CVS SEM 2 Flashcards
(653 cards)
1
Q
Above what distance would diffusion be too slow?
A
1mm
2
Q
How is O2 tranported through the body?
A
Convection
3
Q
Define convection
A
Mass movement of fluid caused by pressure difference
4
Q
Where is electrical activity generated in the heart?
A
The SA node
5
Q
What happens to electrical activity generated in the SAN?
A
Electrical activity spreads out into the atria, via the gap junction, and towards the AV node
6
Q
Why is conduction delayed at the AVN?
A
To allow for correct filling of the ventricles
7
Q
What’s the electrical activity conducted through after the AVN?
A
Conduction occurs rapidly through the bundle of His and simultaneously up through Purkinje fibres in the ventricle walls from the apex of the heart, causing ventricular contraction
8
Q
What does the P wave of an ECG signify?
A
Atrial depolarisation
9
Q
What does the PR segment of an ECG signify?
A
AV nodal delay
10
Q
What does the QRS complex of an ECG signify?
A
Ventricular depolarisation (and simultaneous atrial repolarisation)
11
Q
What does the ST segment of an ECG signify?
A
Time during which the ventricles are contracting and emptying
12
Q
What does the T wave of an ECG signify?
A
Ventricular repolarisation
13
Q
What does the TP interval of an ECG signify?
A
The time during which the ventricles are relaxing and filling
14
Q
What causes heart valves to open or close?
A
Changes in pressure in the chambers
15
Q
Describe ventricular filling
A
Blood moves from the atria into the ventricles due to greater pressure in the atria causing the tricuspid and mitral valves to open. Filling of the ventricles is aided by atrial systole
16
Q
Describe isovolumetric contraction
A
Pressure in the ventricles becomes greater than in the atria, causing the tricuspid and mitral valves to close. The ventricles contract and pressure greatly increases
17
Q
Describe ejection
A
Pressure in the ventricles becomes greater than that in the aorta and pulmonary trunk. The aortic and pulmonary valves open and blood is ejected into the aorta and pulmonary trunk. More blood arrives at the atria
18
Q
Describe isovolumetric relaxation
A
The pressure becomes greater in the aorta and pulmonary trunk than in the ventricles, so the aortic and pulmonary valves close and the ventricles relax to receive more blood
19
Q
What proportion of blood is forced out of the ventricles in a normal systole?
A
About 2/3
20
Q
What’s the end diastolic volume in a healthy person?
A
EDV is around 120ml
21
Q
What’s the end systolic volume in a healthy person?
A
ESV is around 40ml
22
Q
What is normal stroke volume in a healthy person?
A
80ml
23
Q
What’s the equation of stroke volume?
A
EDV- ESV
24
Q
What’s the ejection fraction?
A
SV/EDV
25
What is the equation for stroke work?
Change in ventricular pressure x change in volume
26
What part of a ventricular pressure-volume loop curve signifies stroke work?
The area under the curve
27
What causes heart sounds?
S1- The closure of the tricuspid and mitral valves at the beginning of ventricular systole
S2- Closure of the aortic and pulmonary valves at the beginning of ventricular diastole
28
What causes S3 heart sounds?
Turbulent blood flow into the ventricles, which is detected just after S2 and is called 'ventricular gallop'
29
What is S4?
A pathological heart sound caused by forceful atrial contraction against a stiff ventricle at the end of diastole
30
What is cardiac output?
The volume of blood ejection from the heart per minute.
31
What's the equation for blood flow?
CO= BP/TPR
32
What is preload of the heart?
Stretching of the heart during diastole due to filling pressure
33
What is contractility?
Strength of contraction at a given diastolic loading due to sympathetic nerves and circulating adrenaline increasing Ca2+ concentration
34
What is after load?
The pressure the heart must work against to eject blood in systole
35
What is systole?
The period of ventricular contraction that occurs between the first and second heart sounds, causing the ejection of blood into the aorta and pulmonary trunk
36
What is diastole?
The period of relaxation of heart muscle and simultaneous refilling of the atria
37
What is energy of contraction?
The amount of work required to generate stroke volume, which depends on Starling's law and contractility
38
What's energy of contraction of cardiac muscle proportional to?
Muscle fibre length at rest
39
What is Starling's law of the heart?
Energy of contraction is proportional to the muscle fibre length at rest. Greater stretch of the ventricle in diastole gives greater energy of contraction, so greater SV is achieved in systole
40
How does increase in EDV affect stroke volume?
Increase in EDV increases stroke volume, up to a point at which stroke volume plateaus, and after which SV decreases due to overstretching of the heart from excess filling
41
What's responsible for the fall in cardiac output following a drop in blood volume?
Preload
42
What leads to the fall in cardiac output during orthostasis, that causes postural hypertension?
Preload
43
What determines after load?
Wall stress- force through the heart wall
44
What does Laplace's law involve and what's the equation?
```
Laplace's law involved the parameters that determine after load
S= P x r/2w
S- wall stress
P- pressure
r-radius
w- wall thickness
```
45
How does increase in pressure affect wall stress?
Increase
46
How does increase in wall thickness affect wall stress?
Reduce
47
How does increase in radius affect wall stress?
Increase
48
Why does small ventricular radius decrease afterload?
Small ventricular radius means greater wall curvature, more wall stress directed towards the centre of the chamber and better ejection
49
How does Laplace's law oppose Starling's law at rest?
Increasing preload increases chamber radius. This increases after load, opposing ejection of blood from a full chamber.
50
What happens in a healthy heart regarding Starilng's law and Laplace's law?
Starling's law overcomes Laplace's law to maintain ejection
51
What is phase 0 of the cardiac cycle?
Rapid depolarisation
52
What is phase 1 of the cardiac cycle?
Early repolarisation
53
What is phase 2 of the cardiac cycle?
The plateau phase
54
What is phase 3 of the cardiac cycle?
Rapid repolarisation
55
What is phase 4 of the cardiac cycle?
Resting phase
56
How does Laplace's law facilitate ejection during contraction?
Ventricular contraction decreases chamber radius. Laplace's law says this will reduce after load in the emptying chamber. This aids ejection during reduced ventricular ejection in phase 4
57
How does Laplace's law contribute to a failing heart?
In a failing heart, chambers are often dilated, so radius is increased. Ejection is reduced as there's greater after load opposing rejection
58
What does Laplace's law state?
Increased arterial blood pressure leads to increased after load, reducing ejection.
59
What's a consequence of chronic high arterial blood pressure?
Blood flow to end organs is poor because SV and CO are decreased and after load is increased
60
Define contractility
The strength of contraction at a given resting loading, due to sympathetic nerves and circulating adrenaline increasing Ca2+ concentration
61
What's the force of contraction proportional to?
The concentration of Ca2+
62
What's diastolic Ca2+ concentration?
Around 100nM
63
What is normal systole Ca2+ concentration?
Around 1uM
64
What's maximum systole Ca2+ concentration?
Around 10uM
65
What causes local Ca2+ influx in myocytes?
An action potential upstroke via Na+ ions depolarises T-tubules, opening VGCCs to allow Ca2+ influx
66
What does Ca2+ bind to on the SR for CICR?
Ca2+ binds to ryanodine receptors on the SR to trigger release of stored Ca2+ form the sarcoplasmic reticulum
67
What does Ca2+ bind to to trigger muscle contraction?
Ca2+ binds to troponin C, displacing it from the troponin-tropomyosin complex from myosin binding sites on actin to expose the active sites
68
How does greater Ca2+ concentration affect contractility?
More Ca2+ means more myosin binding sites on actin are exposed, so more cross bridges can form and contractions are stronger.
69
What does TnT do?
TnT binds to tropomyosin
70
What does TnI do?
TnI binds to actin filaments to hold tropomyosin in place
71
What does TnC do?
TnC binds to Ca2+
72
How does Ca2+ decrease in muscle tissue at the sub cellular level? 5 ways
AP downstroke via K+ ions repolarises T-tubules, closing VGCCs and decreasing Ca2+ concentration
No Ca2+ influx means no CICR. Ca2+ is extruded from cells by Na+/Ca2+ exchanger. Ca2+ is uptaken into the SR via Ca2+ ATPase and uptaken in mitochondria
73
How does decrease in Ca2+ affect muscle contraction?
Reduction in Ca2+ concentration means myosin head ATPase activity releases energy. The contraction mechanism is prevented by troponin binding back to tropomyosin and blocking active sites, preventing cross bridge formation.
74
What is hyperkalaemia?
A condition in which external K+ concentration is high (normal concentration is 3.5-5mM)
75
At what K+ concentration does the heart stop beating and why?
7-8mM. The membrane potential depolarises, reducing onset time and inactivating Na+ channels, so aptitude decreases and action potentials are shortened
76
How does increased H+ concentration affect contraction?
H+ competes with Ca2+ for troponin C binding sites, impairing contraction
77
How does low O2 levels affect contraction?
Hypoxia leads to local acidosis, impairing contraction due to raised H+ levels. Hypoxia also affects ion channels, causing depolarised membrane potential and making action potentials smaller, so contraction becomes poor
78
What's the name of the effect where contractility increases?
Positive inotropic effect
79
What's the name of the effect where relaxation increases?
Positive iusotropic effect
80
What's the name of the effect where heart rate increases?
Positive chronotropic effect
81
What's the name of the effect where conduction increases?
Positive dromotropic effect
82
How can high resting heart rate cause greater risk of CVD?
Higher heart rate means increased myocardial O2 consumption, which reduces coronary circulation perfusion time, which only occurs during diastole. Risk of arrhythmia and coronary artery plaque disruption are increased
83
How can phase 0 of the cardiac cycle be reduced?
Inhibition of VGCCs slows down the upstroke
84
How can phase 4 be increased?
Inhibition of funny channels means Ca2+ channels are activated slower
85
What are CCBs?
Ca2+ channel blockers
86
How do CCBs work?
CCBs sit in the pore of Ca2+ channels and block Ca2+ entry into sino-atrial cells to reduce heart rate
87
What are the 3 subtypes of CCB?
Dihydropyridines (vascular selective)
Diphenylalkylamines (cardiac selective)
Benzothiazepines (vascular + cardiac)
88
Name a dihydropyridine
Amlopdipine
89
Name a diphenylalkylamine
Verapamil
90
Name a benzothiazepine
Diltiazem
91
What property allows CCBs to be selective to cardiac or vascular Ca2+ channels?
Cardiac and vascular Ca2+ channels have slightly different structures
92
Why can CCBs worsen heart failure and cause heart block?
The AV node is needed for atria-ventricle conduction and CCBs have non-selective blocking actions on Ca2+ channels in cardiac myocytes
93
Name a funny channel blocker
Ivabradine
94
How does ivabradine work to lower heart rate?
Ivabradine is a selective inhibitor of funny channels in the SAN. It decreases the If current, reducing pacemaker potential frequency and decreasing the heart rate to reduce myocardial O2 demand
95
Why are ß1-adrenoreceptor blockers central drugs in treatment of angina?
ß-blockers such as atenolol reduce the action of the sympathetic nervous system on the SAN, preventing heart rate from increasing too much
96
Why shouldn't ß1-adrenoreceptor blockers be used in combination with CCBs?
Together, they can reduce contractility too much and produce too much bradycardia, leading to fatigue
97
How do Muscarinic receptor blockers work to increase heart rate?
They reduce the action of the parasympathetic nervous system on the SAN
98
Name 3 conditions muscarinic receptor blockers may be used for
COPD, IBS and overactive bladder
99
What's the name of a drug that increases contractility?
An inotropic agent
100
How is sympathetic control of the SAN regulated to increase heart rate?
Noradrenaline acts at ß1-adrenoreceptors on the SAN, activating the Gas system to produce cAMP and increase If channel activity
101
How is parasympathetic control of the SAN regulated to decrease heart rate?
Ach binds to M2 receptors on the SAN, acting at Gai protein to inhibit adenylate cyclase, reduce cAMP production and decrease If channel activity
102
How do ß1-adrenoreceptor blockers such as atenolol prevent heart rate from increasing too much?
They reduce the action of the sympathetic nervous system on the SAN, so they're central drugs in angina treatment
103
Why shouldn't ß1-adrenoreceptor blockers be used in combination with Ca2+ channel blockers?
Together, these can reduce contractility too much and produce too much bradycardia, leading to fatigue
104
What's a possible side effect of muscarinic receptor blockers?
Tachycardia and therefore increased O2 demands on the heart
105
What is the result of improperly maintained cardiac output in heart failure?
End organs are poorly perfused
106
Name 2 Gs-coupled receptor agonists
ß1-adrenoreceptor agonists
| PDE inhibitors
107
What heart condition are ß1-adrenoreceptors used to treat?
Acute heart failure
108
When would glucagon be used instead of ß1-adrenoreceptor agonists?
When the person is taking beta blockers, so adrenaline, dobutamine and dopamine would not work
109
Why aren't Gs agonists used in chronic heart failure?
They'd increase heart rate, myocardial work and O2 demand
110
Name a PDE inhibitor
Amrinone
111
What does PDE inhibitor stand for?
Phosphodiesterase inhibitor
112
How do PDE inhibitors work?
They cause a build up of cAMP, activation of PKA and increase in Ca2+ influx via VGCCs
113
When are PDE inhibitors used?
In severe chronic cases such as when waiting for a heart transplant
114
How do cardiac glycosides work?
They increase contractility by reducing Ca2+ extrusion
115
How does digoxin, a cardiac glycoside, work to increase contractility?
Digoxin inhibits Na+/K+ ATPase, so Na+ concentration builds up. There's then less extrusion of Ca2+ by the Na+/Ca2+ exchanger (NCX). As a result, there's more Ca2+ uptake into stores and greater CICR, so greater contraction
116
What are the 2 problems with Gs-coupled agonist-induced rise in Ca2+?
There's increased need for Ca2+-ATPase to reuptake more Ca2+ into SR stores, so there's more O2 consumption, which stresses the heart.
Also, Gs pathways increase heart rate, so they're pro-arrhythmogenic
117
What is a potential solution to Ca2+ related problems with Gs-coupled agonists?
Ca2+ sensitisers
118
Name 2 Ca2+ sensitisers
Levosimedan and Omecamtiv
119
How does levosimedan work?
Levosimedan binds to troponin C to increase the binding of Ca2+ to troponin C
120
How does omecamtiv work?
Omecamtiv increases actin-myosin interactions in absence of rise of Ca2+
121
Do Ca2+ sensitisers affect Ca2+ levels?
No
122
When are Ca2+ sensitisers used?
In decompensated heart failure
123
Why use ß-blockers in chronic heart failure when you'd expect that we'd need to promote ß-adrenoreceptor activity to increase inotropic effect? (4 points)
ß-blockers prevent overworking of a failing heart by slowing heart rate and increasing diastolic time, which increases coronary perfusion.
They prevent overworking of a failing heart by reducing contractility to reduce O2 demand, making the failing heart work more efficiently.
They prevent down-regulation of ß-adrenoreceptors caused by excess compensatory sympathetic nerve activity in heart failure, so more ß-adrenoreceptors are available for contractility.
They also prevent ß-adrenoreceptor-associated arrhythmia.
124
How do loop diuretics, thiazide diuretics and K+ sparing diuretics work to reduce cardiac output and blood pressure?
They cause you the excrete more fluid, reducing blood volume and reducing central venous pressure and stroke volume via Starling's law
125
How do ACE inhibitors and ARBs such as ramipril and losartan reduce TPR?
They reduce Ang II-induced vasoconstriction
126
What happens when Ang II-induced aldosterone release is reduced?
Blood volume and CO are reduced
127
What causes cardiac pain in angina?
Poor blood flow to the heart, often due to occlusion of the coronary arteries
128
How can cardiac pain from angina be alleviated?
Dilation of the coronary arteries to increase blood flow
129
What drug is commonly used for angina and how's it administered?
GTN (glyceryl trinitrate) is often administered as a sublingual spray
130
What is the significance of the CVS being a closed system?
What happens in one part of the CVS has a major impact on the rest, so, for example, reducing blood flow to 1 area increases the blood pressure in other areas
131
What does Darcy's law involve?
The role of pressure energy in blood flow
132
What's the equation of Darcy's law?
```
Q = (P1-P2)÷R
Q= flow
P1-P2= pressure difference
R= resistance to flow
```
133
What does Bernoulli's law involve?
The role of pressure, kinetic and potential energies in blood flow
134
What's the equation of Bernoulli's law?
Flow = Pressure + kinetic + potential
135
What is perfusion and its units?
Blood flow per given mass of tissue (ml/min/g)
136
How is velocity of blood flow calculated?
Blood flow divided by the cross-sectional area through which the blood flows (cm/s)
137
What slows blood flow velocity in arteries?
The branching of arteries
138
Where is blood flow the slowest?
In the capillaries
139
What are the 3 patterns of blood flow?
Laminar blood flow- most arteries, arterioles, veins and venules
Turbulent blood flow- ventricles, the aorta and atherosclerotic vessels
Bolus flow in capillaries
140
What does Reynold's number describe?
What determines change from laminar to turbulent flow
141
What's the equation for Reynold's number?
```
Re= pVD ÷ u
P= density
V= velocity
D= diameter
u= viscosity
```
142
Above what value of Reynold's number does turbulent blood flow occur?
2000
143
What's the equation for blood flow?
Blood flow = arterial blood pressure ÷ total peripheral resistance
144
Where is blood pressure the highest?
In the aortic trunk
145
What's normal systolic and diastolic pressure in the aorta?
120mmHg and 80mmHg
146
Name 4 factors that affect arterial blood pressure
Cardiac output
Properties of arteries
Peripheral resistance
Blood viscosity
147
Where is energy stored during LV ejection?
In the stretched elastin in the aorta and arteries
148
What happens to the stored energy during LV diastole?
The energy is returned to the blood as the walls of the aorta and arteries contract, sustaining diastolic blood pressure and blood flow when the heart is relaxed
149
What is pulse pressure?
Systolic pressure - diastolic pressure
| Represents the force the heart generates each time it contracts
150
What's the equation for pulse pressure?
Pulse pressure = stroke volume ÷ compliance
151
What happens if arterial compliance is decreased?
Decreased compliance means stroke volume increases systolic and pulse pressure disproportionately
152
Why does arterial compliance decrease in old people?
Arteries become stiffer via arteriosclerosis
153
How does decreased arterial compliance affect after load?
Decreased arterial compliance increases afterload, so the heart has to work harder
154
How does pulse pressure change as blood moves away from the aorta?
Pulse pressure increases
155
What is aortic stenosis?
Narrowing of the aortic valve, which gives a slower upstroke and indicates poor ejection
156
What is aortic regurgitation?
A leaky aortic valve which gives fast upstroke and poor diastolic runoff, that indicates blood entering the aorta/ventricles during diastole
157
What's a normal PR interval?
0.12-0.20 seconds
158
What's a normal QRS duration?
0.6-1.2 seconds
159
What's a normal QT interval?
>440ms in men
| > 460ms in women
160
What are the 2 types of arrhythmia?
Conduction abnormality arrhythmias and abnormal impulse initiation arrhythmias.
161
What causes conduction abnormality arrhythmias?
Blockages
162
What causes abnormal impulse initiation arrhythmias?
VT or ectopia
163
What is the result on an ECG if the SAN fails to initiate an impulse?
There's no P wave or QRS complex
164
What are conduction abnormalities characterised by?
A delay or interruption in conduction, which can be due to ischaemic heart disease or valve fibrosis
165
What is VT?
Ventricular tachycardia- a broad complex tachycardia originating in the ventricles
166
What's the most common variety of VT?
Monomorphic VT
167
How may VT cause hypertension, collapse and acute heart failure?
Ventricular tachycardia may impair cardiac output
168
What are the 3 basic arrhythmogenic mechanisms responsible for initiating tacharrhythmia?
Altered automaticity
Triggered activity where normal action potential suddenly swings positive again, allowing another depolarisation to occur abnormally
Re-entry
169
What's characteristic of atrial fibrillation on an ECG?
No distinct P waves, and there can also be an atrial saw-tooth pattern
170
What is SVT?
Supraventricular tachycardia- an abnormally fast heart rhythm resulting from improper electrical activity in the upper part of the heart.
171
What are the 4 main types of SVT?
Atrial fibrillation, paroxysmal SVT, atrial flutter and Wolff-Parkinson-White syndrome
172
What causes the ST depression in ischaemia?
Ischaemic myocytes have reduce membrane potentials compared to healthy myocytes. The difference in potential between the ischaemic region and healthy region displaces the ST segment. This is called the 'injury current' effect
173
What does TPR control?
Blood flow and blood pressure
174
What 3 things control TPR?
Poiseuille's law, myogenic response and blood viscosity
175
What does Poiseuille's law describe?
The parameters that govern TPR
176
What 3 factors determine TPR?
TPR is determined by radius ^4, pressure difference across vessels and length
177
Do capillaries control TPR?
No
178
Why do arterioles control TPR and not capillaries? 3 reasons
Radius of capillaries cannot be altered
There's less pressure drop across capillaries than arterioles due to less resistance to blood flow
Individual capillaries are short compared to arterioles
179
What reduces viscosity in capillaries?
Bolus flow
180
What is bolus flow?
Where erythrocytes travel singly, separated by segments of plasma
181
What feature of capillary arrangement means they have a low total resistance?
They're arranged in parallel
182
How is local blood flow through individual organs/ tissues mainly controlled?
Via changes in radius of arterioles supplying the organ/tissue
183
What's the name for intrinsic control?
Bayliss myogenic effect
184
How does Bayliss myogenic effect work?
Dilation of the micro vessel leads to ion influx (Na+, Ca2+) through stretch-sensitive membrane ion channels and, therefore, to contraction of the vessel smooth muscle cells to decrease radius
185
What are the 3 factors contributing to blood viscosity?
Velocity of blood, vessel diameter and haematocrit level
186
Describe veins
Veins are thin-walled, collapsible, voluminous vessels which contain 2/3 of the body's blood. They contain smooth muscle innervated by sympathetic nerves, so their radius can be controlled by constriction and relaxation
187
What happens when smooth muscle in veins is contracted (venoconstriction)?
Blood is expelled into central veins. Venous return, CVP and end-diastolic volume are increased, so stroke volume is increased
188
What's a typical venous pressure range in the limb veins or the heart?
5-10mmHg
189
What's typical central venous pressure?
0-5mmHg
190
What's typical venous pressure in the feet while standing?
90mmHg
191
Via what 3 mechanisms is blood returned to the heart?
Pressure gradient
Thoracic pump
Skeletal muscle pump
192
Describe the pressure gradient for returning blood to the heart
Pressure in the veins/venules is 10-90mmHg. In the IVC, SVC and right atrium, pressure is <5mmHg. Venous return = venous pressure - pressure in the right atrium ÷ venous resistance
193
Describe the thoracic pump and its role in returning blood to the heart
Inhalation causes the thoracic cavity to expand, leading to increased abdominal pressure, forcing blood upwards towards the heart. This increases right ventricular stroke volume, so blood flows faster with inhalation
194
Describe the skeletal muscle pump and its role in returning blood to the heart
Contraction of leg muscles returns blood into the right atrium. Retrograde flow is prevented by venous valves. When in the upright position, high local venous pressures are reduced. This reduces swelling of the feet and ankles. CVP and SV are increased during exercise.
195
Due to what 3 factors can standing still for a long time lead to fainting?
Gravity, heat-induced vasodilation and lack of muscle use
196
What's Bernoulli's theory?
Mechanical energy of flow is determined by pressure, kinetic energy and potential energy
197
Name some symptoms of arrhythmias
Palpitations, dizziness, fainting, fatigue, loss of consciousness, cardiac arrest, blood coagulation, stroke or MI
198
What can cause arrhythmias?
Cardiac ischaemia, heart failure, hypertension, coronary vasospasm, heart block or excess sympathetic stimulation
199
Arrhythmia can be ventricular or supra ventricular. Where would supra ventricular arrhythmia stem from?
The SAN, the atria or the AVN
200
How do arrhythmias affect cardiac output?
They lead to incorrect filling and ejection
201
What are the 2 mechanisms of arrhythmogenesis?
Abnormal impulse generation due to automatic rhythms, which leads to increased SAN activity and ectopic activity, causing triggered rhythms called early-after depolarisations (EADs) and delayed-after depolarisations (DADs)
Abnormal conduction due to re-entry of electrical circuits in the heart and a consequential conduction block
202
What is atrial fibrillation?
Quivering atria activity (no distinct P waves). Irregular ventricular contraction
203
What's a characteristic of SVT that shows on ECGs?
The P wave is 'buried in' the T wave
204
How do EADs work?
Altered ion channel activity removes the refractory period and causes depolarisation
205
How do DADs work?
Abnormal levels of Ca2+ in the SR means Ca2+ leaks out into cytosol and stimulates Na+/Ca2+ exchangers, triggering Na+ influx and depolarisation
206
Name 3 places of possible ectopic pacemaker activity
The AVN, the bundle of His, the Purkinje fibres
207
How can enhanced stimulation of the sympathetic nervous system lead to arrhythmias?
The ectopic pacemaker regions can take over
208
What causes re-entry based arrhythmia?
Different parts of the heart having refractory periods of different lengths
209
What can cause heart block?
Fibrosis or ischaemic damage to conducting pathways
210
What classifies as first degree heart block?
When the PR interval is >0.2s
211
What classifies as second degree heart block?
When more than 1 atrial impulse fails to stimulate the ventricles
212
What classifies as third degree heart block?
When the atria and ventricles beat independently of each other.
213
What's the goal of treatment of arrhythmias?
To restore sinus rhythm and normal conduction and prevent more serious and possibly fatal arrhythmia occurring
214
What do anti-arrhythmic drugs do?
Reduce conduction velocity, alter refractory periods of cardiac action potentials and reduce automaticity
215
What are class I anti-arrhythmic drugs?
Na+ channel blockers (acting in non-nodal tissue)
216
What are class II anti-arrhythmic drugs?
ß-blockers (acting at nodal and non-nodal tissue)
217
What are class III anti-arrhythmic drugs?
K+ channel blockers (acting at non-nodal tissue)
218
What are class IV anti-arrhythmic drugs?
Ca2+ channel blockers (acting at nodal and non-nodal tissue)
219
How do Class I anti-arrhythmic drugs work?
Class I drugs block Na+ channels in non-nodal tissue, such as the atria or ventricles. They block Na+ channels in their inactivated state. They only block Na+ channels in high frequency firing tissue, so the drugs are use-dependent
220
What property of class I anti-arrhythmic drugs means they don't affect normal firing?
They are fast-dissociating, so they come off the active site in time for the next impulse
221
What arrhythmias do class I drugs work for?
Very fast arrhythmias
222
How does stimulation of sympathetic nerves and activation of ß1 receptors in the heart cause pro-arrhythmic effects?
There's increased SAN and AVN firing rate, and increase in ventricular excitability by raising Ca2+ concentration
223
What do ß1 blockers such as atenolol do and when are they used?
Atenolol reduces VT after myocardial infarctions caused by increase in sympathetic nerve activity
224
How do ß blockers reduce SVT?
They slow conduction through the AVN, which reduces ventricular firing rate
225
How do class III drugs work?
Class III drugs increase the length of the action potential to increase the refractory period of the heart. They also inhibit K+ ion channels responsible for repolarisation in atria/ventricles. This is to block channels involved in repolarisation to maintain depolarisation. The Na+ channels become inactivated and cannot fire any more APs, preventing arrhythmias
226
What are class III drugs used for?
SVT and VT
227
How do class IV drugs work?
They block L-type VGCCs, which mainly affects the firing of SAN and AVN APs. Reducing Ca2+ channel activity slows down upstrokes and so less pacemaker potentials fire, decreasing heart rate
228
What 2 phases of the cardiac cycle do class IV drugs act?
Phase 0 and phase 2
229
Adenosine is an unclassified anti-arrhythmic drug. How does it work?
Adenosine decreases activity in the SAN and AVN and slows down the heart by activating K+ channels, so it's used for SVT
230
Atropine is an unclassified anti-arrhythmic. How does it work?
Atropine is a muscarinic antagonist that reduces parasympathetic activity and may be used to treat AV block and treat sinus bradycardia after MI
231
Digoxin is an unclassified anti-arrhythmic. How does it work?
Digoxin has central effects and increases vagus nerve activity, decreasing heart rate and conduction. Digoxin is a Na+/K+ ATPase blocker. It's used for AF
232
How can class III drugs end up being pro-arrhythmic?
They increase QT duration. Long QT syndrome leads to arrhythmia due to EAD and DAD generation
233
How can classes I, II and IV potentially be pro-arrhythmic?
They may increase the refractory period and reduce conduction time, which potentially can be pro-arrhythmic. Class IV may also reduce contractility.
234
What creates a need to transport solutes and fluid?
Metabolism
235
What do cell membranes consist of?
2 layers of amphipathic phospholipids
236
What are the 4 passive transport processes?
Osmosis, diffusion, convection, electrochemical flux
237
Where does solute and fluid exchange occur?
Capillaries
238
What are capillaries?
1-cell-thick, semi-permeable blood vessels with the smallest diameter
239
What properties of solutes affect transport?
Concentration gradient
Size of the solute
Lipid solubility of the solute
240
What properties of the membrane affect transport?
Membrane thickness/ composition
Aqueous pores in the membrane
Carrier-mediated transport
Active transport mechanisms
241
What is Fick's law equation for solute movement?
```
Js = -DA (∆C÷x)
D= diffusion coefficient of the solute
A= area
∆C÷x = concentration gradient across distance x
```
242
What does a negative value for solute movement mean?
The solute is moving down a concentration gradient
243
What are the 3 distinct types of capillaries?
Continuous capillaries
Fenestrated capillaries
Discontinuous capillaries
244
Describe the properties of continuous capillaries
They have moderate permeability, tight gaps between neighbouring cells and a constant basement membrane
245
Describe the properties of fenestrated capillaries
They have a high water permeability, fenestrations and modest disruption of the basement membrane
246
Describe the properties of discontinuous capillaries
They have very large fenestration structures, and a disrupted basement membrane
247
Where would you find continuous capillaries?
The blood-brain barrier
248
Where would you find fenestrated capillaries?
High water-turnover tissues such as salivary glands, kidneys and synovial joints
249
Where would you find discontinuous capillaries?
Where movement of cells is required, such as of RBCs in the liver, spleen and bone marrow
250
What are 3 other structural features of capillary walls that can influence solute transfer?
Intercellular cleft
Glycocalyx
Caveola-vesicle
251
How wide is the intracellular cleft?
10-20nm wide
252
What is the glycocalyx?
Negatively charged material that covers the outside of the endothelium and blocks solute permeation and access to transport mechanisms
253
How can the caveola-vesicle system influence solute transfer?
Large structures or proteins can be taken up by endocytosis from the vascular space, carried across and released by exocytosis into interstitial space
254
What is permeability?
The rate of solute transfer by diffusion across unit area of membrane per unit concentration difference
255
What's the equation for permeability?
```
Js= -P Am ∆C
Js= rate of solute transport
P= permeability
Am= surface area of capillary involved in transport
∆C= concentration gradient
```
256
What's glucose concentration in plasma?
1g/litre
257
What's the total volume of plasma filtrate flowing into tissues per day?
8L
258
What's the maximum filtration of glucose?
8g/day
259
What percentage of glucose transport does filtration transport account for?
2%
260
How is 98% of glucose transport carried out?
Into interstitial space via passive diffusion via GLUT transporters
261
How does increased blood flow affect solute concentration in capillaries?
Increased blood flow increases solute concentration
262
What does increased blood flow mean in the lungs?
Greater solute concentration means a steeper concentration gradient and so more O2/CO2 exchange along capillaries in the lungs
263
How does dilation of arterioles and the resulting increase in number of capillaries perfused affect diffusion?
More capillaries perfused increases total surface area for diffusion and shortens diffusion distance, leading to faster diffusion. O2 transport from blood to muscle increases by over 40 times during strenuous exercise
264
What is a thrombus?
A solid mass of blood formed within the cardiovascular system, involving the interaction of endothelial cells, platelets and the coagulation cascade, and which impedes blood flow
265
What does arterial thrombosis usually result from?
Atheroma rupture
266
What are arterial thrombi like?
Platelet-rich, white masses that block downstream arteries
267
What causes venous thrombosis?
Stasis or a hyper coagulant state
268
What are venous thrombi like?
Platelet-poor and red in colour
269
What are the 4 main components of the clotting process?
Endothelium, platelets, coagulation and fibrinolysis
270
What is normal haemostasis?
A state of equilibrium between fibrinolytic factors and anticoagulant proteins, and between coagulation factors and platelets
271
What 3 things do platelets do in primary haemostasis?
Adhere, activate and aggregate
272
What does secondary haemostasis involve?
Coagulation and the conversion of fibrinogen to fibrin
273
How does fibrinolysis occur?
A cascade whereby tissue plasminogen activator (tPA) activates plasminogen, converting it to plasmin. Plasmin then breaks down the fibrin into fragments
274
What 3 factors can govern development of a venous thrombus?
Changes in normal blood flow
Alterations in the constituents of the blood
Damage to the endothelial layer
275
What 3 things make up Virchow's triad?
Endothelial damage or dysfunction
Hypercoagulability
Stasis
276
Name some risk factors for endothelial damage or dysfunction
Smoking, hypertension, surgery, catheterisation, trauma
277
Name acquired factors for hypercoagulability
Cancer, chemotherapy, OCR/HRT, pregnancy, obesity, HIT
278
Name some hereditary factors for hypercoagulability
Factor V Leiden, Prothrombin G20210A, Protein C and S deficiency
279
Name 2 factors that can contribute to stasis of the blood
Immobility, polycythaemia
280
Briefly describe primary haemostasis
vWF binds to exposed collagen beneath damaged endothelium. Platelets bind to vWF and are activated. They express fibrinogen receptors and bind to fibrinogen, which causes platelet aggregation to form a thrombus
281
Briefly describe secondary haemostasis
Factor VIIa binds to tissue factor expressed by sub-endothelial cells, which leads to conversion of prothrombin to thrombin. Thrombin activates 2 cofactors, factor VIIIa and factor Va, which subsequently form calcium-ion-dependent complexes on the surface of platelets with factor Xa and IXa. These complexes greatly increase production of thrombin and factor Xa
282
Describe briefly the process of fibrinolysis
Once the clot is no longer needed, fibrin is broken down into smaller components (fragments). This is initiated by tPA, an endogenous fibrinolytic which sits on the surface of endothelial cells and activates plasminogen to plasmin. Plasmin is the enzyme that degrades fibrin
283
What is DIC?
Disseminated intravascular coagulation is a condition in which blood clots form throughout the body, blocking small blood vessels. This results from the proteins that control blood clotting becoming overactive
284
What can cause hypercoagulability?
Alterations in the constituents of the blood components. Decrease in fibrinolytic factors and anticoagulant proteins and increase in coagulation factors and platelets
285
What feature of veins can increase likelihood of stasis?
Valves
286
What's the annual incidence of DVT in the UK?
1 in 1000
287
Is DVT below the knee more dangerous, or DVT above the knee?
DVT above the knee is more likely to lead to pulmonary embolism
288
Name symptoms of DVT
```
Pain and tenderness of veins
Limb swelling
Superficial venous distension
Increased skin temperature
Skin discolouration
```
289
Name 2 anticoagulants
Warfarin and heparin
290
What are 'clot busters' used for?
Plasminogen activators and streptokinase can break down a clot when a patient has a massive pulmonary embolism
291
Where does fluid exchange occur?
At the capillary wall
292
What causes fluid to move across the basement membrane into interstitial space?
Hydraulic pressure from blood flow
293
Fluid movement depends on what pressures across the capillary wall?
Hydraulic pressure and oncotic pressure
294
What's the equation of Starling's principle of fluid exchange?
```
Jv = Lp A { (Pc-Pi) - sigma(πp-πi) }
Jv= net filtration
Lp= hydraulic conductance of the endothelium
A= wall area
Pc= capillary blood pressure
Pi- interstitial fluid pressure
sigma= reflection coefficient
πp= plasma proteins
πi= interstitial proteins
```
295
How is effective osmotic pressure calculated?
π x potential osmotic pressure
296
What's the value of sigma for plasma proteins?
0.9 (so only 10% get across the capillary wall)
297
What's a major problem with Starling's equation?
The glycocalyx is not taken into account
298
What are the generic structural components of the glycocalyx?
Proteoglycans and glycoproteins
299
With the glycocalyx, plasma proteins don't move into interstitial space via intercellular gaps, but via what?
Via vesicles
300
What's the revised Starling equation for fluid exchange?
Jv = Lp A { (Pc-Pi) - sigma(πp-πg)}
301
What is hypovolaemia?
Abnormally low circulating blood volume
302
What function does the lymphatic system play in blood circulation?
The lymphatic system returns excess tissue fluid/ solutes back the the cardiovascular system
303
What 3 things determine overall control of extracellular fluid balance?
Capillary filtration
Capillary reabsorption
Lymphatic system
304
What does imbalance in filtration, reabsorption, lymphatic function and glycocalyx function lead to?
Excess interstitial fluid build-up and oedema
305
Name 3 clinical causes of increased capillary pressure
Dependent oedema, DVT and cardiac failure
306
How does DVT lead to increased capillary pressure?
There's a prevention of venous return, so venous pressure is increased and causes a back-up of pressure, leading to increased Pc across capillaries and increased filtration
307
What is nephrotic syndrome?
Kidney disease characterised by oedema and loss of protein from plasma into the urine due to increased glomerular permeability
308
Why does the protein loss in nephrosis lead to oedema?
Reduced plasma protein concentration causes reduced plasma oncotic pressure (πp), so Pc has a greater influence. Fluid efflux from the capillaries into the interstitial fluid causes oedema
309
What's filariasis and how does it happen?
Filarial worms migrate to the lymphatic system and mate and multiply, then block lymphatic drainage and cause swelling
310
How can inflammation cause oedema?
Inflammation increases Lp, the hydraulic conductance of the endothelium, allowing more fluid movement and therefore build-up
311
What are the names of the 3 layers of blood vessels?
Tunica intima, tunica media and tunica adventitia
312
What's the tunica adventitia and its function?
The outer collagenous connective tissue layer that provides anchorage, support and sometimes elasticity, as well as carrying nerve supply and blood supply to the vessel
313
What is the tunica media and its function?
A smooth muscle layer for support, elasticity and contractility, allaying for physical regurgitation of blood flow and smoothing of blood flow
314
What is the tunica intima and its function?
Endothelium over a little dense connective tissue. A selectively permeable barrier to blood that regulates adhesion of leukocytes and platelets, makes mediators controlling vessel tone and makes mediators of inflammation
315
What fibres intercalate between muscle cells in the tunica media?
Elastic fibres
316
How is the tunica media different in arteries compared to in veins?
It's much thicker in arteries
317
What are the 3 types of artery?
Elastic arteries
Muscular arteries
Arterioles
318
Give examples of elastic arteries
The aorta, pulmonary arteries and their largest branches
319
What's another name for elastic arteries?
Conducting arteries
320
What's the definitive feature of elastic arteries?
They have a very thick tunica media with many elastic laminae
321
What is a dissecting aneurysm of the aorta?
Where there's a partial rupture of the arterial wall which allows blood to enter the tunica media. If tunica adventitia also ruptures, this is fatal
322
What's another name for muscular arteries?
Distributing arteries
323
Describe muscular arteries structurally
Muscular arteries have prominent internal elastic laminae between the tunica media and tunica intima. They have a thick tunica media with some elastic fibres but no elastic laminae. The adventitia is mainly collagen
324
What is different about the elastic laminae in elastic arteries and muscular arteries?
elastic arteries have many elastic laminae in the tunica media, whereas muscular arteries have a single internal and external lamina
325
What classifies as an arteriole?
A microscopic artery of <0.3mm in diameter
326
What is the predominant layer in arterioles and why?
The tunica media is predominant for contractility against high BP
327
What direction does the smooth muscle in arterioles run?
Circularly
328
What are capillaries?
Blood vessels specialised for exchange between blood and tissues, made only of endothelium with scattered pericytes
329
What limits exchange and allows regulation in capillaries?
The thin layer of endothelial cytoplasm lining the capillary lumen
330
What are sinusoids?
Wider fenestrated capillaries found in the liver and spleen, which allow slow blood flow and the highest rate of exchange
331
What's the function of veins and venules?
These vessels are specialised to return low-pressure blood to the heart
332
Describe the histology of veins
Venis have relatively thin, flexible walls, often with prominent adventitia. The media is relatively thin, but still controls flow and pressure
333
What may some major veins have in their walls?
Longitudinal smooth muscle to assist flow against gravity
334
What do the atria secrete to regulate blood pressure?
ANP (atrial natriuretic peptide)
335
When do the atria release atrial natriuretic peptide from granules?
When the atria stretch after being filled with blood
336
What does ANP do?
ANP increases secretion of water and Na+ into urine, resulting in reduction or buffering of blood pressure
337
What are the 3 layers of the heart?
Epicardium, myocardium, endocardium
338
What's the epicardium?
The outer layer of fatty, loose connective tissue with nerves, blood vessels and smooth, lubricated epithelial covering (mesothelium)
339
What's the myocardium?
The middle layer of cardiac muscle, which contracts to give heart beats
340
What's the endocardium?
A thin layer of endothelium and some loose connective tissue
341
What separates the intima and media of blood vessels?
A fenestrated internal elastic lamina
342
What separates the media and adventitia of blood vessels?
An external elastic lamina
343
What does vascular tone describe?
The degree of constriction of a blood vessel relative to maximum dilation
344
What controls vascular tone?
The contractile state of vascular smooth muscle cells
345
Do capillaries have vascular tone?
No, as they have no VSMCs
346
What regulates vascular tone?
Constrictor responses and dilator responses
347
What are intrinsic local controls needed for?
Regulating local blood flow to organs/tissues
348
What are extrinsic controls useful for?
Regulating TPR to control blood pressure, as blood pressure is the drive for blood flow
349
What are the nervous extrinsic controls?
Vasoconstrictors such as noradrenaline and vasodilators such as Ach and NO
350
What are the hormonal extrinsic controls?
Vasoconstrictors- adrenaline, angiotensin II and vasopressin, and vasodilators- ANP
351
What's the most important extrinsic control of circulation?
The sympathetic vasoconstrictor system
352
What do the receptors at postsynaptic membranes of sympathetic vasoconstrictor nerves do?
a1-adrenoreceptors: contraction
a2-adrenoreceptors: contraction
ß2-adrenoreceptors: relaxation
353
What's the purpose of a2-adrenoreceptors on the presynaptic membrane?
Excess NA in the synaptic cleft binds to presynaptic a2 receptors to trigger negative feedback and uptake NA back into presynaptic vesicles to be stored
354
What's the effect of Angiotensin I feeding back onto the presynaptic membrane?
NA release is increased and RAAS increases sympathetic activity
355
What's the effect of K+ and adenosine feeding back onto the presynaptic membrane?
They reduce the release of NA in a vasodilatory pathway
356
What controls the sympathetic vasoconstrictor nerves?
The brainstem RVLM (rostral ventrolateral medulla)- the vasomotor centre
357
What receptors does NA act at on vascular smooth muscle cells?
a1-adrenoreceptors
358
What is meant by the fact that sympathetic nerve activity is tonic?
Action potential fire at around 1/second
359
What's the role of sympathetic vasoconstrictor nerves?
Produce vascular tone and allow vasodilation and increased blood flow
360
Give an example of when some vessels vasoconstrictor and others vasodilator simultaneously
During exercise, sympathetic innervation to the GI tract is increased to decrease blood flow, while sympathetic innervation to the skin is decreased to increase blood flow and cool the skin down
361
How is precapillary vasoconstriction important in hypovolaemia?
Precapillary vasoconstriction decreases capillary pressure due to pressure drop, increasing absorption of interstitial fluid into blood plasma to maintain blood volume
362
How do sympathetic vasoconstrictor nerves control venous blood volume?
Venoconstriction decreases venous blood volume by increasing venous return as it increases stroke volume via Starling's law
363
What are the vasoconstrictor hormones acting on VSMCs?
Adrenaline, angiotensin II and ADH
364
What is the vasodilator hormone acting at VSMCs?
ANP
365
How can VSMC-controlling hormones become pathological?
If they're produced in excess, they can cause excessive vasoconstriction and vascular disease such as hypertension and heart failure
366
When and where is adrenaline released and what receptors does it act on?
Adrenaline is released mainly from the adrenal glands due to sympathetic nerve stimulation. It acts on a1-adrenoreceptors on VSMCs
367
How is angiotensin II formed and where does it act?
It's formed from the RAAS and acts on AT1 receptors on VSMCs
368
Name 2 other important vasoconstrictors besides adrenaline and Ang II
Endothelin-1 and thromboxane
369
Where's endothelin-1 released and where does it act?
ET1 is released from the endothelium to act on ETA receptors on VSMCs
370
Where's thromboxane released and where does it act?
TXA2 is released from aggregating platelets to act on TP receptors on VSMCs
371
Describe briefly the process of the RAAS system
Renin secreted by the kidney acts on angiontensinogen to release angiotensin I. 10-amino-acid Ang I is then cleaved by angiotensin-converting enzyme (ACE) into the octapeptide angiotensin II. As well as causing vasoconstriction, Ang II increases secretion of cortisol and aldosterone by a direct action on the adrenal cortex
372
Stimulation of what receptors causes renin release from granular cells?
ß1-receptors
373
Where does ANP act?
ANP acts at NP receptors on VSMCs
374
What does ANP stimulate?
Increase in the cGMP pathway
375
How does ANP reduce blood pressure?
Systemic vasodilation, which opposes the actions of Na, Adr, Ang II, ADH, ET-1 and TXA2
376
What effect does ANP have on renal afferent arterioles?
ANP dilates renal afferent arterioles, increasing glomerular filtration rate and Na+ and H2O excretion by the kidney. This decreases blood volume
377
What hormones does ANP decrease release and action of?
Aldosterone, renin and ADH, so as to increase glomerular filtration
378
What is a necrotic core made up of?
Lipid, cholesterol clefts, fibrin, foam cell remnants and cell debris
379
What are foam cells?
A type of macrophage which localise fatty acid deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance
380
What are the 2 types of foam cell?
One is considered a modified smooth muscle cell derived from cells of the arterial tunica media. The other is a macrophage of reticuloendothelial origin (probably a blood monocyte)
381
What's the relationship between foam cells and the necrotic core in an atheromatic plaque?
Foam cells surround the necrotic core
382
What type of factors can contribute to atherosclerosis?
Angiogenic factors that induce neovascularisation at the base of the plaque
383
What's the fibrous cap made of?
Predominantly made of collagen intertwined with smooth muscle in dynamic equilibrium
384
How does atherosclerosis begin?
As an initial lesion which is isolated from cells. A fatty streak can then form from intracellular lipid accumulation.
385
What happens after formation of a fatty streak in the development of atherosclerosis?
Intermediate lesions ensue and the next step is an atheroma. Once fibrotic/ calcific layers develop, the atheroma is considered a fibroatheroma, which can have a single, or multiple, lipid cores.
386
Where are the most common sites of plaque build up?
The circle of Willis, carotid arteries, coronary arteries, the aorta or iliac arteries
387
Name some major risk factors for atherosclerosis (12 total)
```
Age
Male sex
Genetics
Hyperlipidaemia
Smoking
Hypertension
Diabetes mellitus
Obesity
Metabolic syndrome
Alcohol
Drugs
Systemic inflammation
```
388
What's an important property of LDL?
LDL is an inflammatory mediator, so it can induce cytokine production from other cells
389
What's the initiation stage of the mechanism of plaque development?
A mediator such as oxidised LDL or angiotensin II activates endothelial cells to become dysfunctional. When this happens, the endothelial cells begin secreting cytokines and adhesion molecules, which cause circulating monocytes to stick to the adhesion molecules on the surface of the endothelial cells and then penetrate the endothelial layer to move into the intima (diapedesis)
390
What is diapedesis?
The passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation
391
What happens in the plaque development process after the monocytes have moved into the intima?
The monocytes then differentiate into tissue macrophages and can secrete other cytokines. The macrophage can then incorporate more LDL and uptake LDL to become foam cells. The increased expression of cytokines by the macrophage causes activation of smooth muscle cells within the lining of the media to migrate into the intima when they start to proliferate
392
What can smooth muscle do in the initiation of plaque development after they migrate into the intima?
They can shift from a contractile phenotype to a proliferative phenotype (a synthetic phenotype) which synthesises matrix proteins. This change is caused by an alteration in the gene expression of the smooth muscle cells. The cells can then secrete extracellular matrix components such as collagen and elastin as well as proliferating by division. The smooth muscle cells can also become foam cells by up taking LDL
393
What happens when foam cells apoptose?
The LDL accumulates to form a lipid core. The collagen secreted by smooth muscle cells begins to form a fibrous plaque in the intima. Calcium can also be secreted from foam cells to be deposited into the intima and to calcify the fibrous plaque
394
What can an atheroma lead to?
Occlusive thrombosis (e.g. myocardial infarction), thromboembolism (e.g. ischaemic stroke), peripheral vascular disease (e.g. critical limb ischaemia) or aneurysm due to wall weakness (e.g. aortic aneurysm)
395
What does an infarction involve?
Obstruction of blood flow to an organ or region of tissue, causing local tissue death
396
What is an indicator of cardiac necrosis?
Elevated cardiac troponins e.g. cTnT
397
What surgical intervention treatment is there for myocardial infarction?
Balloon angioplasty, stenting and coronary bypass
398
What are used in therapeutic thrombolysis for myocardial infarction?
tPA and a bacterial activator (streptokinase)
399
When are D-dimers generated?
When cross-linked fibrin is degraded.
400
When is FDP generated?
Fibrin degradation products are generated if non-cross-linked fibrin or fibrinogen is broken down
401
What are possible complications of MI? (5)
Acute pump failure, conduction problems (arrhythmia), valve dysfunction, stroke or chronic pump failure
402
What is vascular tone produced by sympathetic vasoconstrictor nerves inhibited by?
Parasympathetic vasodilator nerves, sympathetic vasodilator nerves and sensory (nociceptor C fibre) vasodilator nerves
403
Where in the body do parasympathetic nerves innervate blood vessels?
In salivary glands, the pancreas and intestinal mucosa, as well as male genitalia
404
What neurotransmitters are released from parasympathetic nerves that innervate blood vessels?
Ach/VIP are released in the salivary glands, while only VIP is released in the pancreas and intestinal mucosa
405
Why do the tissues with blood vessels innervated by parasympathetic nerves need high blood flow?
To maintain parasympathetic-mediated fluid secretion
406
What do Ach and VIP released from parasympathetic nerves innervating blood vessels do?
They act on endothelium to cause release of NO and stimulation of vasodilation to increase blood flow to produce more saliva or digestive enzymes
407
Describe how the parasympathetic innervation to the blood vessels in the male genitalia work
They release NO, causing production of cGMP, which leads to vasodilation.
408
How does Sildenafil (viagra) work?
Sildenafil enhances the effects of NO by blocking the breakdown of cGMP by phosphodiesterase 5
409
How do sympathetic vasodilator nerves in the skin work?
Sudomotor fibres release Ach/VIP for vasodilation associated with sympathetic-mediated sweating.
410
How do sensory vasodilator fibres work?
When trauma stimulates nociceptor C fibres, impulses fire towards dorsal root ganglia in the spinal cord to eventually be perceived as pain. Axon collaterals are also stimulated. Either the impulse down the axon collateral will stimulate release of neurotransmitter (Sub P) to cause vasodilation, or to activate mast cells to release their granule content, and histamine will cause vasodilation. The skin 'flares up'
411
What is shear stress?
The tangential force of the flowing blood on the endothelial surface of the blood vessel
412
What does high shear stress promote?
High shear stress, as found in laminar flow, promotes endothelial cell survival and quiescence, alignment in the direction of flow, and secretion of substances that promote vasodilation and anticoagulation
413
What detects shear stress and what effect occurs on detection?
Shear stress can be detected by receptors on the endothelial surface, and this causes production of nitric oxide because it stimulates endothelium nitric oxide synthase (eNOS). eNOS causes production of nitric oxide via an amino acid called arginine
414
Describe nitric oxide
Nitric oxide, made in large concentrations in the endothelial cells, is a very lipophilic, soluble gas which is freely diffusible and stimulates guanylate cyclase (GC) in vascular smooth muscle cells.
415
What does GC do?
GC activates cGMP, which activates PKG
416
What controls vascular tone?
Tonic sympathetic activity (constriction) and tonic NO release (dilation) in combination. Vascular tone is a balance between the two
417
Where does NO get released in the circulatory system?
NO release occurs almost throughout the circulatory system
418
What effect does shear stress have in the kidney?
It causes the production of prostacyclin, as specific membrane lipid are converted into prostacyclin by cyclooxygenase (COX). PGI2 is released, which acts on prostanoid receptors on VSMCs, activating the A pathway and causing vasodilation. This is needed to maintain blood flow in renal arterioles and maintain GFR
419
Why shouldn't you give someone with renal failure COX inhibitors or NSAIDs?
Because this process involving prostacyclin is very important to kidneys to keep blood flowing to via renal arteries. A drug that blocks COX decreases PGI2 production, the A pathway and vasodilation, so a drop in renal blood flow can be dangerous
420
Via what 3 things do the G pathway and the A pathway cause vasodilation?
1) They increase Ca2+ ATPase activity, increasing uptake of Ca2+ into the SR stores and exclusion of Ca2+ from the cell, keeping Ca2+ concentration low to produce less contraction
2) They increase K+ channel activity, so K+ channels open and K+ moves out of the cell, causing hyperpolarisation and switching off VGCCs. This means less Ca2+ uptake
3) They decrease myosin light-chain kinase activity
421
How does activation of K+ channels lead to vasodilation?
Activation of K+ channels in the endothelium means the release of K+ and rise in local external K+ levels. The potassium activates process on the VSMCs to switch on K+ channels and increase Na2+/K+ ATPase activity. These both lead to hyper polarisation of VSMCs, decrease in VGCC activity and Ca2+ entry, therefore contributing to vasodilation
422
Where is the hyper polarisation from K+ channel activation conducted?
The hyper polarisation can be conducted from the endothelium to VSMCs via a gap junction (low resistance pathway). This then decreases VGCC activity and Ca2+ entry, causing vasodilation
423
Stimulation of what receptors on VSMCs produces vasodilation in coronary and skeletal muscle arterioles?
ß2-adrenoreceptors
424
What does ß2-receptor stimulation increase?
PKA activity
425
What 3 changes occur when PKA activity increases?
1) Increase in Ca2+ ATPase activity, lowering Ca2+ concentration inside the VSMC
2) Increase in K+ channel activity, leading to hyper polarisation and consequential decrease in VGCC
3) Decreased MLCK activity
426
Besides vascular tone, what are the functions of endothelium?
```
Production of Ang II
Blood clotting
Inflammatory pathways
Angiogenesis
Atheroma
```
427
How does endothelium dysfunction affect vascular tone?
The effect is profound. NO and PGI2 production is reduced, so vasoconstriction is enhanced. This is why ED is linked to many CVDs
428
What is the defining level to indicate hypotension?
Systolic blood pressure below 60 mmHg
429
What's Darcy's law?
Blood flow= blood pressure ÷ TPR
430
What does vascular tone mean?
It describes the degree of constriction of a blood vessel relative to the maximum dilation.
431
What controls vascular tone?
Regulation of vascular smooth muscle cells and endothelium
432
How does sepsis lead to no drive for end organ perfusion?
Systemic infection causes excessive vasodilation, which decreases TPR and BP
433
Why does anaphylaxis lead to poor end organ perfusion?
The hypersensitivity reaction involves systemic vasodilation
434
How does heart failure cause poor end organ perfusion?
Poor cardiac output means blood pressure's low, which means poor end organ perfusion
435
Why do adrenaline have different responses on resistance vessels?
Adrenaline has a higher affinity for ß-adrenoreceptors over alpha-adrenoreceptors, while noradrenaline has a higher affinity for alpha-adrenoreceptors. Alpha1-receptors produce contraction, so noradrenaline acts at a1-receptors to cause vasoconstriction. ß2-receptors produce relaxation, so adrenaline causes vasodilation
436
As a general principle, when would you give noradrenaline?
To increase blood pressure whilst protecting the heart
437
Asa. general principle, when would you give adrenaline?
To increase heart activity and cause a small increase in blood pressure due to vasodilation
438
Why's noradrenaline given and how does it work?
Noradrenaline is given to primarily act at a1-adrenoreceptors on VSMCs to increase TPR and increase blood pressure without having significant effects on the heart (ß1), so it's cardiac protective- doesn't make the heart work hard to increase BP and blood flow
439
Why is the cardiac protective nature of NORAD important?
It means NORAD can be given to patients with sepsis and severe heart failure
440
Why is adrenaline given and how des it work? Give an example of its use
Adrenaline is given in high concentrations to have an action on both ß1-receptors on the heart and alpha1-receptors on VSMCs to raise BP. An example of a use of adrenaline is in an epipen for anaphylaxis
441
What is raised blood pressure a cause of, which reduces important tonic vasodilation processes and causes poor end organ perfusion?
Endothelium dysfunction
442
What does hypertension increase? What effect does this increase have?
Afterload
| Cardiac output becomes poor and the heart must work much harder
443
What do angiotensin II receptor (AT1) antagonists (ARBs) do?
They block AT1 receptors to reduce vasoconstriction in heart failure or hypertension
444
Name an ARB
Losartan
445
What do angiotensin converting enzyme inhibitors (ACEi's) do?
They reduce Ang II levels for treatment of heart failure and hypertension
446
Name an ACEi
Enalapril
447
What do alpha1-adrenoreceptor antagonists do?
They are competitive receptor antagonists for treatment of drug-resistant hypertension
448
Name an alpha1-adrenoreceptor antagonist
Prazosin
449
What do ETA receptor antagonists do?
They block ETA receptors which are unregulated in pulmonary artery hypertension
450
Name an ETA receptor antagonist
Bosetan
451
What do vascular selective CCBs do? Name the vascular selective subtype
Dihydropyridine subtypes are vascular selective and block influx of Ca2+ to reduce vasoconstriction for hypertension and angina
452
Name a dihydropyridine CCB
Amlodipine
453
What do K+ channel openers do?
They open K+ channels to cause hyper polarisation, so there's less VGCC activation and Ca2+ influx, leading to vasodilation to treat angina
454
Name a K+ channel opener
Nicorandil
455
How do nitrates work?
They are NO donors, causing PKG-mediated vasorelaxation for treatment of angina and pulmonary oedema
456
Name a nitrate
GTN spray (glyceryl trinitrate)
457
How doe PDE5 inhibitors work?
They decrease cGMP breakdown, allowing PKG-mediated vasodilation to treat erectile dysfunction
458
Name a PDE5 inhibitor
Sildenafil (viagra)
459
Why is a D-dimer test done?
D-dimer is an indicator of clot formation because it's a degradation product of cross-linked fibrin
460
Can D-dimer tests be used to 'rule-out' DVT?
Only in combination with clinical evaluation
461
What is rivaroxaban?
A direct FXa inhibitor- an anticoagulant (blood thinner) which reduces the likelihood of blood clots
462
What are primary and secondary prevention of disease?
Primary prevention lowers the risk of the disease occurring. Secondary prevention lowers the risk of disease recurring
463
Name the modifiable risk factors for CVD
```
Smoking
Abnormal lipid profile
Hypertension
Diabetes mellitus
Abdominal obesity
Psychosocial factors like stress
```
464
What are protective factors for CVD
Regular fruit and vegetables in the diet
Exercise
Moderated alcohol consumption
465
What are the non-modifiable risks for CVD?
Age
Family history
Ethnicity
466
What's the individiual response to primary prevention?
A clinician tailors care to an individual patient's needs and risk factors
467
Give an example of a secondary prevention measure for CVD
Prescribing statins after a CHD event
468
How much does CVD cost UK healthcare and the UK economy per year?
£9 billion for the NHS and @19 billion for the economy
469
What is cardiovascular disease an umbrella term for?
CHD, venous thromboembolism, cerebrovascular disease, peripheral arterial disease, rheumatic and congenital heart disease and lymphatic disease
470
How does risk of stroke change after the age of 55?
Risk of stroke doubles every decade after the age of 55
471
How is risk of CVD increase if a direct blood relative had a stroke?
Risk is increased if a male relative had a stroke before 55 or if a female relative had a stroke before 65
472
How does ethnicity affect risk of CVD?
People from Pakistan, Bangladesh, India and Afro-Caribbean countries are more prone to CVD
473
What are 2 special requirements of cutaneous circulation?
It must defend the body against the environment.
| It's important to regulation of body temperature
474
How is cutaneous circulation important to temperature regulation?
Blood flow delivers heat from the body's core, and temperature is regulated via radiation, conduction, convection and sweating
475
What temperatures can skin be at for short periods of time without getting damaged?
0° to 40°
476
What does skin temperature depend on?
Skin blood flow and ambient temperature
477
What's a special structural feature of cutaneous circulation?
Artery-venous anastomoses- direct connections of arterioles to venules that expose blood to regions of high surface area
478
What are arterioles controlled by?
Sympathetic vasoconstrictor and sudomotor vasodilator fibres driven by temperature regulation nerves in the hypothalamus
479
What do Sudomotor fibres do as well as vasodilation?
They induce sweating to Coll the body down
480
Name 3 special functional features of cutaneous circulation
The skin is responsive to ambient and core temperatures
Severe cold causes 'paradoxical cold vasodilation' to prevent skin damage.
Core temperature will change the responses of hypothalamic neurones which control sympathetic activity
481
How does increase in ambient temperature trigger response from cutaneous circulation?
The higher ambient temperature triggers vasodilation and ventilation, which help heat loss
482
How does decrease in ambient temperature trigger response from cutaneous circulation?
The lower ambient temperature causes vasoconstriction and venoconstriction, which helps to conserve heat. Cold-induced vasoconstriction is caused by an abundance of a2-adrenoreceptors on VSMCs in the skin and decrease in the A pathway. a2-receptors bind NA at lower temperatures than a1-receptors
483
What causes paradoxical cold vasodilation?
Paralysis of the sympathetic transmission
484
How does detection of increase in core temperature lead to decrease in body temperature?
Increase in core temperature stimulates warmth receptors in the anterior hypothalamus, causing sweating (increased sympathetic activity to sweat glands) and vasodilation (increased sympathetic Sudomotor activity to arterioles in extremities)
485
How does baroreflex/RAAS/ADH-stimulated vasoconstriction of skin blood vessels work?
Following decreased BP due to haemorrhage, sepsis or acute cardiac failure, blood is directed to more important organs/tissues. Sympathetic vasoconstrictor fibres are stimulated and more adrenaline is secreted from adrenal glands, increasing sympathetic activity. This leads to more Ang II production and vasopressin secretion. All these factors combine to cause vasoconstriction
486
What will the skin of the patient going through response to haemorrhage be like?
Pale and cold
487
Why can it be dangerous for the body to warm up too quickly during haemorrhage?
If the body warms up too quickly, cutaneous vasoconstriction will be reduced and blood will flow to the skin and not so much to vital organs/ tissues
488
What's another specialisation of cutaneous circulation?
Blushing shows emotion. It involves sympathetic Sudomotor fibres
489
What's the Lewis triple response to skin injury?
Local redness at the site of trauma
Local swelling- inflammatory oedema
Spreading flare- vasodilation spreading out from the site of trauma
490
What's the point of the vasodilation involved in the Lewis triple response?
Vasodilation increases delivery of immune cells and antibodies to the site of damage to deal with invading pathogens
491
How does the C fibre axon reflex mediate the flare in response to trauma?
Trauma stimulates nociceptive C fibres, which causes pain sensation, but also sends impulses down axon collaterals, which causes 2 effects. Firstly, substance P is released, and secondly, mast cells degranulate to release histamine. These 2 substances cause vasodilation. They also increase the permeability of capillaries, so there's more filtration and therefore local swelling
492
What are 3 special problems of cutaneous circulation?
Prolonged obstruction of flow by compression
Postural hypertension/ oedema due to gravity
Raynaud's disease
493
What can prolonged obstruction of flow by compression lead to?
Severe tissue necrosis
494
Where are the common places for bed sores?
Heels, buttocks and weight-bearing areas
495
How can bed sores be avoided?
Shifting position or turning, causing reactive hyperaemia on removal of compression. The skin has high tolerance to ischaemia
496
How does postural hypertension and oedema due to gravity come about?
Standing up for long periods in hot weather will decrease CVP (hypotension) and increase capillary permeability, leading to oedema in the fingers or ankles. Symptoms are faintness and tightening of rings on fingers
497
What's Raynaud's disease?
Sustained vasoconstriction when your hands get really cold, so there's no paradoxical vasodilation. This leads to localised tissue ischaemia and numbness
498
What are 2 special requirements of pulmonary circulation?
Gaseous exchange
| Area for metabolic function
499
How's the pulmonary circulation adapted for gaseous exchange?
The lungs receive the entire cardiac output from the right ventricle. A low-pressure system is needed to get all the blood through.
500
Why is the pulmonary circulation an excellent system to produce or remove substances?
Because the lungs receive the entire CO from the RV
501
What are the 2 special structural features of pulmonary circulation?
Very high capillary density
| Very short diffusion distance between capillaries and alveoli
502
What's the importance of the very short diffusion distance between capillaries and alveoli?
The very short diffusion distance allows for rapid diffusion
503
What do the structural features together provide?
Huge oxygen diffusion capacity
504
What are the 3 special functional features of pulmonary circulation?
Low vascular resistance
Hypoxia pulmonary vasoconstriction
Metabolic functions
505
How does hypoxia pulmonary vasoconstriction work?
In systemic circulation, a drop in O2 levels leads to vasodilation, termed metabolic hyperaemia. Hypoxia that's not in pulmonary circulation causes vasoconstriction. Vasoconstriction prevents blood flow to poorly ventilated regions of the lungs, optimising ventilation:perfusion ratio. Hypoxia does this by increasing excitability and contractility of vascular smooth muscle
506
Why do pulmonary vessels contain ACE?
To produce Ang II and remove bradykinin/5-HT/NA
507
What are the 3 special problems with pulmonary circulation?
Gravity
Chronic HPV
Pulmonary oedema
508
What problem does gravity pose to pulmonary circulation?
In an upright position, the pulmonary arterial pressures at the apex of the lung are low due to gravity. Mean pulmonary artery (MPA) pressure is 15mmHg, while pressure in the apex is 3mmHg and in the base it's 21mmHg. Poor perfusion at the apex leads to vessel collapse. Therefore, a standing person has slightly impaired blood oxygenation
509
What happens when you're at high altitude for long periods of time, or you have COPD?
You're hypoxic, leading to vasoconstriction, pulmonary hypertension and right ventricular failure
510
Why is pulmonary oedema a problem?
Thinness of capillary-alveoli interactions means there's potential for stress and leakage due to breakdown those junctions, e.g. in mitral valve stenosis. Increased pressure in the left atrium leads to increased pulmonary capillary pressures, increased filtration and oedema.
511
What are 2 special requirements of skeletal muscle circulation?
Exercise
| Controlling arterial pressure
512
Why can vasodilation and vasoconstriction of skeletal muscle circulation have profound effects on blood pressure?
Skeletal muscle makes up 40% of body mass, so vascular resistance is a major contributor to TPR
513
What's the special structural feature of skeletal muscle circulation?
Capillary density differs in different muscles
514
How does capillary density between muscles?
Postural muscles such as soles are always active, so they have a higher capillary density than phasic muscles such as forearm muscles or gastrocnemius. Endurance training increases capillary growth at a rate proportional to numbers of mitochondria per fibre
515
What are 4 special functional features of skeletal muscle circulation?
High vascular tone
Metabolic vasodilation
High expression of ß2-adrenoreceptors on VSM
O2 extraction
516
Why is vascular tone of skeletal muscle circulation high?
This reduces blood flow at rest, enabling significant vasodilation to occur during exercise to increase blood flow. Also, it reduces blood flow to capillaries at rest, switching them off. During vasodilation, capillary recruitment further increases blood flow and increases surface area for gaseous exchange
517
How does metabolic vasodilation relate exercise intensity to increased blood flow?
Metabolic products- K+, adenosine, PO4 3-, and H2O2- produce vasodilation
518
What's the importance of having lots of ß2-adrenoeceptors on VSM?
Stimulation of ß2-adrenoreceptors by adrenaline leads to vasodilation, increasing blood flow to the skeletal muscle that we're using for exercise. Importantly, this has a huge effect on TPR. TPR is reduced so we don't produce high blood pressure during exercise, which would impede function of the heart
519
How does O2 extraction change during exercise?
O2 extraction is increased from 25-30% to 80-90% during high intensity exercise due to increased blood flow, increased area for exchange (capillary recruitment), reduced distance for exchange and muscle cells using lots more O2
520
What are 3 special problems with skeletal muscle circulation?
Mechanical interference
Increased capillary pressure during exercise
Leg arteries are a major area for atheroma
521
What is the problem of mechanical interference for skeletal muscle circulation?
When muscles contract, blood flow in intra-muscular vessels is reduced. This is OK when you're doing rhythmic exercise, however, in sustained contraction (carrying something), the reduced blood flow means poor O2 supply, anaerobic respiration, build-up of lactic acid and muscle fatigue. The body tries to force blood through the contracted muscle by increasing blood pressure
522
What's the problem with increased capillary pressure during exercise?
Increased capillary pressure leads to increased filtration of plasma into muscles and oedema. Plasma volume is reduced by around 10% during exercise
523
What causes heart failure?
The inability of the heart to supply sufficient blood flow to meet the body's needs
524
What's class I of the NYHA functional classification of heart failure?
No limitations. Ordinary physical activity does not cause fatigue, breathlessness or palpitation.
525
What's class II heart failure?
Slight limitation of physical activity. Such patients are comfortable at rest. Ordinary physical activity results in mild fatigue, palpitation, breathlessness or angina pectoris
526
What's class III heart failure?
Marked limitation of physical activity. Although patients are comfortable at rest, less than ordinary physical activity will lead to symptoms
527
What is class IV heart failure?
Inability to carry on any physical activity without discomfort. Symptoms of congestive cardiac failure are present, even at rest. With any physical activity increased discomfort is experienced
528
What's the prevalence of heart failure and how does this change in those above 65 years of age?
Prevalence is about 1-2%, although it rises to 6-10% in people over 65
529
What are 5 compensatory mechanisms for heart failure?
```
Ventricular dilation
Inccreased myocardial contractility
Myocardial hypertrophy
Sympathetic stimulation
Renin-angiotensin-aldosterone system
```
530
What's the Frank-Starling law and how is it affected in heart failure?
Increased ventricular filling of the ventricle results in increased force of contraction. In heart failure, this mechanism fails, as the ventricle is over-stretched, reducing ability to cross-link actin and myosin filaments
531
What deleterious effect does continuous sympathetic activation give?
The continuous sympathetic activation leads to ß-adrenergic down regulation and desensitisation, so there's less inotropic response
532
What negative results can increased heart rate have as a compensatory mechanism to heart failure?
Increased heart rate leads to increased metabolic demands and myocardial cell death
533
What's the deleterious effect of increased preload in heart failure?
Increased preload beyond the limits of Starling's law means pressure is transmitted to pulmonary vasculature, leading to pulmonary oedema
534
What deleterious effect does increased TPR have as a compensatory mechanism during heart failure?
Increased TPR means higher afterload leading to decreased stroke volume and carried output
535
What's bad about continuous neurohumoral activation as a compensatory mechanism for heart failure?
Chronically elevated angiotensin-II and aldosterone triggers production of cytokines, which stimulate macrophages and stimulate fibroblasts, resulting in myocardial remodelling, which leads to loss of contractility
536
What's the points of ventricular dilation in heart failure?
The ventricle dilates to maintain SV.
537
What happens when ventricular dilation becomes exhausted?
When this compensatory mechanism is exhausted, the pressure in the stretched ventricle steadily increases, resulting in restriction to filling and increased venous pressures
538
What do beta blockers do?
They decrease blood pressure (after load) decrease heart rate and decrease contractility
539
What detects decrease in perfusion pressure?
Baroreceptors in the carotid sinus and aortic arch
540
What does central and peripheral chemoreflex activation induce?
Adrenaline, noradrenaline and vasopressin release. This results in increased heart rate and contractility plus peripheral vasoconstriction
541
What effect do ACEi's and ARBs have on the heart?
They lead to decreased SVR (after load) and decrease in venous pressure (preload) by decreased Na+ and H2O retention.Myocyte damage occurs via myocyte fibrosis and eccentric ventricular hypertrophy
542
What are 3 clinical signs of heart failure?
```
Peripheral oedema (right heart failure)
Pulmonary oedema (left heart failure)
Congestive cardiac failure (left and secondary right ventricular failure)
```
543
What are 5 mechanical causes of pump failure?
```
Impaired ventricular function`
Pressure overload of the ventricle
Inflow obstruction of the ventricle
Valvular disease
Volume overload of the ventricle
```
544
What conditions cause impaired ventricular function?
Myocardial infarction or cardiomyopathy
545
What conditions cause pressure overload of the ventricle?
Systemic or pulmonary hypertension
546
What conditions cause inflow obstruction to the ventricle?
Restrictive cardiomyopathy, diastolic heart failure or mitral stenosis
547
What conditions cause valvular disease?
Aortic, mitral or tricuspid stenosis/ regurgitation
548
What conditions cause volume overload of the ventricle?
Ventricular and atrial septal defects
549
What are clinical signs of right ventricular failure?
Increased JVP, oedema and right>left pleural effusion
550
What is the clinical sign for left ventricular failure?
Pulmonary oedema
551
What are the symptoms of pulmonary oedema from left ventricular failure?
Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea
Renal dysfunction from low perfusion pressure and high venous pressure
Iron deficiency
Gout
Cardiac cachexia and skeletal muscle wasting
552
What's the most common cause of left ventricular failure?
CAD
553
What's a biomarker of heart failure?
NTproBNP
554
What's the pitfall with NTproBNP tests?
They aren't specific and NTproBNP is often mildly raised in other conditions like atrial fibrillation and hypertension. If elevated and heart failure is suspected, an echo must be requested
555
What are the treatment options for heart failure?
```
Biventricular pacing
Cardiac resynchronisation therapy
Heart transplant
Left ventricular assist devices
Palliative care
```
556
What's the requirement of coronary circulation?
It needs a high basal supply of O2 (20x that of resting skeletal muscle)
557
What's the importance of high capillary density in cardiac muscle?
It provides a large surface area for O2 transfer and reduces diffusion distance to the myocytes and so O2 transport is much faster
558
What allows/ causes a lot of resting vasodilation in coronary vessels?
High blood flow is facilitated by sparse sympathetic-mediated vasoconstriction and high NO release
559
What makes further increase in coronary blood flow during increased demand possible?
Metabolic hyperaemia and the abundance of ß2-adrenoreceptors to which adrenaline can bind
560
What level is O2 extraction at in cardiac muscle during normal activity?
75%
561
How can O2 demands be met during increased demand?
Blood flow must be increased. Myocardium metabolism generates metabolites to produce vasodilation and increase blood flow- metabolic hyperaemia
562
When does coronary blood flow occur?
During diastole
563
Why does decreased perfusion produce major problems in coronary arteries?
Coronary arteries are functional end-arteries
564
What can cause sudden obstruction of coronary blood flow?
Acute thrombosis or acute coronary syndrome (ACS)
565
What can cause slow obstruction of coronary blood flow?
Atheroma causing narrowing of lumens, which produces angina
566
What 3 mechanical factors reduce coronary flow during diastole?
Shortening diastole e.g. high heart rate
Increased ventricular end-diastolic pressure e.g. volume-overload heart failure
Reduced diastolic arterial pressure e.g. hypotension/aortic regurgitation
567
Why can't coronary blood flow be diverted to ischaemic areas?
There are low numbers of cross-branching collateral vessels (artery-arterial anastomoses)
568
What does total occlusion of the left anterior descending artery lead to?
A large ischaemic area and myocardial infarction. Ischaemic tissue causes acidosis and pain due to stimulation of C-fibres, impaired contractility, sympathetic activation, arrhythmias and necrosis
569
What is angina pectoris?
Strangulation of the chest- A painful, crushing sensation in the chest which radiates to the neck, arms and jaw and is associated with shortness of breath and dizziness.
570
What are the 3 forms of angina?
Stable, variant and unstable
571
What causes angina?
Ischaemia from O2 and nutrient demands of cardiac tissue not being met, due to partial occlusion of coronary arteries
572
What might be the reason for the increased demand?
Increased heart rate, increased left ventricular contractility or increased wall stress
573
What triggers increase in demand for O2 or nutrients?
Exercise, hypertension and left ventricular dilation
574
How does resistance in healthy coronary arteries work at rest and during exercise?
In healthy individuals, resistance in series adds together in coronary arteries. In exercise, metabolic vasodilation of arterioles reduces total resistance. Blood flow is increased to meet increased O2 demands
575
What happens to resistance in coronary arteries of someone with stable angina?
Individuals with stenosis in large coronary arteries have increased resistance. Metabolic hyperaemia occurs at rest, so blood flow meets needs. However, during exercise, arterioles further dilate to reduce resistance, but total resistance is still too high due to the dominance of stenosis. O2 demands cannot be met, so angina develops
576
How can stable angina be treated?
It can be relieved with GTN spray or other nitrates
577
How does stable angina affect an ECG?
Stable angina causes ST depression due to the ischaemia
578
What's variant angina and what causes it?
Variant angina is uncommon and caused by vasospasm, which can occur at rest and is often not linked to coronary artery occlusion. Excessive responses to vasoconstrictors leads to endothelium dysfunction (less NO produced)
579
What 3 drugs can be used for management of angina?
ß-blockers, CCBs and nitrates
580
What can minimise risk of angina?
Lifestyle changes, aspirin and statins
581
What is acute coronary syndrome?
A spectrum of potentially life-threatening conditions which are classed as medical emergencies
582
Can acute coronary syndrome be relieved by GTN spray?
No
583
What is done to investigate ACS?
An ECG and troponin T and I measurements
584
What causes a depressed ST segment and a STEMI in terms of ischaemia and depolarisation?
In healthy tissue, the ventricles are uniformly depolarised, so no current is detected on the ECG during the ST segment, and the line is isoelectric. In partial/less severe occlusions of coronary arteries, a small area of ischaemia which does not depolarise leads to injury current and depression of the ST segment on an ECG. In total/severe occlusion of a coronary artery, there's full wall thickness ischaemia which does not depolarise leading to injury current and elevation of the ST segment
585
What are the pharmacological therapies for ACS?
Morphine for pain, anti-platelets such as aspirin and clopidogrel, anti-thrombin such as heparins and NOACs, and log-term therapy from ß-blockers, CCBs and ACEi's
586
What treatment may be appropriate for an individual at moderate-high risk, with persistent symptoms and occlusions showing on angiography?
A coronary artery bypass graft (CABG) is given if 3 or more main coronary arteries are diseased, or the main left coronary artery is occluded and the occlusion position isn't appropriate for PCI. If 1 or 2 arteries are diseased, the patient can have percutaneous coronary intervention
587
Compare PCIs and CABGs
PCIs involve a less invasive procedure, but restenosis can occur. Restenosis can occur with CABG too, but it's less common with the mammary artery
588
Describe the process of a PCI
A balloon catheter is inflated in the area of the blockage to increase luminal diameter.
589
What vein is used to bypass the part of the functional end artery that's been occluded in a CABG?
The saphenous vein
590
How is a STEMI investigated?
ECG and troponins T and I measured
591
What are the pharmacological therapies for STEMI?
Morphine, aspirin, heparins, streptokinase, tissue plasminogen activators
592
What do thrombolytics do?
They cause fibrinolysis to breakdown the fibrin clot and increase the reperfusion zone
593
What's the preferred treatment of a STEMI?
Revascularisation within 2 hours of onset.
594
What are the life-threatening complications that can occur with revascularisation?
Cardiac failure from intraaortic balloon artificially increasing BP, rupture of the ventricular septum (leading to blood leakage between the ventricles), and arrhythmia
595
What's a pressor response?
An excitatory input from stimulation of arterial chemoreceptors or muscle metaboreceptors, which switches on reflexes to increase CO/BP/TPR
596
What is a depressor response?
An inhibitory input from stimulation of arterial baroreceptors, switching off reflexes, to decrease CO/TPR/BP
597
What do baroreceptors measure?
Blood pressure, but also blood flow indirectly
598
Where are baroreceptors found?
The walls of the carotid sinus and the aortic arch
599
At what point do action potentials fire most from baroreceptors?
Directly as the pressure changes, action potential fire the most, before they drop to an adapted frequency. With decrease in pressure, there's an initial period without action potentials, before a slower, adapted frequency of Ads firing picks up
600
What happens in the face of continued high or low pressure?
The threshold for baroreceptor activation changes
601
What happens to the baroreceptors in someone with hypertension?
They are less activated because the threshold becomes much greater, so blood pressure isn't as well regulated
602
What happens when baroreceptors are loaded?
A depressor reflex reduces blood pressure. The vagus nerve is stimulated, increasing parasympathetic response. Heart rate is slowed and vasodilation decreases TPR and therefore blood pressure
603
What happens when baroreceptors are unloaded ?
A pressor reflex maintains blood pressure/blood flow to vital organs. Increased sympathetic activity and decreased vagus activity leads to increased heart rate and force of contraction, so CO is increased. Arteriolar constriction means greater TPR. Venous constriction increases CVP, SV and CO via Starling's law
604
How does Ang II secretion lead to increase in blood volume?
Ang II stimulates aldosterone secretion, so there's Na+/H2O reabsorption in the kidneys, which leads to more water reabsorption into the blood
605
Where are veno-arterial mechanoreceptors found?
In the great veins entering the right atrium and in the walls of the right atrium
606
What happens when veno-atrial mechanoreceptors are stimulated?
Signals are sent to the brain about central venous rpessure and filling of the heart in diastole
607
What do ventricular mechanoreceptors tell the brain?
Whether the heart is over-distended or not
608
What fibres tell the brain about referred pain?
Sympathetic afferents (nociceptors)
609
Describe nociceptive sympathetic afferents and the basis of referred pain
These are chemo-sensitive ventricular afferent fibres that are stimulated by K+, H+ (lactate) and bradykinin (during ischaemia). The fibres converge onto the same neruones in the spinal cord as somatic afferents, which is the basis of referred pain
610
Describe veno-atrial mechanoreceptors
These receptors are stimulated by an increase in cardiac filling/ CVP. The initial pressor reflex increases sympathetic response and causes tachycardia.
611
What is the Bainbridge effect?
Reflex tachycardia due to rapid infusion of volume into the venous system (vena-atrial stretch receptors and pacemaker distension)
612
What happens in longer-term depressor reflex?
Increased diuresis and decreased blood volume. This happens in a feedback loop in response to changes in ADH, ANP and RAAS
613
What do ventricular mechaonreceptors do?
They sense over-distension of ventricles and this triggers a depressor reflex
614
Where are arterial chemoreceptors found?
In the carotid boy and aortic bodies (similar areas to baroreceptors)
615
What stimulates arterial chemoreceptors?
Low O2, high CO2, H+ and K+
616
What do arterial chemoreceptors regulate?
Ventilation and cardiac reflexes (during asphyxia, shock and haemorrhage)
617
What do muscle metaboreceptors respond to?
Increases in metabolites such as ATP, K+, lactate and adenosine
618
Where are muscle metaboreceptors found?
In skeletal muscle
619
What response do muscle metaboreceptors trigger?
A pressor response. Sympathetic activity is increased, causing tachycardia and increased arterial/venous constriction. This leads to increased cardiac output/BP
620
When are muscle metaboreceptors important?
In isometric exercise, where joint angle and muscle length do not change. They aid maintenance of blood perfusion to contracted muscle. These muscles undergo metabolic hyperaemia, allowing blood to flow to the contracted tissue
621
How are sensory receptor signals coordinated in the brain?
There are lots of different inputs into the NTS, which then sends inputs either to the nucleus ambiguous or into the caudal and rostral ventrolateral medulla. This is the basis for controlling cardiovascular reflexes
622
What is there between the caudal and rostral ventrolateral medulla?
There's an inhibitory pathway in the thermostat area which is really important for how the baroreceptors and arterial chemoreceptors work
623
Where does stimulatory input to baroreceptors send excitatory information?
To the caudal ventrolateral medulla
624
What happens when excitatory information is sent to the caudal ventrolateral medulla?
This excites an inhibitory pathway, which inhibits the rostral ventrolateral medulla and switches off sympathetic outflow to the heart and blood vessels to cause a depressor response
625
What happens when there's stimulatory input to arterial chemoreceptors or muscle work receptors?
Inhibitory input is sent to the caudal ventrolateral medulla. This switches on the rostral ventrolateral medulla and sympathetic nerves to generate a pressor response
626
What happens when baroreceptors are stimulated?
An excitatory neurone in the nucleus tracts solitarius is stimulated, which switches on the vagus nerve in the nucleus ambiguous and information is sent to the heart via vagal parasympathetic fibres to cause a depressor effect and reduction in heart rate
627
Describe the inhibitory link between respiration and the vagus nerve
Every time you breathe in, vagus activity switches off. During a long period of inspiration, heart rate goes up, and vice versa. This is to get more blood flow to transport the added oxygen through the body. This is called sinus tachycardia
628
What happens in syncope with regards to the vagus nerve?
The limbic system sends huge amounts of information to the vagus nerve, causing vagal bradycardia. This is a vaso-vagal attack. The bradycardia results in decreased cerebral blood flow and reduced oxygen delivery due to sudden decrease in arterial blood pressure
629
What effect would not having CVS reflexes have?
Without CVS reflexes, there'd be less control and blood pressure would be higher. CVS reflexes stabilise blood pressure
630
How does orthostasis affect the CVS?
On standing up, the CVS changes accordingly to the effect of gravity. At first, blood pressure falls (postural hypotension), however it quickly recovers due to homeostatic mechanisms. 3 smaller changes are increased heart rate, contractility and TPR
631
What's Bernoulli's law?
Blood flow= pressure energy + potential energy + kinetic energy
632
Why does gravity induce high blood pressures in the venous system?
Pressure is higher towards the bottom of the veins, so they become distended
633
How does orthostasis cause hypotension?
Decreased CVP leads to decreased EDP, leading to decreased SV and CO, and so decreased BP
634
What does poor perfusion of the brain lead to?
Dizziness and fainting
635
What factors worsen postural hypertension?
Drugs that reduce sympathetic activity or block vascular tone, varicose veins (impaired venous return), lack of skeletal muscle activity due to paralysis or forced activity, reduced circulating blood volume, increased core temperature (peripheral vasodilation, less blood volume available)
636
Why is postural hypertension a serious issue in the elderly?
It leads to them having falls
637
How does microgravity affect the CVS?
Standing and lying down is the same, so there's less need for ANS, RAAS, ADH and ANP systems to control blood pressure.
638
How is blood redistributed in the chest region in microgravity?
Initially, preload/EDP is increased, as is atrial/ ventricular volume. This is sensed by baroreceptors/ cardiac receptors. The sympathetic NS doesn't need to work because there's no gravitational pressures on blood flow. Decreased sympathetic NS actions, RAAS system and ADH release are the result of blood pressure being even throughout the body
639
Why is diuresis a symptom of microgravity?
More blood is going to the heart because there's greater stroke volume and cardiac output, so there's more blood supply to the kidneys and glomerular fltration rate must increase.
640
How does diuresis from microgravity affect the CVS?
The diuresis causes reduction in blood volume by 20%. In the long-term, blood volume is decreased; there's reduced stress on the heart, meaning the heart can suffer hypotrophy; and there'll be a general drop in BP, as less blood pressure is needed to drive circulation
641
What happens to the CVS on return from microgravity to gravity?
Severe postural hypotension will become apparent due to a hypotrophy of cardiac muscle, for which the baroreceptor reflex cannot compensate
642
What happens to the CVS when you exercise?
When you exercise, your heart must increase lung O2 uptake and increase O2 transport around the body, particularly to selective tissues e.g. exercising muscle. To prevent excessive afterload on the heart, BP must be controlled in the face of huge CO increase
643
How much does O2 uptake by pulmonary circulation increase during strenuous exercise?
13.5x
644
Via what 3 smaller changes does O2 uptake increase by 13.5x?
Heart rate can triple, stroke volume can increase by 1.5x, and arteriovenous O2 difference can triple to give a greater concentration gradient in the lungs
645
How is cardiac output increased during exercise?
Stroke volume increases to a maximum value, giving a plateau phase on Starling's curve
646
Describe exercise-induced tachycardia
Heart rate increases before exercise begins. On initiation of exercise, muscle mechanoreceptors provide fast feedback to the brain to increase heart rate. Vagal tone decreases and sympathetic activity increases
647
Describe exercise-induced stroke volume increase
Increased end-diastolic volume results in increased venous return/CVP through vasoconstriction. Increased contractility due to sympathetic activation of ß1-adrenoreceptors causes faster ejection of blood. End-systolic volume is decreased
648
What does vasodilation of arterioles in active muscle allows?
Vasodilation of arterioles in active muscle allows for more oxygen supply to myocardium and the skin during moderate exercise. There's metabolic vasodilation from increased K+/H+ and there's ß2-mediated vasodilation via circulating adrenaline
649
Why is blood pressure only mildly affected when CO increases by 4.5x?
Because skeletal muscle arterioles vasodilator and so TPR decreases to prevent excessive afterload on the heart
650
What are the 3 types of exercise?
Static. dynamic and resistive
651
What's resistive exercise?
Where static and dynamic exercise are combine and there's a high load, such as in weightlifting
652
Which form of exercise increases blood pressure more?
Static exercise increases BP more than dynamic exercise
653
Describe the sensory fibres in skeletal muscle
The sensory fibres have a small diameter. They're chemosensitive- stimulated by K+, H+ and lactate, which increase in concentration in exercising muscle tissue
