increased resistance and decreased flow through the vessel.
77
Describe vasodilation.
Decreased contraction of circular smooth muscle in the arteriolar wall, which leads to decreased resistance and increased flow through the vessel.
78
Describe vascular tone.
Arteriolar smooth muscle displays a state of partial constriction known as vascular tone. Two factors are responsible for vascular tone:
1) Myogenic activity
2) Sympathetic activity
Tonic activity makes it possible to either decrease or increase contractile activity such as vasodilation/vasoconstriction.
Any change in contractility of arteriolar smooth muscle will substantially change resistance to flow in these vessels.
79
Describe how heart rate is determined primarily by autonomic influences on the SA node.
- The heart has its own rate set by the depolarization rate of the sinoatrial (SA) node.
- The heart is innervated by both divisions of the autonomic nervous system (even if nervous stimulation is not needed to initiate contraction):
* Increased activity in the sympathetic nerves to the heart increases heart rate (Tachycardia).
* Increased activity in the parasympathetic nerves to the heart decreases heart rate (Bradycardia).
- These two divisions of the autonomic nervous system affect heart rate by changing the slope of the pacemaker potential. Changes in rate are the chronotropic effects.
- The parasympathetic nervous system (vagus nerve) releases acetylcholine (muscarinic receptor are used) while the sympathetic nervous system releases noradrenaline (acting of [beta]-1 adrenergic receptor).
- Both bring about the effects on the heart primarily by altering the activity of the cAMP 2nd messenger pathway in innervated cardiac cells.
* ACh is coupled to an inhibitory G-protein that reduces activity of the cAMP pathway.
* NorAd is coupled to a stimulatory G-protein that accelerates the cAMP pathway.
80
80
Describe the effect of parasympathetic stimulation on the SA node.
Parasympathetic NS decreases heart rate through 2 effects on pacemaker tissue.
1) Hyperpolarisation of the SA node membrane (takes longer to reach threshold).
2) Decreases the rate of spontaneous depolarisation
ACh increases K+ permeability by G protein-coupled inwardly-rectifying potassium channels (GIRKs).
81
Describe the other effects of parasympathetic stimulation on heart activity.
Parasympathetic stimulation decreases the AV node’s excitability which prolongs transmission of impulses to the ventricles.
Shortens the plateau phase of the AP in atrial contractile cells, weakening and shortening atrial contraction.
Parasympathetic stimulation has little effect on ventricular contraction.
82
Describe the effects of sympathetic stimulation on the SA node.
Sympathetic NS speeds up heart rate through its effect on pacemaker tissue (Tachycardia).
Main effect is to speed up depolarisation, so threshold is reached more rapidly.
NorAd augments If and T-type channel activity.
83
Describe the other effects of sympathetic stimulation on heart activity.
Other effects of Sympathetic stimulation on heart activity
Sympathetic stimulation of the AV node reduces AV nodal delay by increasing conduction velocity.
Speeds up spread of the AP throughout the specialised conduction pathway.
Increased contractile strength of the atrial and ventricular contractile cells (heart beat more forcefully and squeezes out more blood).
Increased Ca2+ permeability through prolonged opening of L-type Ca2+ channels.
Speeds up relaxation.
84
Describe vagal tone.
- Parasympathetic and sympathetic effects on heart rate are antagonistic.
- Heart rate is determined by the balance between inhibition of the SA node (vagus) and stimulation (sympathetic nerves).
- Under resting conditions parasympathetic discharge dominates (vagal tone; ~70 bpm to ~100 bpm).
- Heart rate can be altered by shifting the balance of autonomic stimulation.
* HR is increased by simultaneously increasing sympathetic and decreasing parasympathetic activity.
* HR is decreased by simultaneously increasing parasympathetic and decreasing sympathetic activity.
- Activity of autonomic nervous system is co-ordinated by the cardiovascular control centre, located in the brain stem.
85
Describe other factors affecting heart rate.
Autonomic innervation is the primary means by which HR is regulated.
The hormone adrenaline (epinephrine) also exerts an important influence.
Released into blood in response to sympathetic stimulation.
Adrenaline and noradrenaline increase heart rate (chronotropic action) and force of myocardial contraction (inotropic action).
Adrenaline acts on the heart in a similar manner to noradrenaline to increase HR, adrenaline reinforces the direct effect of the sympathetic nervous system.
86
Summarise parasympathetic effects on the heart.
Parasympathetic: arises in the cardioinhibitory centre of the medulla. Neurotransduction through the vagus nerve mediates inhibitory input.
Effect: acetylcholine increases SA node permeability to K+ (slow closure of K+ channels) and so increased leakage of positive charges. SA node hyperpolarises between contraction cycles resulting in fewer action potentials at SA node. Does not alter AV function. Heart rate decreases.
87
Summarise sympathetic effects on the heart.
Sympathetic: arises from the cardioaccelatory centre in the medulla. Motor neurons linking T1-T5 level of the spinal cord synapse with ganglionic neurons located in cervical 9and upper thoracic sympathetic chain ganglia. Postganglionic fibres innervate the SA and AV nodes to raise heart rate and cardiac output.
Effect: norepinephrine accelerates closure of K+ channels so reducing K+ permeability. SA and AV node membrane potential moves closer to threshold due to accumulation of positive charges in the cell between depolarisation cycles. Increases in Na+ (If) and T-type Ca2+ channel activity further accelerates depolarisation and raises frequency. Heart rate increases.
88
Describe blood pressure.
Blood pressure is the pressure blood exerts on the walls of blood vessel.
Pressure differences along the vascular tree drives blood flow in our cardiovascular system.
Because one is dependent on the other, a fall in arterial blood pressure can sufficiently reduce flow that it can be fatal. (the brain and neurons are most sensitive to blood deprivation).
89
Describe how arterial blood pressure drives flow.
Its pulsatile and is a regulated variable.
Arterial blood pressure (ABP) = cardiac output (CO) X total peripheral resistance (TPR)
90
Outline the two mechanisms that influence blood pressure.
There are two distinct mechanisms which provide influence over blood pressure.
Short term = baroreceptor reflex (neural control)
Long term = renin-angiotensin aldosterone system aka RAAS (hormonal control)
91
Describe baroreceptors.
There are two distinct mechanisms which provide influence over blood pressure.
Short term = baroreceptor reflex (neural control)
Long term = renin-angiotensin aldosterone system aka RAAS (hormonal control)
92
Describe the anatomy of baroreceptors.
Arterial blood pressure is monitored by peripheral sensors.
o Arterial baroreceptors – afferent nerve fibres which relay information to the brain about blood pressure, achieved because they are ‘ideally’ located stretch receptors. Found in:
Carotid sinus
Aortic arch
o Cardiopulmonary baroreceptors – afferent fibres of 4 types (myelinated veno-atrial mechanoreceptors, non-myelinated mechanoreceptors, coronary artery baroreceptors and chemosensors). Found in:
The heart
The pulmonary artery
Short-term control of blood pressure is achieved principally by the arterial baroreceptors.
As mean arterial blood pressure increases the firing frequency of the carotid sinus also increases.
93
Outline the process of baroreceptor activation.
1) Increase in blood pressure activates the stretch receptors in the carotid sinus.
2) Impulses are transmitted to glossopharyngeal nerve.
3) Impulses transmitted to nuclei tractus solitarii (NTS).
4) Stimulation of NTS.
5) Inhibition of SNS.
6) Vasodilation.
7) Fall in blood pressure.
Steps 4-7 are all a part of the reduction in smooth muscle contraction. This is a cyclical process which is always active.
94
Describe cardiopulmonary baroreceptors.
These are located in ‘low-pressure regions’ in the heart and vasculature.
- Right atrium = made up of many veno-atrial stretch mechanoreceptors and a couple of non-myelinated mechanoreceptors.
- Right ventricle = made up of non-myelinated mechanoreceptors.
- Pulmonary artery = made up of non-myelinated mechanoreceptors.
- Left atrium = veno-atrial stretch mechanoreceptors.
- Left ventricle = primarily made up of chemoreceptors and a few non-myelinated mechanoreceptors.
- Aorta = made up of some of the arterial baroreceptors.
95
Describe the carotid sinus baroreceptor.
Not all baroreceptors are equal
Carotid sinus baroreceptors are more sensitive.
Carotid sinus baroreceptors cause greater changes in blood pressure than aortic arch baroreceptors.
96
Describe the fibres in baroreceptors.
However both types of baroreceptors contain fibres which help deal with normal and high level blood pressure changes.
* A-fibres – deal with normal range blood pressure changes.
* C-fibres – deals with high level blood pressure changes.
97
Long term control of blood pressure.
- Relies on control of blood volume
- Controls cardiac output by Starling’s law
- Involves kidneys
98
Describe pulse pressure.
Determined by the volume of blood ejected and the compliance of arterial vasculature. Increases in volume of blood ejected by ventricles during exercise with relative compliance of vessels will cause an increase in pulse pressure.
99
Describe systolic blood pressure.
Stroke volume
- Volume of ejected from the left ventricle in mL
- Larger SV equals larger pulse pressure at any compliance
Compliance
- Aortic/arterial distensibility (afterload)
- Aorta is the most compliant vessel
- Low compliance means greater cardiac workload, an inverse relationship
100
Describe diastolic blood pressure.
Arteriolar resistance
- Total peripheral resistance (TPR)
- Modified by disease and physiology = atherosclerosis and vasoconstriction
Heart Rate
- Cardiac cycles per unit of tie, bpm
- Increased heart rate means increased DBP
101
Describe effectors altering the heart and vasculature to increase blood pressure.
o Heart
Increased sympathetic drive.
Increased noradrenaline release from the postsynaptic neurons.
Binds to [beta]1 adrenoreceptors, expressed on the myocardium.
Increased chronotropy, dromotropy, inotropy and decreased lusitropy.
Results in increased cardiac output.
o Vasculature
Increased sympathetic drive.
Increased noradrenaline release from the postsynaptic neurons.
Binds to [alpha]1 adrenoreceptors expressed on vasculature.
Results in increased total peripheral resistance.
102
Describe the effectors altering the heart and the vasculature to decrease blood pressure.
Heart
Increased parasympathetic drive.
Increased acetylcholine release from postsynaptic neurons.
Binds to muscarinic M2 receptors expressed on the myocardium.
Decreased chronotropy, dromotropy, inotropy and increased lusitropy.
Results in decreased cardiac output.
Vasculature – occurs in limited vessels
Increased parasympathetic drive.
Increased acetylcholine release from postsynaptic neurons.
Binds to muscarinic M3 receptors expressed on the vasculature.
Increased vasodilation by endothelium dependent mechanism.
Results in decreased total peripheral resistance.
103
Define chronotropy.
Chronotropy = the ability of the heart to adjust its rate in response to physical activity and metabolic demands.
104
Describe dromotropy.
Dromotropy = the effect of a substance or action on the heart’s electrical conduction system.
105
Define inotropy.
Inotropy = refers to the strength of the heart’s contraction.
106
Define lusitory.
Lusitropy = the rate at which the heart muscle relaxes during diastole.
107
Describe anaphylaxis and therapeutic vasoconstriction.
The vasculature also express [beta]2 adrenoreceptor which in physiological conditions respond to circulating adrenaline and induce vasodilation. But in those same physiological conditions the effects of noradrenaline on the [alpha]1 adrenoceptor predominates and vasoconstriction dominates.
This mechanism of blood pressure control is exploited in the management of anaphylaxis.
Anaphylaxis is a hypersensitivity reaction involving mast cell degranulation which then causes the release of vasoactive compounds, which amongst other things cause circulatory collapse due to severe hypotension.
The acute management of anaphylaxis involved administration of adrenaline to induce vasoconstriction to restore blood pressure.
108
Describe long term control of blood pressure.
Long-term control of blood pressure – hormonal control
Blood is comprised of red blood cells and plasma, both are influenced by kidneys.
Red blood cell mass is altered by erythropoietin.
Plasma volume
- Altered by salt excretion by renin-angiotensin aldosterone system (RAAS).
- Altered by antidiuretic hormone (arginine vasopressin) released by the pituitary gland.
- Altered by atrial natriuretic peptide (ANP) released from the atria due to stretch.
109
How is the state of circulation communicated to the kidneys.
How is the state of the circulation (i.e. blood volume) communicated to the kidneys?
* Hormones
* Pressure natriueses
Hormones which control water excretion and renal salts are influenced by cardiovascular receptors and initiates hormonal control.
110
Describe the effects of RAAS.
Decreased renal perfusion pressure aka a decreases in effective circulating volume, decreased afferent arteriole stretch and increased renin.
Rise in sympathetic nervous system activity to kidneys.
Decreased NaCl concentration in the macula densa (a group of cells near the kidneys).
111
Describe angiotensin II production.
Renin is a proteolytic enzyme that converts angiotensinogen from the liver to angiotensin I which is then turned into angiotensin II by ACE (angiotensin converting enzyme) in the lungs.
Renin is produced by juxtaglomerular (JGA) next to the afferent arterioles of the kidneys.
Angiotensin II is a vasoconstrictor peptide.
Production increases after a fall in blood pressure.
Recovery of blood pressure is achieved by:
- Angiotensin II stimulating aldosterone
- Angiotensin II stimulating generalized vasoconstriction
- Angiotensin II stimulating thirst at the pituitary gland
112
Describe angiotensin II and aldosterone.
Angiotensin II stimulates aldosterone from the adrenal cortes.
Aldosterone stimulates Na+ reabsorption
Requires Na+/K+ pump insertion on basal membrane
Na+ channel on apical membrane
Stimulates osmosis, therefore contributes to maintenance of plasma volume and blood pressure.
113
Describe angiotensin II and vasoconstriction.
Angiotensin II binds to AT1 receptor (in vascular endothelium cells), receptor vascular cells.
Stimulates contraction and therefore vasoconstriction.
Contributes to changes in total peripheral resistance, thus restoring blood pressure.
114
Describe angiotensin II and the sympathetic nervous system.
Angiotensin II and sympathetic nervous system. Direct vasoconstriction via AT1 is not the only means of changing TPR.
Angiotensin II increases sympathetic outflow directly in the brain -> stimulates sympathetic nervous system action potential generation.
115
Describe renin secretion.
Hypotension
JGA cells in arterioles inhibited by stretch
Fall in blood pressure cause release
Increased renal sympathetic nervous system activity. -> stimulates renin secretion by activation of adrenergic receptor.
Fall in NaCl concentration. -> activates the cascade starting from macula densa.
116
Draw a diagram depicting angiotensin, renin and aldosterone circulation and effects.
[see notes for answer]
117
Additional hormonal factors in long term control of blood pressure.
There are additional hormonal factors at play:
Arginine vasopressin = release is influenced by reduced veno-arterial receptor traffic.
Atrial natriuretic peptide (ANP) = released in response to atrial stretch.
118
Describe angiotensin-converting enzyme inhibitor.
Angiotensin-converting enzyme inhibitor (ACEi) – inhibits ACE from producing angiotensin II therefore reducing its affects in the body. First line of treatment for hypertension in individuals with type 2 diabetes.
119
Describe angiotensin receptor blocker.
Angiotensin II receptor blocker (ARB) – blocks receptors for angiotensin II thus preventing it from affecting blood pressure. First line treatment for hypotension in people without type 2 diabetes, however it is not suitable for individuals >55 years and people of black African and African-Caribbean family origin.
