Cardiac Physiology Flashcards
(125 cards)
1
Q
What are the main functions of the cardiovascular system?
A
Supply of oxygen and nutrients. Removal of CO2 and waste Regulation of pH of extracellular fluid Regulation of osmotic balance Signalling
2
Q
Give examples of cardiovascular disease.
A
Heart attack
Angina
Heart failure
Arrhythmias
3
Q
Describe the pump action of the heart.
A
Left and right heart acts as two pumps in series.
Output of the left and right heart is equal.
Left heart pumps blood into the body (systemic) tissue at high pressure.
Right heart pumps blood into the lungs (pulmonary circulation) at a relatively low pressure.
4
Q
How do valves contribute to the cardiovascular system?
A
Ensure unidirectional flow. If the pressure beyond the valve is greater than before it - the valve closes to prevent backward flow.
5
Q
Describe the way in which blood is pumped out from the ventricle through a valve.
A
Ventricular muscle contracts.
Ventricular pressure rises.
If ventricular pressure is smaller or equal to the pressure beyond the valve, the valve remains closed.
As soon as the ventricular pressure exceeds the pressure beyond the valve, the valve opens.
6
Q
Describe stages of blood flow through the heart in a heart beat.
A
Systemic blood flows into the right atrium from the superior and inferior vena cava. Right atrium contracts causing the tricuspid valve to open and blood to fill the right ventricle. The right ventricle contracts causing the opening of the pulmonary valve. Blood flows from the right ventricle into the pulmonary vein which distributes it throughout the lungs. Blood returns to the heart from pulmonary circulation via the pulmonary vein. Pulmonary blood fills the left atrium which contracts causing the mitral valve to open and blood to fill the left ventricle. As the left ventricle contracts, the aortal valve opens allowing the blood to exit the heart throug the aorta into the systemic blood flow.
7
Q
What is cardiac output?
A
Volume of blood pumped in a given time.
8
Q
What are the units of cardiac output measurements?
A
L/min
9
Q
How is cardiac output calculated?
A
Heart rate x Stroke volume
10
Q
What is the normal cardiac output and the cardiac output of an athlete in exercise??
A
5L/min
20L/min
11
Q
Using the value for normal cardiac output, calculate the normal stroke volume.
A
CO = HR x SV 5 = 72 x SV SV = 5/72 = 0.06944 ~ 0.07 = 70ml
12
Q
What is the Fick principle used for?
A
Calculating cardiac output
Calculating flux of blood through organs
13
Q
How is cardiac output measured using the Fick principle?
A
CO = VO2/(CV-CA)
Cardiac output = Rate of oxygen uptake / ([O2] in pulmonary artery - [O2] in pulmonary vein)
14
Q
Why is measurement of cardiac output using the Fick principle difficult?
A
Requires catheterisation to obtain O2 concentration readings.
15
Q
What methods, other than the Fick principle can be used to measure cardiac output?
A
Using indicators
Thermal dilution
Doppler ultrasound.
Echocardiography (ECG)
16
Q
How is flux of blood in an organ calculated?
A
J = Q(Cin-Cout)
Flow rate x (concentration of fluid input - concentration of fluid output)
17
Q
What is the Frank-Starling mechanism used for?
A
Ensures equal cardiac output from the left and right heart.
Contributes to increase in stroke volume during exercise.
18
Q
How does the Frank-Starling mechanism increase stroke volume to balance cardiac output from both ?
A
If the cardiac output of the left ventricle increases, the venous return from the body will also increase. This causes an increase in stroke volume by increasing the ventriclular stretch of the left ventricle and an increase of end diastolic volume because a greater venous return requires a greater ventricular output to maintain the increased cardiac output.
19
Q
What is the optimum sarcomere length of cardiac muscle and why?
A
1.9 micrometers. At lower lengths the actin filaments overlap, interfering with cross-bridge formation.
Higher sarcomere lengths cause increase in sensitivity of the contractile machinery
20
Q
What is cardiac contractility?
A
Peak contractile force at a given initial fibre length.
Peak systolic pressure for the given end-diastolic volume.
21
Q
What is the effect of increased contractility
A
Increased force and rate of contraction.
22
Q
How can contractility be increased?
A
Sympathetic stimulation (NA) or adrenaline. Glycoside drugs.
23
Q
How can contractility be calculated?
A
Contractility = Stroke Volume / End-diastolic volume
24
Q
Why does increased central venous pressure increase cardiac output but decrease venous return?
A
Cardiac output is increased because of the increased stroke volume caused by increased central venous pressure.
Venous return decreases because the pressure gradient between veins and capillaries decreases.
25
Describe the structure of the cardiac muscle.
Composed of intercalated disks which separate cells
| Many gap junctions enable conduction of electricity.
26
What is meant by myogenic electric activity?
Activity initiated within the muscle.
27
What effect do nerves have on the heart?
Modulate the heart beat.
28
Describe the events that occur within the heart muscle during a heart beat.
SA node initiates a pacemaker current.
Current spreads through the atrium causing atrial contraction.
Current reaches AV node where it is delayed to allow ventricular filling.
Current flows through the septum via the bundle of His.
Spreads across the purkinje fibres of the apex causing ventricular contraction.
29
What does the P-T labels on an ECG represent?
P - Atrial contraction
QRS - Ventricular contraction
T - Ventricular repolarisation
30
What is the pacemaker current caused by?
Calcium-induced depolarisation
31
Describe the changes in electrical currents during an impulse.
Normal membrane potential of the SA node is -60mV. At this potential the I(f) channels (funny channels - Hyperpolarisation-activated cyclic nucleotide-gated channels) open causing an exchange of Na/K where a net influx of Na is observed. Influx of sodium causes an increase in membrane potential of the pacemaker cell. Potential reaches a threshold of ~-45mV causing opening of T-type calcium channels. Influx of calcium causes calcium-induced calcium release from L-type channels at a membrane potential of -30mV. L-type mediated influx of calcium causes an spike in membrane potential reaching 0mV. At 0mV the potassium VGCs open causing an efflux of the positive charge carried on potassium ions. Sodium-calcium exchanger (NCX) is also activate to pump calcium back into the sarcoplasmic reticulum. Once the membrane potentials goes below -45mV, the I(f) channels reopen to balance the concentration sodium in the cell. The Na/K-ATP pump restores the potassium concentration.
32
Which of the currents during an impulse is the true pacemaker current?
The funny current. Funny (HCN) channels.
33
Describe the phases of the ventricular action potential.
Phase 0 - Rapid depolarisation due to influx of sodium.
Phase 1 - Early partial repolarisation caused by a transient efflux of potassium (I(to)).
Phase 2 - Plateau. Inward calcium current of L-type channels balances with the non-transient efflux of potassium.
Phase 3 - Repolarisation caused by continued potassium efflux
Phase 4 - Resting potential established by influx of potassium to keep the potential near potassium's E(K).
34
Describe how calcium-induced calcium release occurs.
Action potential travels over the sarcomere's surface membrane and down the T-tubules that perforate the sarcomere.
Depolarisation activates L-type calcium VGCs causing entry of calcium into the sarcomere.
Calcium activates Ryanodine receptors which are coupled to calcium channels. Activation causes efflux of calcium from the sarcoplasmic reticulum into the sarcoplasm.
35
How is calcium removed from the sarcoplasm after an action potential?
Repolarisation of the action potential causes calcium VGCs to close.
SERCA - Sarcoplasmic and Endoplasmic Reticulum Calcium ATPase - pumps calcium back into SR.
Remaining calcium is removed by an antiporter of calcium and sodium on the plasma membrane.
36
How is the heart rate controlled?
Intrinsic:
SA node pacemaker control.
Extrinsic:
Parasympathetic modulation:
The vagus nerve of the ANS innervates the SA node enforcing a vagal tone which reduces the SA node's firing rate to ~72BPM.
Sympathetic modulation by nerves:
Accelerator nerve causes an increase in heart rate during exercise.
Sympathetic modulation by adrenaline:
Adrenaline increases heart rate during the fight or flight response.
37
What is the SA node's intrinsic firing rate?
80-100BPM
38
How is Stroke Volume controlled?
Intrinsically by the Frank-Starling mechanism.
Extrinsically:
Sympathetic stimulation, both neuronal and adrenal, increases SV.
Angiotensin II increases SV
Hormonal (Corticosteroids and thyroxine) increase in SV.
39
Describe the baroreceptor reflex control of the blood pressure.
Increase in arterial pressure stimulates baroreceptors. Leads to increase in activity of afferent (sensory) nerves which innervate the medullary centre.
Medullary centres decrease sympathetic activity and increase parasympathetic activity.
This causes reduction in cardiac output and reduction in contractile tone in blood vessels which reduces the peripheral resistance of blood vessels.
The fall in CO and PR causes a decrease in blood pressure of the artery.
40
Other than the baroreceptor reflex, what other receptors/reflexes control blood pressure?
Veno-atrial receptors
Chemoreceptors
Lung-stretch receptors
Skeletal muscle mechanoreceptors
41
How do Veno-atrial receptors decrease blood pressure?
Increased atrial volume causes a response in the atrial wall which leads to increased heart rate.
The response also causes diuresis to decrease the volume of plasma.
42
How do chemoreceptors regulate heart rate?
Respond to hypoxia (lack of oxygen)
Constrict blood vessels to increase the PR
Heart rate increases because of increased respiration
43
How do lung stretch receptors mediate heart rate?
Increase heart rate by inhibiting the vagus nerve.
| Heart rate increases during each inspiration.
44
How do skeletal muscle mechanoreceptors regulate heart rate?
Inhibit vagal neurones during exercise to increase the heart rate.
45
Describe how the heart deals with exercise.
Blood flow through muscle increases in order to supply sufficient oxygen/glucose.
Pulmonary flow increases to increase oxygen uptake and CO2 excretion.
Cardiac output increases from 5 to 20L/min.
Heart rate increases from 72 to 180BPM by inhibition of vagus nerve and stimulation of accelerator nerve.
Contractility increases
Stroke volume increases from 70 to 105ml.
Diastole (ventricular filling + coronary blood flow) shortens proportionately more than systole.
46
How does the sympathetic system regulate cardiac action?
NA and adrenaline have similar effects.
| Activate the GsPCR pathway that triggers action potential firing rate and contraction via PKA
47
What is meant by a positive chronotropic effect?
Increase in heart rate.
48
What is meant by a positive ionotropic effect?
Increase in contractility of the heart.
49
How does the sympathetic system increase heart rate?
Acts on the SA node to induce pacemaker depolarisation before threshold is reached.
I(f) channels open and close slowly.
NA stimulates Beta1-adrenergic receptors to produce cAMP and activate PKA via the GsPCR pathway.
PKA phosphorylates calcium channels to increase their activity and sensitivity (reduces threshold).
cAMP acts on I(f) channels to increase their activity.
50
How does the sympathetic system increase heart contractility?
Acts on the ventricle.
PKA increases activity of potassium channels which shortens the repolarisation and hence shortens the AP.
PKA phosphorylates L-type channels and increases their activity.
Increased ventricular AP plateau and calcium influx triggers a more elaborate calcium-induced calcium release which leads to increased contractile force.
51
What effects does the sympathetic system have on cardiac action?
```
Increases heart rate
Increases contractile force
Increases speed of conduction through the AV node
Increases automaticity
Decreases cardiac efficiency.
```
52
What is meant by increased automaticity of the heart?
Non-pacemaker cells are more likely to initiate action potentials.
53
How does the sympathetic system decrease cardiac efficiency?
Oxygen consumption increases more than the work done because metabolism is switched to fatty acids by beta-adrenoceptor activation which requires more oxygen.
54
What are the effects of the parasympathetic system on the heart?
Decreased heart rate
Slow AV conduction
Decreased atrial contractility
Decreased automaticity
55
How does the parasympathetic system decrease heart rate?
Release of ACh which trigger a GiPCR pathway on a muscarinic M2 receptor.
Lower PKA activity means less phosphorylation of calcium channels.
Causes less calcium entry.
Beta/gamma subunit activates a potassium efflux channel causing longer depolarisation times because the outside has been made positive by the potassium efflux.
56
What are the 4 classes of cardiac drugs?
Autonomic drugs
Glycosides
Anti-arrhythmic drugs
Anti-anginal drugs
57
What is the function of autonomic drugs?
Block effects of the ANS (parasympathetic and sympathetic)
58
What are the 3 groups of autonomic drugs?
Beta-adrenoceptor agonists
Beta-adrenoceptor antagonists
Muscarinic receptor antagonists
59
What are the effects of Beta-adrenoceptor agonists on the cardiac system?
Increase heart rate
Increase automaticity
Increase contractile force
60
Give 3 examples of beta-adrenoceptor agonists and how they are used in treatment of cardiac disorders.
Adrenaline - Intravenous application in cardiac arrest
Isoprenaline - Generation of rhythm in heart block
Dobutamine - Increase in contractile force after cardiac surgery.
61
What are the effects of Beta blockers on the cardiac system?
Slow heart rate
Reduce automaticity
Reduce contractile force
Increase efficiency
62
Give 3 examples of beta blockers.
Propanolol
Atenolol
Alprenolol
63
What are the effects of muscarinic receptor antagonists on the cardiac system? Give an example
Prevent parasympathetic slowing of heart rate.
| e.g. Atropine
64
What is Atropine used for?
Treatment of myocardial infaction.
65
What are the effects of cardiac Glycosides on the cardiac system? Give examples.
Increase contractile force
Decrease heart rate
e.g.: Digoxin, Ouabain
66
How do cardiac glycosides increase contractile force of the heart?
Inhibit Na/K ATPase.
Causes a rise in intracellular sodium.
Chemical gradient for the efflux of calcium by Na/Ca exchanger decreases which causes a rise in intracellular calcium.
Leads to increased contractile force.
67
How do cardiac glycosides decrease the heart rate?
Increase parasympathetic activity
| Slow rate of conduction at AV node
68
What are the effects of overdose of cardiac glycosides?
Arrhythmias
69
What is the main therapeutic use for cardiac glycosides?
Heart failure associated with atrial fibrillation.
70
What are arrhythmias?
Disorders of normal cardiac rhythm.
71
What is Tachychardia?
A type of arrhythmia which causes increased heart rate.
72
What is Bradychardia?
A type of arrhythmia which causes decreased heart rate.
73
How are arrhythmias classified?
By change in heart rate and site of origin.
74
What are the possible sites of origin of arrhythmias and their respective arrhythmia type?
SA node - Sinus
AV node - Junctional
Atrium - Supraventricular
Ventricle - Ventricular
75
What are the 4 mechanisms by which arrhythmias arise?
Re-entry of an action potential.
Delayed after-depolarisations.
Abnormal pacemaker activity.
Heart block.
76
How does re-entry of an action potential cause arrhythmia?
Damaged tissue causes the unidirectionally flowing AP to avoid the region however after propagation the AP may return to site of origin via the damaged tissue. The arrhythmia occurs only if AP propagation is longer than the refractory period.
77
How do delayed after-depolarisations cause arrhythmia?
Damaged tissue may retain increased levels of intracellular calcium.
More calcium can be pumped out by the NCX which leads to increased intracellular sodium.
Increases the tissue's automaticity.
Ectopic beats may form inbetween regular beats due to increased sensitivity to depolarisation.
78
How does abnormal pacemaker activity cause arrhythmia?
Quescent regions of the heart begin pacemaking.
| Triggered by catecholamine-activated beta-adrenoceptors which causes increased automaticity.
79
How does heart block cause arrhythmia?
Damage to nodes causes improper conduction of AP.
80
What are the effects of complete AV node block?
Atria and ventricles beat independently.
| Ventricular rate is slower.
81
What are the effects of partial AV node blocks?
Only some SA impulses trigger contraction of ventricles.
82
What are the classes of anti arrhythmic drugs?
Class I - Sodium channel blockers
Class II - Beta blockers
Class III - Potassium channel blockers
Class IV - Calcium channel blockers
83
What is the effect of Class I anti arrhythmic drugs?
Decrease excitability of quiescent tissue.
84
What are the subclasses of Class I anti arrhythmic drugs? Give examples.
Class Ib - Lignocaine
| Class Ic - Flecainide
85
What is the difference in action of Ib and Ic anti arrhythmics?
Ib are fast binding whereas Ic bind more slowly.
86
What is the effect of Class II anti arrhythmics?
Block sympathetic effects:
Slow down heart rate
Decrease automaticity
Increase AV delay
87
How are Class II and Class II anti arrhythmic drugs used therapeutically?
Prevention of ventricular arrhythmias after MI
Reduction of stress-induced tachycardias
Prevention of supraventricular tachycardias
88
What is the effect of Class II anti arrhythmics?
Prolong the action potential and refractory period by blocking potassium channels to prevent ectopic APs
89
Name 2 Class III anti arrhytmics.
Amiodarone
| Sotalol
90
What is the effect of Class IV anti arrhythmics?
Block calcium channels.
Causes calcium entry to drop to the minimum required for an AP.
Supress ectopic beats caused by delayed after-depolarisations.
91
Name 2 class IV anti arrhythmics.
Verapamil
| Diltiazem
92
What other agents may be used to treat arrhythmias? Give examples of use.
Adrenaline - Cardiac arrest
Isoprenaline - Heart block
Atropine - Sinus bradychardia
Adenosine - Supraventricular tachycardia
93
How is acute arrhythmia treated?
Defibrillation
| Artificial pacing
94
What is angina?
Cardiac ischaemia caused by inadequate coronary blood flow.
95
What is coronary blood flow?
Blood flow to the cardiac muscle.
96
How is coronary blood flow controlled?
```
Local vasodilator signals:
Adenosine
Decreased ppO2
Decreased pH
Increased potassium concentration
```
97
How does the response of coronary blood flow to increased cardiac work take place?
Increased cardiac work leads to vasodilation in small arteries/arterioles which increases coronary blood flow.
98
How efficient is coronary blood flow?
Uses 11% of resting oxygen consumption but receives only 4% of resting blood flow.
Oxygen distribution is efficient.
99
When does coronary blood flow occur and why?
Diastole (ventricular filling).
| Ventricular pressure greater that in the aorta during systole - blood can't perfuse ventricular muscle.
100
Why is coronary flow reduced with increasing heart rate?
Diastole decreases.
101
What is anginal chest pain caused by? Why?
```
Potassium ions
Hydrogen ions
Adenosine
Bradikynin
Prostaglandins
All are released in ischaemia and can activate pain fibres.
```
102
How can artherosclerosis cause angina?
Narrows coronary arteries restricting blood flow.
103
Outline the 3 types of angina.
Stable - Pain on exercise. Fixed coronary narrowing
Unstable - Pain on increasingly less exercise. Formation of thrombus/clot. Rosk of MI
Variant - Spasm of coronary arteries.
104
What are anti-anginal drugs used for?
Symptomatic relief.
105
What surgical treatments are used for treating angina?
Angioplasty - Mechanical widening of coronary vessels.
| Bypass - Grafting an artery next to the existing and using that instead.
106
What are the types of anti-anginal drugs?
Beta blockers
Organic nitrates
Calcium channel blockers
Potassium channel openers
107
How do beta blockers treat angina?
Decrease the force of contraction and heart rate hence decrease cardiac workload/output.
This decreases oxygen demand of the heart and increases the heart's efficiency (work/O2 consumption)
108
How do organic nitrates treat angina?
Cause vasodilation of coronary artery to improve coronary blood flow. (Nitrovasodilator action)
Cause vasodilation of large veins to decrease veinous return and hence workload.
Dilate arteries to decrease blood pressure.
Improve collateral flow in coronary circulation.
109
Give 3 examples of organic nitrates used in treatment of angina.
Glyceryl nitrate (Nitroglycerine)
Isosorbide mononitrate
Isosorbide dinitrate
110
Using what mechanisms do organic nitrates treat angina?
Converted into (NO2)- as they enter the vascular smooth muscle cell.
(NO2)- converted into NO which binds to thiols.
Forms R-SNO molecules.
R-SNO and NO used by guanylyl cyclase to convert GTP into cGMP
cGMP activates PKG which causes relaxation of smooth muscle.
111
How do calcium channel blockers treat angina?
Block calcium VGCs preventing CICR.
Decrease force of contraction and oxygen consumption in cardiac muscle.
Decrease force of contraction of vascular smooth muscle - vasodilation
112
Give 3 examples of calcium channel blockers and their site of action.
Verapamil - Mainly cardiac action
Diltiazem - Cardiac and smooth muscle
Dihydropyridines - Smooth muscle
113
What can calcium blockers be used for other than treating angina?
Treatment of arrhythmia.
| Treatment of hypertension.
114
How do potassium openers treat angina?
Open ATP-activated potassium channels.
Causes hyperpolarisation of the coronary arterial smooth muscle.
Hyperpolarisation causes closure of calcium channels.
Causes reduction of calcium entry hence vasodilation.
115
Give an example of a potassium channel opener.
Nicorandil.
116
What causes myocardial infarction?
Artherosclerosis in coronary arteries.
117
How is myocardial infarction induced?
Artherosclerosal plaques rupture.
Platelets adhere to exposed glycoproteins, activating themselves.
Platelets form a thrombus/clot which is reinforced by fibrin.
Blockage of coronary artery causes MI.
118
What inhibits thrombus formation?
Aspirin.
119
Which drugs may be used to prevent MI?
```
Anti-anginals (Nitrovasodilators)
Aspirin.
Statins.
Fibrinolytic agents.
Beta blockers
```
120
What are the aims of MI treatments?
Reduction of ischaemia
Decrease of coronary workload
Avoidance of arrhythmias.
121
What are the stages of acute MI?
Ventricular fibrillation.
| Cardiac arrest.
122
How is acute MI treated?
Defibrillation
| Adrenaline
123
How do nitrovasodilators treat MI? Give an example.
Dilate collateral vessels improving blood supply and reducing pain.
Dilate large vessels to reduce the load on heart.
IV glyceryl trinitrate (nitroglycerine)
124
How do fibrinolytic agents treat MI? Give an example.
Dissolve clot.
| Streptokinase (not an enzyme) complexes with plasminogen.
125
How do beta blockers treat MI?
Reduce sympathetic drive on beta-adrenoceptors.
Decrease cardiac work/atp usage
Decrease calcium entry
Decrease likelihood of arrhythmias by decreasing automaticity of quiescent tissue.
