CVS Flashcards
(310 cards)
1
Q
Describe the 3 factors that affect diffusion rate
A
Area: determined by capillary density
Diffusion Resistance: determined by the nature of the barrier & molecules diffusing, distance required to travel
Concentration Gradient: determined by flow of blood through the capillary.
2
Q
What’s the average range of blood flow through the entire system?
A
5.0 l/min (rest) to 25.0 l/min (strenuous exercise)
3
Q
What’s the level of blood flow that must be maintained to the brain at all times?
A
0.75 l/min
4
Q
Where does the blood lie in our body?
A
65% veins
20% heart and lungs
10% peripheral arteries
5% capillaries
5
Q
What’s the difference between arterioles and metarterioles?
A
In metarterioles the smooth muscle layer is not continuous, only present at sphincters
6
Q
Name the 3 major types of artery
A
Elastic conducting (widest) Muscular distributing (intermediate diameter) Arterioles (narrowest, diameter
7
Q
Name the 3 layers of the walls of arteries and veins
A
Tunica intima (next to lumen) Tunica media (intermediate) Tunica adventitia (outermost)
8
Q
Is vasoconstriction of muscular arteries controlled by sympathetic or parasympathetic nerve fibres?
A
Synpathetic
9
Q
What is an end artery?
A
A terminal artery supplying all or most of the blood to a body part without significant collateral circulation. If occluded there is insufficient blood supply to the dependent tissue
10
Q
Describe the 3 types of capillaries
A
Continuous - (most common) cells joined by tight or occluding junctions
Fenestrated - little interruptions exist across thin parts of the endothelium (in parts of gut, endocrine glands)
Sinusoidal (discontinuous) - larger diameter, slower blood flow. Gaps exist in the walls allowing whole cells to move between blood and tissue (in liver, spleen and bone marrow)
11
Q
What do pericytes do?
A
Form a branching network on the outer surface of the endothelium. Capable of dividing into muscle cells, fibroblasts, during angiogenesis, tumour growth or wound healing
12
Q
What are 3 possible routes of transport across the endothelial wall of a fenestrated capillary?
A
- Direct diffusion
- Diffusion through intercellular cleft
- Diffusion through fenestration
13
Q
Where is the preferred emigration site of leukocytes from the blood?
A
Postcapillary venules
14
Q
What are venae comitantes?
A
Deep paired veins that accompany one of the smaller arteries. The pulsing of the artery promotes venous return within the adjacent, parallel, paired veins. The 3 vessels are wrapped together in one sheath. E.g. brachial, ulnar, tibial comitantes
15
Q
Why do we need a cardiovascular system?
A
Most cells far away from source of O2 and nutrients, a system is required to carry such to cells and carry waste products away.
16
Q
Define systole
A
Contraction and ejection of blood from the ventricles
17
Q
Define diastole
A
Relaxation and filling of the ventricles
18
Q
For how long does a cardiac action potential last?
A
~280ms
Lasts the duration of a single contraction of the heart
19
Q
Where is the tricuspid valve located?
A
Between the right atrium and the right ventricle
20
Q
Where is the mitral valve located?
A
Between the left atrium and the left ventricle
21
Q
Where is the pulmonary valve located?
A
Between the right ventricle and the pulmonary artery
22
Q
Where is the aortic valve located?
A
Between the left ventricle and the aorta
23
Q
What are the cusps of the mitral and tricuspid valves attached to?
A
Attached from the valves to papillary muscles via chordae tendineae (prevents inversion of valves on systole)
24
Q
Name the 7 phases of the cardiac cycle
A
- Atrial contraction
- Isovolumetric contraction
- Rapid ejection
- Reduced ejection
- Isovolumetric relaxation
- Rapid filling
- Reduced filling
25
Why does atrial pressure initially decrease during rapid ejection?
Atrial base is pulled downwards as ventricle contracts
26
Give 3 things which may lead to congenital heart defects
1. Genetics (Marian's, downs, turners syndromes)
2. Environmental (teratogenicity from drugs, alcohol ect.)
3. Maternal infections (rubella, toxoplasmosis, diabetes)
27
How are congenital heart defects classified?
Acyanotic (left to right shunts)
Cyan optic (right to left shunts, complex)
28
What is the approximate resting membrane potential for a cardiac monocyte
-90mV
| Ek =-95mV
29
What's the major difference between cardiac action potentials and skeletal muscle action potentials?
Cardiac action potentials are much longer in duration (100ms compared to 0.5ms in skeletal)
30
What causes the 'plateau' in a cardiac action potential?
Opening of voltage gated Ca2+ channels
31
What causes the upstroke of a cardiac action potential?
Opening of voltage-gated Na+ channels
32
What is If?
Funny current!
33
What is repolarisation due to in the cardiac action potential?
Efflux of K+ through voltage-gated K+ channels
34
What causes the gradual increase in membrane potential of the funny current?
Influx of Na+ via HCN (Hyperpolarisation-activated Cyclic Nucleotide-gated channels). The more negative, the more it activates (activated at potentials
35
What causes the upstroke in the SA node action potential?
Opening of voltage gated Ca2+ channels
36
What causes the downstroke of the SA node action potential?
Opening of voltage-gated K+ channels
37
Give 3 features of cardiac muscle
```
Striated
Central nuclei
Intercolated discs connecting cells
Gap junctions (permit movement of ions and electrically couple cells)
Desmosomes rivet cells together
```
38
Where does Ca2+ come from when it is used to stimulate contraction of muscle?
25% enters across sarcolemma
| 75% released from SR (intracellular stores)
39
What type of receptor causes initial influx of Ca2+ in muscle upon depolorisation?
L-type Ca2+ channels
40
What occurs after localised Ca2+ entry has occurred upon depolorisation of a muscle cell?
Opening of CICR (Calcium-Induced Calcium Release) channels in the SR
There is a close link between L-type channels and Ca2+ release channels
41
What happens on relaxation of cardiac myocytes?
Ca2+ levels are returned to resting levels, mostly by pumping Ca2+ back into SR (via SERCA), some exits across cell membrane
42
How is contraction of vascular smooth muscle regulated?
Ca2+ binds to calmodulin - this activates MLCK (myosin light chain kinase). MLCK then phosphorylates the myosin light chain to permit interaction with actin.
43
How is relaxation of vascular smooth muscle achieved?
Myosin light chain phosphatase dephosphorylates the myosin light chain (constituently active)
44
What are the respective lengths of the pre and post ganglionic neurones in the parasympathetic (cranio-sacral outflow) system?
Pre-ganglionic: long
| Post-ganglionic: short
45
What are the respective lengths of the pre and post ganglionic neurones in the sympathetic (thoraco-lumbar outflow) system?
Pre-ganglionic: short
| Post-ganglionic: long
46
What neurotransmitter do preganglionic neurones release?
Acetylcholine ACh
Acts on nicotinic ACh receptors on the postganglionic neurone (receptors contain integral ion channel permeable to Na+ and K+)
47
What neurotransmitter do postganglionic sympathetic neurones usually release?
Noradrenaline (so are noradrenergic)
48
What neurotransmitter do postganglionic parasympathetic neurones usually release?
Acetylcholine (so are cholinergic)
49
Name an exception to the neurotransmitter released by postganglionic sympathetic neurones?
Innervation of sweat glands by postganglionic release of ACh which acts on muscadine can ACh receptors)
50
What do chromaffin cells of the adrenal medulla release?
Adrenal chromaffin cells release adrenaline into the blood stream.
51
What are the benefits of having different subtypes of receptors/in different tissues?
Allows for diversity of action
| Enables selectivity of drug action
52
Name 2 co-transmitters which may be released with noradrenaline or adrenaline at then postganglionic synapse with effector cells
```
Neuropeptide Y (NPY)
ATP
```
53
What type of ACh receptors are on effector cells?
Muscarinic
54
What type of ACh receptors are on postganglionic neurones (proximal/receiving end)?
Nicotinic
55
What does the ANS control in the cardiovascular system?
Heart rate (but does not initiate electrical activity)
Force of contraction of the heart
Peripheral resistance of blood vessels
56
What effect does sympathetic input to the heart have?
Positive chronotropic effect (increases heart rate)
Positive inotropic effect (increases force of contraction)
Acts mainly on beta1 adrenoreceptors, release noradrenaline
57
What happens to the If (funny current) if the heart rate speeds up?
Slope steepens
58
Which receptors of the heart mediate the sympathetic effect?
Beta1
| G protein coupled receptors, increase cAMP, speeds up pacemaker potential
59
Which receptors of the heart mediate the parasympathetic effect?
M2 receptors
| G protein coupled receptors, increase K+ conductance and decrease cAMP
60
What type of adrenoreceptors do most arteries and veins have?
Alpha1 (sympathetic)
| Coronary and skeletal muscle vasculature also have beta2 receptors
61
Has circulating adrenaline got higher affinity for beta 2 or alpha 1 receptors?
Beta2, therefore will preferentially bind to such.
62
What do activated beta2 adrenoreceptors cause?
Vasodilation
| Increases cAMP, produces PKA, opens K+ channels, inhibits MLCK, relaxation of smooth muscle
63
What do activated alpha1 adrenoreceptors cause?
Vasoconstriction
Stimulates IP3 production
Increase in [Ca2+]in from stores and via influx of Ca2+, contraction of smooth muscle
64
What are the name of the receptors for high pressure side of the system?
Baroreceptors
65
What are the name of the receptors for low pressure side of the system?
Atrial receptors
66
Define flow
The volume of fluid passing a given point over a unit time
67
Define velocity
The rate of movement of particles along the tube
68
Where does blood flow fastest?
Where the total cross sectional area is least
69
Describe laminar flow
Gradient of velocity from middle to edge of vessel (velocity is highest in the middle, fluid is stationary at the edge)
70
Describe turbulent flow
As mean velocity increases, flow eventually becomes turbulent. Velocity gradient breaks down, fluid tumbles over itself. Flow resistance greatly increased.
71
What does mean velocity depend on?
Viscosity of the fluid
| Radius of the tube
72
Define velocity
The extent to which fluid layers resist sliding over one another. The higher the viscosity, the slower the central layers will flow, and the lower the average velocity.
73
Give 2 potential causes of hyperviscosity syndrome
1. Abnormally high plasma protein levels (treatment: plasmapheresis)
2. Abnormally high RBC or WBC count (treatment: phlebotomy)
Note: underlying condition must be treated or HVS recurs.
74
How do you work out total resistance for resistances aligned in series?
Total resistance equals the sum of the individual resistances
75
How do you work out the total resistance for resistances aligned in parallel?
The reciprocal of the total resistance equals the sum of the reciprocal a of the individual resistance
76
Which vessels have the highest resistance?
Arterioles
77
When does blood flow become turbulent?
Flow velocity is high
Viscosity is low
Lumen of blood vessel is irregular (e.g. Athlerosclerosis)
78
What is a bruit?
Noise heard upon ausculation of turbulent bloodflow.
79
What happens to resistance in distensile vessels as blood pressure rises?
The vessel stretches, so resistance falls. The higher the pressure, the easier it is for blood to flow through.
80
Which vessels are the most distensible?
Veins
81
What is compliance?
The ability to distend and increase volume due to pressure increase
82
What is capacitance?
Measure of relative volume increase per unit increase in pressure C=V/P
Effectively the same as compliance
83
What is pressure?
Measure of mechanical energy gradient in blood that drives its flow round different parts of the system
84
What is total peripheral resistance (TPR)?
The sum of all arteriolar resistance
85
What is cardiac output?
Cardiac Output = Stroke Volume x Heart Rate
86
What is the 'Windkessel' effect?
Aortic compliance dampens pulsatile nature of systolic pressure wave. 'Smooths out' blood flow
87
What is the maximum arterial pressure called?
Systolic pressure (~120mmHg)
88
What is the minimum arterial pressure called?
Diastolic pressure (~80mmHg)
89
List 3 factors effecting systolic and diastolic pressure
1. Cardiac output SVxHR (how hard heart is pumping)
2. Arterial compliance ('stretchiness' of elastic arteries ~1.5-2%/mmHg)
3. Total Peripheral Resistance
90
What is pulse pressure?
The difference between systolic and diastolic pressure ~40mmHg
91
What is the average pressure?
Diastolic pressure + 1/3 pulse pressure
92
Does the cardiac system spend more time in systole of diastole?
Diastole (~0.55s)
| Compared to ~0.3s in systole
93
What controls the flow to capillary beds?
Arterioles and pre-capillary sphincters - 'resistance vessels'
94
What are the levels of vasomotor tone at rest?
High - tonic contraction of smooth muscle
95
How is contraction of vascular smooth muscle achieved?
Release of noradrenaline by sympathetic nervous system, acts on alpha-1 GPCRs causing Ca2+ influx, therefore contraction
96
How is vascular vasodilatation achieved?
Achieved by local vasodilator factors produced by metabolically active tissues e.g. H+, CO2, K+, lactate
These act to relax vascular smooth muscle
97
What is the difference between vasodilation and vasodilatation?
Vasodilation - vasodilation in absence of vasoconstrictive signal.
Vasodilatation - reduction/offset of active vasoconstriction in presence of ongoing vasoconstrictive signal.
98
What regulates right atrium filling, and therefore stroke volume?
Veins/great veins
99
What controls total peripheral resistance?
Arterioles
100
At rest, what is the approximate mean arterial blood pressure?
~95mmHg
101
Why is the mean arterial blood pressure ~95mmHg?
This value is 'engineered to humans' - provides adequate pressure to perfume and drive blood through whole vasculature, ensuring positive central venous pressure
Significant functional reserve still available - many capillary beds not perfused
102
If hypotensive, at what value would mean arterial blood pressure falling below would tissue perfusion become inadequate?
60mmHg
103
What is the acute effect on the whole CVS of standing up?
CVP falls directly -RA filling decreases
Stroke volume decreases (by starlings law)
Mean arterial pressure falls (by ~20-25mmHg)
Both arterial and venous pressure falling acutely
This is signalled via baroreceptors
HR then increased (by ~10-25bpm) in response
104
What is the effect on the CVS of massive haemorrhage?
Hypovolemic shock if residual blood volume
105
How does exercise aid circulation?
Contractile activity of skeletal muscle in exercise actively aids whole circulation of blood (up to 50% of energy required to drive blood in circulation can come from muscle activity in exercise)
106
What is the response of the CVS to eating a large meal?
Local GI vasodilation leads to decrease in TPR. Initial decrease in arterial pressure. Flow out liver increases, leading to rise in CVP - rise in RA filling, so cardiac output increases
Parasympathetic activity increases
Greater flow to GI
107
What determines arterial pressure?
Cardiac output
| Total peripheral resistance
108
What determines venous pressure?
Rate blood enters veins
| Rate heart pumps
109
What is stroke volume?
End Diastolic Volume - End Systolic Volume
110
What is the relationship between venous pressure and ventricular volume know as?
The ventricular compliance curve
111
What is starlings law of the heart?
The more the heart fills, the harder it contracts (up to a limit). The harder it contracts, the bigger the stroke volume.
Rises in venous pressure automatically lead to rises in stroke volume.
112
What is contractility?
The EFFICIENCY of contraction (not the force!)
113
What does how much the ventricle contracts depend upon?
How hard it contracts
| How hard it is to eject blood
114
What is the force of contraction dependent upon?
End diastolic volume (starlings law)
| Contractility
115
Why, in starlings law of the heart, does the stretch of ventricular muscle only increase force of contraction up to a limit?
Beyond said limit tissue is damaged
116
What determines the difficulty of ejecting blood?
Total peripheral resistance
| The harder it is to eject blood, the higher pressure rises in the arteries
117
What determines the end systolic volume?
The easier it is to eject blood, the more comes out in systole. So if arterial pressure falls, end systolic volume will fall, stroke volume will rise.
118
What will happen to stroke volume if venous pressure rises?
Stroke volume will rise
119
What will happen to stroke volume if arterial pressure rises?
Stroke volume will fall
120
How is autonomic outflow of the heart controlled?
Signals from baroreceptors
| Carotid sinus senses arterial pressure, sends signals to medulla which then controls the heart
121
How is heart rate increased?
Increased sympathetic activity
| Decreased parasympathetic activity
122
How is contractility increased?
Increased sympathetic activity
123
Where are rises in venous pressure detected?
Right atrium
Leads to reduced parasympathetic activity (therefore rise in HR)
'Bainbridge reflex'
124
What do rises in venous pressure cause?
Increased stroke volume (starlings law)
| Increased heart rate
125
What do falls in arterial pressure cause?
Increased stroke volume (sympathetic activity as well as direct effect)
Increased heart rate
126
What is the typical cardiac output range?
5-15 l/min
127
What's the typical heart rate range?
60-180 bpm
128
What's the typical stroke volume range?
60-150 ml
129
What is hyperemia?
The increase of blood flow to different tissues of the body
130
Describe the response of the CVS to eating a large meal
Increased activity of the gut leads to release of metabolites and local vasodilation.
TPR falls, so arterial pressure falls, venous pressure rises
Cardiac output rises (increased HR and CO)
Extra pumping of the heart reduces venous pressure and raises arterial pressure
Demand met, system stable
131
Describe the response of the CVS to standing up
On standing, blood pools in superficial veins of the legs due to gravity
Central venous pressure falls, therefore cardiac output falls also (due to starlings law)
Arterial pressure falls, baroreceptors detect fall in arterial pressure
HR raised, TPR increased
132
What is postural hypotension?
Failure of the CVS to cope with changes in bloodflow upon standing up
133
Describe the response of the CVS to haemorrhage
Reduced blood volume lowers venous pressure
Cardiac output falls due to starlings law
Arterial pressure falls
Baroreceptors detect fall in arterial pressure, increase HR, increase TPR
Rise in HR lowers venous pressure further (MAKING PROBLEM WORSE)
Venous pressure needs to be increased to fix problem, but HR can become very high
Veno-constriction occurs
Treatment is blood transfusion to replace lost volume
134
Describe the response of the CVS to exercise
Enormous increase in demand
'Muscle pumping' forces extra blood back to the heart
Increased venous pressure, decreased arterial pressure. If heart cannot cope risk of pulmonary oedema
Overfilling of ventricles prevented by a rise in heart rate - when venous pressure starts to rise HR is already high
Stroke volume kept down, but CO increased
Demand met - system stable
135
What deflection will depolorisation moving towards an electrode show?
Positive deflection from baseline
136
What deflection will depolarisation moving away from an electrode show?
Negative defection from baseline
137
After how long will cardiac cells start to repolorise?
~280ms
138
Which surface of the heart repolarises first?
```
Epicardial surface
(Endocardial surface repolarises last)
```
139
What deflection will repolorisation moving towards an electrode show?
Negative deflection from the baseline
140
What deflection will repolorisation moving away from an electrode show?
Positive deflection from the baseline
141
What does the amplitude of an ECG signal depend upon?
How much muscle is depolarising
| How directly towards the electrode the excitation is moving
142
What does the P wave show?
Atrial depolarisation
143
What does the Q wave show?
Septal depolarisation spreading to ventricle
144
What does the R wave show?
Main ventricular depolarisation
145
What does the S wave show?
End ventricular depolarisation
146
What does the T wave show?
Ventricular repolarisation
147
List possible confounders for ECG readings
Lead misplacement
Muscle contractions (e.g. Movement, shivering, talking, coughing)
Interference (e.g. Alternating current)
Poor electrical contact (e.g. sweat, cable pull, hair)
148
How many squares is one second on an ECG?
5 large
149
How do you calculate the rate of a regular rhythm from an ECG?
Divide 300 by no. of large squares of R-R interval
150
How do you calculate the rate of an irregular rhythm from an ECG?
Count the no. of QRS complexes in 6s, then multiply by 10
151
Approximately how long should the PR interval be?
0.12-0.20s
| 3-5 small boxes
152
Approximately how long should the QT interval be?
Male: less than 0.45
| Female : less than 0.47
153
What do you look at to assess the rhythm of an ECG?
The rhythm strip
154
What is the average no. bpm for normal sinus rhythm?
60-100 bpm
155
On an ECG, how much time is represented by 1 large square (5mm)?
0.2s
156
On an ECG, how much time is represented by 1 small square (1mm)?
0.04s
157
List some points to assess when interpreting the rhythm of an ECG
Assess P waves (indicates atrial depolarisation)
Calculate PR interval (estimates conduction in AV node & bundle of his)
Assess the relationship between P waves and QRS complex (is every P wave followed by QRS/vice versa?)
Assess QRS complex (narrow? - rhythm originating in atria/AVN. Broad? - rhythm originating in ventricles)
158
What is a normal QRS complex width?
Less than or equal to 3 small boxes (0.12s)
159
What is the normal PR interval?
3-5 small boxes
| 0.12-0.20s
160
Describe atrial fibrillation
Atrial depolarisation chaotic - leads to loss of normal atrial contraction (atria quivering not contracting)
Impulses conducted irregularly to ventricles
Due to multiple abnormal atrial pacemakers discharging randomly
Ventricular depolarisation normal via his-purkinje system, hence narrow QRS complexes
Pulse and heart rate irregularly irregular
161
Are P waves present in atrial fibrillation?
No, as no atrial depolarisation occurs
162
What does the P-R interval show?
The time taken for conduction of impulse to ventricles
| Should be 3-5 small squares (0.12-0.2s)
163
Where do you measure a P-R interval from?
The start of the P wave to the start of the QRS complex
164
Describe a 1st degree heart block
Slow conduction in AV node and His bundle due to ischaemia or degenerative change
PR interval prolonged (>5 small squares/0.2s)
QRS/P wave both normal
165
Describe a type 1 second degree heart block (AKA Mobitz type 1 HB / Wenkebach phenomenon)
Progressive lengthening of PR interval till one P is not conducted (enabling AVN to recover). Cycle then repeats
166
Describe type 2 second degree heart block
Sudden lack of conduction of a beat (dropped QRS)
High risk of progression to complete heart block, requires insertion of a pacemaker
PR interval normal
167
Describe a third degree heart block
P waves normal, but not conducted to ventricle. Ventricular pacemaker takes over 'ventricular escape rhythm', rate is very slow (~30-40bpm). Usually wide QRS complexes.
Heart rate is too slow to maintain blood pressure and perfusion - urgent pacemaker insertion required
168
What are ectopic foci?
Abnormal pacemaker sites within the heart muscle that display automaticity. They are normally suppressed by the higher rate of the SA node (overdrive suppression). Can occur within the atria (atrial ectopics) or ventricles (ventricular ectopics)
169
Describe the characteristics of ventricular ectopic beats
Ectopic focus is in ventricle; depolarisation spreads through muscle, not via the Purkinje system. Therefore much slower depolarisation of ventricle. Wide QRS complex, different in shape to usual QRS.
170
A run of 3 or more consecutive ventricular ectopics is defined as....
Ventricular Tachycardia (VT)
171
Describe ventricular fibrillation
Abnormal, chaotic, fast, ventricular depolarisation from impulses arising in numerous ectopic sites in ventricular muscle. No co-ordinated contraction. No cardiac output, no pulse or heart beat. Cardiac arrest.
172
What do you look at on an ECG to assess 'structural' abnormalities
P-QRST in all 12 leads to identify problem/affected part of the heart.
173
What is a 'lead' in an ECG?
An electrical view of the heart
174
In what plane do the limb leads view the heart?
Vertical plane
175
In what plane do the chest leads view the heart?
Horizontal plane
176
Describe how partial occlusion of coronary arteries may present
Poor myocardial perfusion particularly on exercise - pain on exercise (angina)
ECG often normal at rest, but changes seen on exercise
177
Name 3 ECG features of a fully evolved myocardial infarction, in ECG leads facing the infarct end area.
1. Q waves, due to myocardial necrosis
2. ST segment elevation, due to subepicardial injury
3. T wave inversion
178
Describe the exercise ECG of a patient with angina
Sub-endocardial ischaemia causing ST depression in ECG leads facing the affected area/s
179
What are pathological Q waves?
Q waves of more than 0.04s (1small square) / >2mm deep. Present in full thickness myocardial infarction. Remain after other changes have been resolved.
180
What is the cardiac axis?
The average (overall) direction of spread of the ventricular depolarisation
181
In which direction is the cardiac axis usually?
Downward and to the left, between -30 and +90 degrees
182
What is left axis deviation associated with?
Left ventricular hypertrophy (LVH)
| Conduction blocks in anterior part of the left bundle branch
183
What is right axis deviation associated with?
Right ventricle hypertrophy
184
What would axis deviation of >+90 degrees be?
To the right
| 'Reaching'
185
Give the 8 points to give when reporting an ECG
```
Rate
Rhythm
Conduction intervals (PR, QRS, QT)
Axis (several methods of calculating this)
P wave (LA or RA enlargement)
Description of QRS complex
ST segment
T wave
```
186
In which direction is the shunt in a cyanotic heart defect?
Right to left
| Generally complex issues!
187
In which direction is the shunt in an acyanotic heart defect?
Left to right
188
Give some examples of what drugs might be used to treat, with regards to cardiovascular diseases
```
Arrhythmias
Heart failure
Angina
Hypertension
Risk of thrombus formation
```
189
Give examples of what drugs can alter, with regards to the cardiovascular system
The rate a rhythm of the heart
Force of myocardial contraction
Peripheral resistance and blood flow
Blood volume (via kidneys)
190
Give 3 possible causes of arrhythmias
Ectopic pacemaker activity
Afterdepolarisations
Re-entry loop
191
What are the 4 basic classes of anti-arrhythmic drugs?
1. Drugs that block voltage-sensitive sodium channels
2. Antagonists of beta-adrenoreceptors
3. Drugs that block potassium channels
4. Drugs that block calcium channels
192
Give an example of a a drug with blocks voltage-gated Na+ channels (class 1)
Lidocaine
193
How does lidocaine work, and when would it be used?
Blocks open/inactive Na+ channels, dissociates rapidly in time for new AP. Prevents automatic firing of depolarised ventricular tissue, little effect on normal cardiac tissue. Used if patient shows signs of ventricular tachycardia, given intravenously.
194
Give example(s) of beta adrenoreceptor antagonist drugs (class 2)
Propranolol
| Atenolol (beta blockers)
195
How do beta adrenoreceptor antagonist drugs (class 2) work?
Block sympathetic action (noradrenaline binding to beta adrenoreceptors in the heart). Decrease slope of pacemaker potential in SA. Reduces O2 demand. Can prevent supraventricular tachycardias
196
How do drugs that block K+ channels work?
Prolongs the AP, lengthening ARP, preventing new AP occurring too soon
197
Why aren't drugs that block K+ channels used all that much?
Can be pro-arrhythmic
198
What is the exception for drugs that block K+ channels, and what is it used for?
Amiodarone
Has other actions in addition to blocking K+ channels
Used to treat tachycardia associated with Wolff-Parkinson-White syndrome
199
Give an example of a drug which blocks Ca2+ channels
Verapamil
200
How do drugs which blocks Ca2+ channels work?
Decrease slope of AP at SA node, decreases AV nodal conduction, decrease force of contraction
Also some coronary and peripheral vasodilation
201
What effect do dihydropyridine Ca2+ channel blockers have on the CVS?
They are not effective in preventing arrhythmias, however do act on vascular smooth muscle (different types of L-type Ca2+ channels)
E.g. Amlopidine, felopidine, nicardipine
202
What does Adenosine act upon?
Produced endogenously but can also be administered intravenously. Acts on alpha 1 receptors at AV node
203
What is the effect of adenosine on the CVS?
Enhances K+ conductance (hyper polarises cells of conducting tissue)
Anti-arrhythmic drug, but doesn't fit into any of the 4 basic categories
204
Define heart failure
Chronic failure of the heart of provide sufficient output to meet the bodies requirements
205
What can drugs used to treat heart failure target?
Positive inotropic increase cardiac output (improves symptoms, but not long term outcome)
Drugs which reduce work load of the heart
206
Give two types of drug which are used in heart failure which have a positive inotropic effect so increase cardiac output
Cardiac glycosides
| Beta-adrenergic agonists
207
How do cardiac glycosides work?
Block Na+/K+ ATPase, resulting in a rise in intracellular Na+. Therefore less Ca2+ extrusion occurs via Na+/Ca2+ exchanger. Rise in intracellular Ca2+, so increased force of contraction.
Also cause increased vagal activity (slows AV conduction, slows heart rate).
208
What drugs increase myocardial contractility, and give an example
Beta-adrenoreceptor agonists
| E.g. Dobutamine (acts on beta 1 receptors)
209
What is dobutamine used for? What does it do?
Cardio genie shock
Acute but reversible heart failure, e.g. Following cardiac surgery
Increases myocardial contractility by acting as an agonist to beta 1 receptors
210
What do ACE inhibitors do? How?
Reduce the workload of the heart by inhibiting the action of angiotensin converting enzyme (thus preventing the conversion of angiotensin 1 to angiotensin 2, which increases Na+ and H2O retention by kidneys and is a vasoconstrictor)
Therefore decreases vasomotor tone, and blood volume, reducing after load and preload of heart,
211
What drugs reduce the workload of the heart?
```
ACE inhibitors
Beta adrenoreceptor antagonists (beta blockers)
Diuretics
Ca2+ channel antagonists
Organic nitrates
```
212
What two mechanisms are used for treating angina?
Reduce workload of the heart
| Improve the blood supply to the heart
213
What type of drugs are used to improve the blood supply to the heart?
Organic nitrates
| Ca2+ channel antagonists
214
How do organic nitrates work?
In the body, react with thiols (-SH group) in vascular smooth muscl, causing NO2- to be released. NO2- is reduced to NO (nitric oxide, powerful vasodilator)
215
How does NO (nitric oxide) cause vasodilation?
NO activates guanylate cyclase
Increases cGMP
Lowers intracellular Ca2+ conc.
Causes relaxation of vascular smooth muscle
216
How does vasodilation relieve symptoms of angina?
Primary action - venodilation lowers preload, reducing work load of heart, heart fills less therefore force of contraction reduced (starlings law), lowering O2 demand
Secondary action - action on coronary arteries improves O2 delivery to ischaemic myocardium (acts on collateral arteries rather than arterioles)
217
What parts of the vascular system does NO dilate?
Dilate collaterals
218
What heart conditions are at a particular risk of thrombus formation?
Atrial fibrillation
Acute MI
Mechanical prosthetic heart valves
219
Name some anticoagulant drugs
Heparin
Fractionated heparin
Warfarin
220
How does heparin work?
Given intravenously
Inhibits thrombin
Used acutely for short term action
(Fractionated heparin given subcutaneously)
221
How does warfarin work?
Agonises action of vitamin K, can be used long term
222
Name an antiplatelet drug, and suggest when it may be used
Aspirin
| Used following acute MI of high risk of MI
223
How may blood pressure be calculated?
Flow X resistance
| CO X TPR
224
What possible targets are there for treating high blood pressure
Lower blood volume (decreases CO via starlings law)
Lower cardiac output directly
Lower peripheral resistance
225
How long should the QRS interval be?
0.08 - 0.10 s
226
How is the progression of heart failure classified?
Class 1: No symptomatic limitation of physical activity
Class 2: Slight limitation of physical activity (ordinary physical activity results in symptoms). No symptoms on rest
Class 3: Marked limitation of physical activity (less than ordinary physical activity results in symptoms). No symptoms at rest
Class 4: inability to carry out any physical activity without symptoms. Discomfort increases with any degree of physical activity. May have symptoms at rest
227
What should cardiac output be?
~5 l/min
228
What should strove volume be?
~75 ml
229
What should left ventricle end systolic volume be?
~75 ml
230
What should left ventricle end diasystolic volume be?
~150 ml
231
What should the ejection fraction be?
50% +
| Less than 40% = bad
232
What structural heart changes may occur in heart failure?
Loss of muscle
Uncoordinated or abnormal myocardial contraction (ECG changes)
Changes to the extracellular matrix (increase in collagen 5-->25%, slippage of myocardial fibre orientation)
Change of cellular structure and function (myocyte hypertrophy, Sarcoplasmic reticulum dysfunction, changes to Ca2+ availability, myocytolysis and vacuolation of cells)
233
What does elevated angiotensin 2 do?
Potent vasoconstrictor
Promotes LVH and myocyte dysfunction
Promotes Na+/H2O retention
Stimulates thirst by central action
234
What is RAAS?
Renin-Angiotensin-Aldosterone System
235
What are the long term effects of having the sympathetic nervous system compensate for poor CO?
Beta-adrenergic receptors are down-regulated/uncoupled
Noradrenaline induces cardiac hypertrophy/myocyte apoptosis via alpha receptors.
Induces up-regulation of RAAS
Reduction in heart rate variability
236
What are released upon atrial stretching?
Natriuretic hormones
237
What do Natriuretic hormones do?
Decrease Na+ reabsorption in the collecting duct
Inhibits secretion of renin and aldosterone
Systemic arterial and venous vasodilatation
Predominate renal action, constricts afferent and vasodilate a efferent arteries
238
Why is ADH increased in heart failure?
Increased H2O retention, tachycardia, reduced systemic resistance, resulting in increased CO
239
What secretes endothelin?
Vascular endothelial cells
240
What does endothelin do?
Potent systemic and renal vasoconstrictor acting via autocrine (local) activity, thus activating RAAS. Poor prognosis sign
241
What do prostaglandins E2 and I2 do?
Act as vasodilators on afferent renal arterioles to attenuate effects of NA/RAAS.
Stimulated by NA and RAAS
242
Why is endothelial cell production of NO reduced in HF?
NO synthase may be blunted. Resulting loss of vasodilatation balance
243
What does bradykinin do?
Promotes natriuresis and vasodilatation. Stimulates production of prostaglandins.
Gets broken down in the body, this is prevented by ACE inhibitors.
244
What is tumour necrosis factor (alpha-TNF)?
Increased levels in HF. Depresses myocardial function. Stimulates NO synthase
245
Describe changes that may occur to skeletal muscle as a result of HF
Decrease in skeletal muscle blood flow results in decreased skeletal muscle mass (cachexia), affecting all muscles including limbs and respiratory.
Abnormalities of structure and function
Contributes to fatigue and exercise intolerance
246
Describe the renal effects that may occur in HF
Initially GFR is maintained by haemodynamic changes at the glomerulus
Increased Na+/H2O retention due to neuro-hormonal activation
In severe HF, renal blood flow falls, leading to reduced GFR and a subsequent rise in serum urea and creatinine
This can be exacerberated by treatment inhibiting the actions of angiotensin 2.
247
How may chronic HF cause anaemia?
In unhealthy kidneys - produce less erythropoietin
248
Describe the signs and symptoms of left heart failure
- Fatigue, exertional dyspnoear (breathlessness)
- Tachycardia
- Cardiomegaly (displaced apex beat, may be sustained)
- 3rd or 4th heart sound ('gallop rhythm')
- Functional murmur of mitral regurgitation
- Basal pulmonary crackles
- Peripheral oedema
249
What is the most common cause of right heart failure?
Secondary to left heart failure
250
What are some possible causes of right heart failure?
Chronic lung disease
Pulmonary embolism/pulmonary hypertension
Pulmonary/tricuspid valvular disease
Left-right shunts (ASD/VSD)
Isolated right ventricular cardiomyopathy (disease of the heart)
251
What are the signs and symptoms of right heart failure?
- Relate to distension and fluid accumulation in areas drained by systemic veins
- fatigue, dyspnoear, anorexia, nausea
- increased jugular venous pressure
- tender, smooth hepatic enlargement
- dependent pitting oedema
- ascites
- pleural effusion
252
What are the principles of managing heart failure?
Correct the underlying cause
Use non-pharmacological measures (reduce salt, alcohol, BP, increase aerobic exercise)
Pharmacological measures (symptomatic improvement, delay progression of HF, reduce mortality)
Treat complications/associated conditions/cardiovascular risk,me.g. Arrhythmias
253
How do you calculate mean arterial blood pressure?
maBP = HR X SV X TPR
254
50% reduction in diameter of a vessel resets in what fraction of the original flow?
1/16
255
What % occlusion of coronary artery flow is required to result in compromised blood flow only when O2 demand increases?
Over 70% occlusion
256
What % occlusion of coronary artery flow is required to result in ischaemia at rest?
90% occlusion
257
When HR increases, what shortens?
Diastole
258
What ECG change may be seen with ischaemic heart disease?
ST depression in effected leads of the heart
259
Describe stable angina
Brought on by exercise, relieved by rest
260
Describe unstable angina
Rapid onset of pain at rest
ST depression/T wave inversion
No detectable necrosis
261
What is a STEMI MI?
Necrosis of full thickness of myocardial wall
262
What ECG changes might be seen in a STEMI MI?
ST segment elevation, Q waves, T wave inversion
263
What ECG changes might be seen in an NSTEMI MI?
More limited damage to myocoardium
ST depression
Inverted T waves
264
What do you look for in the blood to confirm an MI?
Creatinine kinase
| Specific isoforms of troponin (I and T)
265
Define cardiac arrest
Unresponsiveness associated with a lack of pulse
266
What is cardiac arrest due to asystole?
Loss of electrical and mechanical activity
267
What is cardiac arrest due to (PEA)?
Pulseless Electrical Activity
268
What is cardiac arrest due to ventricular fibrillation?
Uncoordinated electrical activity
Most common form of cardiac arrest, often following MI, electrical imbalance or some arrhythmias (e.g. Long QT/Torsades de pointes)
269
What is the treatment for cardiac arrest?
Basic life support (chest compressions/external ventilation)
Advanced life support (defibrillation, depolarises cells putting the in refractory period, enabling coordinated electrical activity to restart)
Adrenaline (enhances myocardial function, increases peripheral resistance)
270
What is haemodynamic shock?
An acute condition of inadequate bloodflow throughout the body. Catastrophic fall in arterial blood pressure leads to circulatory shock
271
What things might haemodynamic shock result from?
Fall in CO (pump failure, mechanical - pump can't fill, or loss of blood volume), or fall in TPR (massive vasodilation)
272
What is cardiogenic shock?
Pump failure - ventricle cannot empty properly
273
What is mechanical shock?
Obstructive - ventricle cannot fill properly
274
What is hypovolaemic shock?
Reduced blood volume leads to poor venous return
275
What are some potential causes of cardiogenic shock?
Post MI
Due to serious arrhythmias
Acute worsening of heart failure
276
What are the characteristics of cardiogenic shock?
Dramatic drop in arterial BP
Central venous pressure may be normal or raised
Tissues poorly perfused (including coronary arteries, excuberating problem. Kidneys, resulting in oliguria)
277
What is mechanical shock, cardiac tamponade?
Fluid build up in pericardial space, restricts filling of the heart, limits end diastolic volume. Effects both left and right heart.
278
What are the characteristics of mechanical shock, cardiac tamponade?
High central venous pressure
Low arterial blood pressure
Continued electrical activity, heart attempts to beat
279
What is mechanical shock, pulmonary embolism?
Embolus occludes a large pulmonary artery
280
What are the characteristics of mechanical shock, pulmonary embolism?
```
Pulmonary artery pressure is high
Right ventricle cannot empty
Central venous pressure is high
Reduced return of blood to left heart
Limits filling of left heart
Left atrial pressure is low
Arterial blood pressure is low
Results in shock (also chest pain, dyspnoea)
```
281
What are possible causes of hypovolaemic shock?
Haemorrhage
Severe burns
Severe diarrhoea/vomiting
Loss of Na+
282
What are the stages of hypovolaemic shock?
Less than 20% blood - unlikely to cause shock
20-30% - some signs of shock response
30-40% - substantial decrease in mean arterial BP and serious shock response
283
What does the severity of hypovolaemic shock depend upon?
Volume of blood lost
| Speed of blood loss
284
Describe the sequence of events resulting in hypovolaemic shock?
```
Venous pressure falls
Cardiac output falls (starlings law)
Arterial pressure falls
Detected by baroreceptors - causing sympathetic stimulation and compensatory response
Tachycardia
Increased force of contraction
Peripheral vasoconstriction
Venoconstriction
```
285
What is internal transfusion? (In hypovolaemic shock)
Increased peripheral resistance reduces the capillary hydrostatic pressure, net movement of fluid into capillaries
286
What are the characteristics of hypovolaemic shock?
Tachycardia
Weak pulse
Pale skin
Cold, clammy extremities
287
What is the decompensation response in shock?
```
Tissue damage due to hypoxia
Release of chemical mediators (vasodilators)
TPR falls
Blood pressure falls dramatically
Vital organs can no longer be perfused
Multi organ failure
Death
```
288
What is distributive shock?
Low resistance shock (normovolaemic). Profound peripheral vasodilation decreases TPR. Blood volume is constant, but volume of circulation has increased.
289
Describe how toxic (septic) shock (septicaemia) occurs
Endotoxins released by circulating bacteria cause profound vasodilation - dramatic fall in TPR
Fall in arterial pressure
Impaired perfusion of vital organs
Also capillaries become leaky (reduction in blood volume)
Decreased arterial pressure is detected by baroreceptors, which increase sympathetic output, however vasoconstrictor effect is overridden by mediators of vasodilation (no vasoconstriction)
290
Describe the characteristics of toxic (septic) shock (septicaemia)
Tachycardia
| Warm, red extremities (although in the very later stages of toxic shock, vasoconstriction)
291
What causes anaphylactic shock?
Severe allergic reactions
292
Describe the process of anaphylactic shock
Release of histamine from mast calls (+ other mediators)
Powerful vasodilator effect (fall in TPR)
Dramatic drop in arterial pressure (increased sympathetic response. CO increased, but can't overcome vasodilation)
Impaired perfusion of vital organs
Mediators also cause bronchoconstriction and laryngeal oedema (causing difficulty breathing)
293
What are the characteristics of anaphylactic shock?
Difficulty breathing
Collapsed
Tachycardia
Red, warm extremities
294
What is the treatment of anaphylactic shock?
Adrenaline, in high enough dose to cause vasoconstriction via alpha1-adrenoceptors
295
What are the 3 places in the body which regulate BP?
Kidneys (regulation of blood volume, effects SV)
Heart (regulates CO via rate and force)
Vasculature (regulate TPR)
296
What are the names of the major coronary veins?
Great, middle, small. Drain into the coronary sinus
297
What is a hypoplastic left heart?
Congenital underdevelopment of the left heart. Ascending aorta is very small, right ventricle supports systemic circulation - obligatory right to left shunt.
298
When is If activated?
At membrane potentials less than -50mV (the more negative, the more activated)
299
What channels cause the If?
Hyperpolarisation-activated cyclic nucleotide-gated channels (HCN channels)
300
What do gap junctions permit?
The movement of ions and electrically couple cells
301
Parasympathetic nervous input to the heart is via which nerve?
The 10th cranial (vagus) nerve. Preganglionic fibres synapse with postganglionic fibres on epicardial surface/within walls of heart at the SA/AV nodes. Release ACh which acts upon M2 receptors
302
How is the sympathetic effect upon the heart carried out?
NA is released at beta1 adrenoreceptors. Increases CO via increasing cAMP, which activates PKA. Phosphorylation of Ca2+ channels, so increased Ca2+ entry during plateau of AP. Increased Ca2+ uptake in SR, increased sensitivity to Ca2+
303
What is the most important factor for ensuring adequate perfusion?
Local metabolites
304
How do beta2 receptors exert their effect upon vasculature?
Cause vasodilation by increasing cAMP, which activates PKA. This causes K+ channels to open, and MLCK inhibition
305
How do alpha1 receptors exert their effect upon vasculature?
Cause vasoconstriction. Increase IP3 production, so increases concentration of Ca2+ in cells, increasing the force of contraction
306
What is the normal range for the cardiac axis?
-30 to +90
307
What molecules can freely diffuse the blood brain barrier?
Lipid soluble molecules e.g. O2/CO2. Lipid insoluble molecules cannot
308
What forms the blood brain barrier?
Cerebral capillaries
309
What happens to the amount of ADH during heart failure
Increases (increased H2O retention, increasing CO)
310
What are the long term responses to restore blood volume?
RAAS/ADH
| 20% blood loss can be restored within 3 days with adequate salts and H2O
