Cardiovascular System Flashcards
(328 cards)
1
Q
What level does the descending aorta pierce the diaphragm?
A
Aortic hiatus
T12
2
Q
What are the branches off the aortic arch?
A
The bracheocephalic trunk which branches off to form the right common carotid and right subclavian artery
left common carotid
left sublclavian
3
Q
What do the subclavian arteries supply?
A
The upper limbs
4
Q
What do the common carotid arteries supply?
A
The head and neck
5
Q
What returns blood from the upper left and right sides of the body?
A
Two brachiocephalic veins which join to form the superior vena cava
6
Q
What drains the head and neck and upper limbs?
A
Head and neck- internal jugular vein
Limbs- Left subclavian
Both join the brachiocephalic veins
7
Q
What are the names of the atrioventricular valves?
A
Left- mitral
Right -tricuspid
8
Q
What are the cusps of the pulmonary valve?
A
Left
Right
anterior
9
Q
What are the cusps of the aortic valve?
A
Left
Right
Posterior
10
Q
Where do coronary arteries arise from?
A
Aortic sinuses
Left and right cusps of the aortic valve
11
Q
How are antrioventricular valves joined to the heart?
A
Attached to papillary muscles by chordae tendinae.
Muscles are located on the inner surface of the ventricles
12
Q
How is the heart drained of blood?
A
The heart is drained by coronary veins
Great cardiac vein on left
Small cardiac vein on right
Drain into coronary sinus which drains into the right atrium
13
Q
What is cardiac muscle?
A
Specialised muscle tissue made up of cells that are not in synctium like skeletal muscle
Made up of cardiomyocytes which are connected via intercalated discs that allow the pasage of action potentials
14
Q
What is the sinoatrial node?
A
Group of cardiomyocytes that can initiate a heart beat
Located in right atrium, near entrance of superior vena cava
15
Q
What is the appearance of ventricular cells?
A
100x15 um
Rectangular appearance
16
Q
What is the purpose of t-tubule?
A
Carrying the wave of depolarisation from the surface to the cell
17
Q
How is cardiac muscle contraction initiated.
A
Action potentials travel through cardiomyocytes through the intercalated discs. Carried by t-tubules to L type calcium channel causing an influx of calcium into the cell. This calcium activated the sarcoplasmic reticulum calcium channel initiating an influx of calcium which binds to troponin. This allows tropomyosin to bind to the myosin head and form cross linkages. At the same time the action of Ca2+ Atpase actively transports calcium back into the sarcoplasmic reticulum and the Na+/ca2+ anti porter on t-tubule surface will restore calcium ions extracellularly
18
Q
What is the difference between active force and passive force?
A
Active force relies on cross bridge formation and linking
Passive force is more to do with elastic property
19
Q
Why does active force decrease after a certain muscle length?
A
Muscle has stretch too much
Number of cross bridges formed has decreased
20
Q
What is isometric contraction?
A
No shortening of muscle fibres but a force is generated
21
Q
What is preload?
A
The force that stretches the heart muscle before it contracts.
The passive force that is generated whilst the ventricles are filled with blood
22
Q
How can preload be measures?
A
End diastolic volume
End diastolic pressure
Right atrial pressure
23
Q
What is after load?
A
The force that needs to be overcome to cause contraction
Afterload is not seen in the resting state
24
Q
What is after load more dependant on?
A
Diastolic arterial blood pressure as the pressure of the left ventricles is higher than the right
25
What is the Frank-Starling relationship?
Increased diastolic fibre length results in increased ventricular contraction
26
What are the two properties of myofilaments that effect the Frank-Starling relationship?
Changes in the number of myofilament cross bridges
| Calcium sensitivity
27
Why are less actin-myosin cross bridges formed at lower lengths of actin molecules?
At lower lengths, the actin molecules double up on them selves, but at longer lengths they pull apart and expose the overlapped region
28
At greater sarcomere lengths, why is less calcium required to produce a given force?
At greater lengths, the affinity of troponin C for calcium increases
29
What is stroke work?
The work done by the heart to eject blood under pressure into the aorta and pulmonary artery
Stroke volume x pressure
30
What influences stroke volume?
Preload and afterload
31
Why must stroke volume remain the same for both ventricles?
If the amount of blood to the tissues is imbalanced it will result in odeoma.
32
What is the law of Laplace?
If the pressure in a cylinder is constant, the tension in its walls will increase with increased radius length
33
Why is there lower pressure in dilated cardiomyopathy?
Dilation leads to thinner walls and a larger radius leading to larger wall stress being generated
34
How is the slope of pre-potential affected by the sympathetic and parasympathetic nervous system?
Sympathic- steeper
| Parasympathetic- shallower
35
Why is there a reduction in outward potassium ion flow in the sinoatrial node cell?
They is net movement of Na+ but the cell has low permeability to K+
36
Why do ventricles have a long action potential?
Due to the inward movement of calcium ions due to voltage dependent calcium channels
37
Which drugs affect calcium?
Digoxin- increases calcium
| Verapamil- decreases calcium
38
What is the P wave?
Atrial depolarisation
| Atria Contract
39
What is the QRS complex?
Ventricles contract
40
What is the T wave?
Ventricular repolarisation
41
What is the mean frontal plane axis?
The general direction of an impulse of the heart
42
What is the name given to three connected limb leads?
Einthoven's triangle
43
What is the reference point when using standard limb leads?
The right foot
44
How are the limb leads connected?
Lead 1- right arm to left arm
Lead 2- right arm to left foot
Lead 3- left arm to left foot
45
Which are the theoretical leads?
AvR- connects the right arm to the mid point between the left arm and left foot
AvF- connects the left arm to the mid point between the right arm and left foot
AvL- connects the left foot to the mid point between the right arm and left foot
46
Which is the isoelectric lead?
The most flat lead?
47
What happens if an ECG shows no upward or downward deflection?
The wave of depolarisation is travelling directly between the electrodes of the lead
48
What is the normal range for the mean frontal plane axis?
-30 and +90 degrees
49
What is left axis deviation?
A mean frontal plane axis of less than -30 and is a result of aortic stenosis and when the left ventricle thickens
50
What is right axis deviation?
A mean frontal plane axis of above 90 degrees and is due to pulmonary pathophysiologies
51
What is the difference between the six standard limb leads and the chest leads?
Limb leads look at the coronal plane
| Chest leads look at the axial plane
52
What is the diameter of a capillary?
7um
53
What are the different types of capillaries?
Fenestrated
Discontinuous
Continuous
54
Give an example of a continuous capillary
The blood brain barrier is a modified form with no gap junctions
55
Where do discontinuous capillaries exist?
Bone marrow to let through red blood cells
56
How is flow calculated?
pressure gradient/vascular resistance
57
How is pressure gradient determined?
The gradient between the maximum pressure in the arterioles and the pressure in the capillaries
58
What is resistance?
The hindrance to blood flow as a result of the friction between the moving blood and the stationary wall vessels
59
What affects flow?
Blood viscosity
Vessel radius
Vessel length
60
What is the mean arterial pressure?
93mmHg
61
What is the pressure in the capillaries
37 mmHg
62
What is vascular tone?
A state of partial constriction
63
Why is the radius of blood vessels adjusted?
To supply blood flow depending on the metabolic needs of the tissue
To regulate arterial blood pressure
64
What undertakes the neural control of the blood pressure?
Cardiovascular centre in the medulla by the sympathetic nervous system
65
What mediates the sensitivities to change in flow in the brain and heart?
Brain- alpha receptors
| Heart- beta receptors
66
What is bulk flow?
A volume of protein free plasma that filters out of the capillaries and mixes with the surrounding interstitial fluid and is then reabsorbed
67
What are the starling forces?
Hydrostatic pressure which forces fluid out of the capillaries.
Oncotic pressure which causes fluid to be reabsorbed as the result of the osmotic pressure exerted by the proteins
68
Which end of the capillary does ultrafiltration occur?
Arteriolar end
69
Which end of the capillary does reabsorption occur?
Venous end
70
How does oncotic and hydrostatic pressure change throughout the capillary?
Hydrostatic pressure decreases further down the capillary.
| Oncotic pressure remains constant
71
Why are lymphatic capillaries blind ended?
They have no loop.
They are unidirectional.
Only purpose is to return net loss of fluid from the blood back to the heart
72
How does lymph return to the heart?
Drain into the right lymphatic duct and thoracic duct which drain into the left and right subclavian veins
73
How much lymph is returned per day?
3L
74
What is elephantiasis?
A parasitic infection which results in the blockage of the lymph vessels
75
What is the cardiac cycle?
The mechanical and electrical events which result in volume changes, pressure changes and sounds that are associated with a heart beat
76
What is end diastolic volume?
The amount of blood in the ventricles at the end of atrial systole
77
What is end systolic volume?
The amount of blood in the ventricles at the end of ventricular systole
78
What is stroke volume?
The amount of blood that has been ejected out of the heart in one heart beat
79
How can stroke volume be calculated?
Find the difference between end diastolic and end systolic volume
80
What is the ejection fraction?
Stroke volume/End diastolic volume
81
What are the stages of the cardiac cycle?
```
Atrial systole
Isovolumic contraction
Rapid ejection
Reduced ejection
Isovolumic relaxation
Rapid filling
Reduced filling
```
82
What happens when the atria contract?
The ventricles are topped off with any blood remaining in the atria
83
What is the cause of the first wave in the jugular venous pulse?
When the ventricles are being filled with blood, some blood pushes back against the jugular vein
84
What heart sound may be heard during atrial systole due to problems?
S4
85
What is the cause of the heart sound S4?
Pulmonary embolism, congestive heart failure, tricuspid incompetence
86
What causes the atrioventricular valves to close?
The ventricular pressure exceeds atrial pressure
87
Which sound correlates to the closure of the atrioventricular valves?
S1
88
What causes the opening of the semilunar valves?
The ventricular pressure exceeding the aortic pressure
89
What causes reduced ejection?
The semilunar valves begin to close as the pressure gradient between the aortic and ventricular pressure begin to decrease.
90
Which stage in the cardiac cycle marks the end of systole?
Isovolumic relaxation
91
What is the dichrotic notch due to?
Rebound pressure on the aortic valve as a result of the relaxation of the distended aortic wall
92
What causes the second jugular pulse?
Blood pushing against the tricuspid valve as the atria fill with blood
93
If S3 is heard, what stage of the cardiac cycle will it be present?
Rapid ventricular filling
94
What does S4 correspond to?
Mitral incompetence
Turbulent filling
Severe hypertension
95
What else can reduced ventricular filling be called?
Diastasis
96
What are the standard systolic/diastolic pressures for the left and right side of the heart?
120/80 mmHg
| 25/5 mmHg
97
When may PAWP be increased?
Left ventricular failure
| Mitral stenosis
98
What do the points of the pressure volume loop correspond to?
1- end diastolic volume
2- Aortic pressure has been encountered
3- end systolic pressure
4- opening of atrioventricular valves
99
What do the stages between the points correspond to?
1 & 2 - isovolumic contraction
2&3 - ejection
3&4 - isovolumic relaxation
4&1 - filling of the ventricles
100
What represents preload on the flow volume loop?
Point 1
101
What represents after load on the flow volume loop?
Between points 2 and 3
102
What does the horizontal distance between isovolumic contraction and relaxation represent?
Stroke volume
103
How can the contractility of the heart be measured?
Using the ejection fraction
104
What is the duration and amplitude of the P wave
0. 11 seconds
| 2. 5 mm in lead II
105
How long is the PR interval
0.12-0.2 seconds
106
How long is the QRS complex?
0.12 seconds
R wave in V6 - 25 mm
R wave and S wave in V1 - 35 mm
107
How long is the QT interval?
0.38-0.42 seconds
108
In which leads can the T wave be inverted without being abnormal?
lead III, avr, v1, v2
109
How would you calculate heart rate from an ECG?
Divide 300 by the number of large squares between the QRS segments
110
What is bradycardia?
A heart rate less than 60 beats per minute
111
What is tachycardia?
A heart rate more than 100 beats per minute
112
What is a sinus rhythm?
Each P wave is followed by a QRS complex
113
What may cause an occasional extra QRS complex?
Ectopic beat
114
What does the QRS complex tell you about the heart?
Its orientation within the chest wall
The thickness of the ventricular muscle
Abnormalities in the direction of ventricular depolarisation
115
How does the ECG show first degree heart block?
If the PR interval is prolonged but still followed by the QRS complex
This is due to delayed conduction through the AV node
116
How does the ECG show second degree heart block type 1?
If successive PR waves get successively longer until one is not followed by a QRS complex and then the pattern returns to normal
Wenkebach's phenomenon
117
How does the ECG show second degree heart block type 2?
If the PR intervals are constant but occasionally not followed by the QRS complex
118
How does the ECG show complete heart block?
There is no relationship between the PR intervals and QRS complex as the atria and ventricles depolarise separately
119
Why may a PR interval appear to be shorter than usual?
An accessory pathway is present which causes electrical activity to be conducted from atria to ventricles more rapidly than usual
120
What may an increased amplitude of the QRS complex suggest?
Left ventricular hypertrophy
121
What may a reduced amplitude of the QRS complex suggest?
Obesity
Chronic airways disease
Pericardial effusion
Hyperinflated lung
122
What may cause ST depression?
Drugs
Myocardial ischaemia
Ventricular hypertrophy
123
What may an elevated ST segment suggest?
Acute myocardial infarction
124
What may cause a prolonged QT interval?
Drugs
Hypocalcaemia
Ramano- Ward syndrome
125
What can T wave inversion suggest?
Previous infarction
Myocarditis
Hypertrophy
126
What is the ECG appearance of sinus tachycardia?
Absent P waves replaced by f waves
| 350-600 beats per minutes
127
How may atrial fibrillation lead to thrombus?
It is irregular beating of the atria
Irregular flow of blood
Stasis of blood
Thrombus
128
What causes atrial flutter?
Premature electrical impulse arising from the atria
129
What are general symptoms of heart block?
Syncope
Lightheadedness
Palpitations
130
What are blocks that occur below the AV node?
Infra-hisian blocks
131
What are blocks that occur in the fascicles of the left bundle branch?
hemiblocks
132
How is flow achieved?
By the action of the muscular pump of the heart which generates a pressure gradient that propels blood through a series of tubes
133
How far is a cell from a capillary?
10um
134
What acts as a reservoir for blood volume?
Veins and venules
135
What act as dampening vessels?
Large arteries
136
What is ohms law?
Voltage = flow x resistance
137
How does blood flow?
Laminar flow
138
What is laminar flow?
Fluid flows in layers or is streamlines
139
What is shear rate?
The viscosity gradient at any point?
140
What is shear stress?
Sheer rate x viscosity
141
How does velocity of layers of blood increase as you move away from the wall?
Increases
142
What does high shear stress promote?
Cell survival
Cell alignment with direction of flow
Secretion of substances that promote vasodilation and anticoagulation
143
What is transmural pressure?
Pressure in the wall of the vessel
144
What is the Windkessel effect?
Dampening the magnitude of pressure change
145
Why is most blood volume stored in the veins?
Veins are more compliant at low pressures than arteries
146
What problems does standing up pose?
The effect of gravity increases pressure in lower limbs.
Veins are compliant so the volume of blood in veins increases.
Volume of blood returning to the heart decreases so cardiac output and blood pressure could fall.
147
How are the problems that could be caused as a result of standing up solved?
Sympathetic nervous system is activated
Venous smooth muscle constriction- to stiffen the veins
Constriction of the arteries- increase resistance and maintain blood pressure
Increase contractility of the heart and heart rate
Myogenic vasoconstriction
Use of muscle and respiratory pumps
148
What are varicose veins?
Dilated superficial veins
149
Which layer is present in ever blood vessel in the body?
Vascular endothelium
150
What are the functions of the vascular endothelium
```
Vascular tone management
Thrombostasis
Absorption and secretion
Growth
Barrier
```
151
Which mediators have an effect on vascular tone?
```
Nitric oxide- vasodilation
Prostacyclin - vasodilation
Thromboxane- vasoconstriction
Endothelin 1- vasoconstriction and vasodilation
Angiotensin II- vasoconstriction
```
152
Which mediators have an effect of platelet aggregation
Nitric oxide- inhibits
Prostacyclin- inhibts
Thromoxane- activates
153
Which two mediators can arachidonic acid form?
Thromboxane A2
| Prostacyclin
154
How is prostacyclin formed?
COX enzyme converts arachidonic acid into PGH2, which is a precursor and then it is converted into prostacyclin using prostacyclin synthase
155
What is the alternative route for arachidonic acid?
Form leukotrienes
156
What is the prostacyclin pathway?
Leave the cell on the luminal cell
On the basolateral membrane bind to prostacyclin receptors on smooth muscle cells which activate adenylyl cyclase and protein kinase A
157
How is endothelin 1 produced?
From the nucleus of endothelium cells
158
Which endothelin 1 receptors of found on smooth muscle cells?
ETA and ETB
159
which endothelin receptors are found on endothelium cells?
ETB
160
How does endothelin produce a vasodilatory response?
It up regulates eNOS which stimulates NO release
161
Give an example of an angiotensin receptors inhibitor
Candestartan
162
Give an example of an ACE inhibitor
Ramripil
163
Give an example of a calcium channel blocker
Amlodipine
164
What is the precursor of nitric oxide?
L-arginine
165
What is the secondary messenger of nitric oxide?
Guanylyl cyclase
166
What is the receptor for prostacyclin?
IP1
167
Which postganglionic neurones secrete acetyl choline?
Sweat gland,
| Ach acts on sweat receptors
168
What does sympathetic innervation to the adrenal medulla result in?
Secretion of adrenaline and some noradrenaline
169
Why doe sympathetic innervation to the heart increase cardiac output?
Exerts a ionotropic effect on the cardiac muscle- increasing the force of contractility of the heart- increasing stroke volume
Exerts a positive chronotopic effect, increase heart rate
170
Which blood vessels vasodilator when sympathetically innervated?
Ones which have
Cholinergic fibres
B adrenergic fibres
171
How is noradenaline synthesised?
Amino acid tyrosine is converted into DOPA using tyrosine hydroxylase
DOPA is converted into Dopamine using DOPA decarboxylase
Dopamine is stored in secretory vesicle with Dopamine Beta hydroxylase which converts it into noradrenaline
172
How is over transmission of noradrenaline prevented?
On post synaptic neurones- Converted into an inactive form using catecholamine-O- methyltransferase (COMT)
on pre synaptic neurone - taken up by secretory granules to be used as neurotransmitter using ATP
broken down into metabolites using mitochondria using monoamine oxidase A MAO- A
173
Where are alpha 1 adreno receptors found?
Post synaptic neurones
174
Where are alpha 2 adreno receptors found?
Pre synaptic neurones
175
Where are B1 adrenoreceptors found?
cardiac muscle and smooth muscle of GI tract
176
Where are B2 adrenoreceptors found?
Uterine, bronchial and vascular smooth muscle
177
Where are B2 adreno receptors found?
Fat cells
178
Which receptors does adrenaline react with?
All receptors
179
Which receptors does noradrenaline react with?
Alpha
| Beta 1
180
Which receptors does dopamine react with?
Alpha 1
| Beta 1
181
Which receptors does isoprenaline react with?
Beta receptors
182
Where is renin secreted from?
Kidney
183
What stimulates renin release?
Low blood pressure
Low sodium level
Sympathetic innervation of B1 adrenoreceptors
184
Where is ACE secreted from?
Epithelial cells of the lung
185
What are the functions of angiotensin II?
Potent vasoconstrictor
Enhances action of peripheral noradenaline
Increase sympathetic discharge
Catecholamine release from adrenal response
186
What type of receptor is the AT 1 coupled receptor?
G1 and Gq protein coupled receptor
187
Where are AT 1 receptors located?
Kidneys
Bood Vessels
Brain
Heart
188
What is auto regulation?
The intrinsic capacity to compensate for any perfusion changes sensed
189
What are the two theories of auto regulation?
Metabolic
| Myogenic
190
What is the metabolic theory?
As blood flow changes, the concentration of metabolites changes therefore the radius of vessels changes to accommodate the metabolites. This can be in response to c02, adenosine, protons and potassium ions.
For example, if the blood flow is lower, metabolites will accumulate so the radius increases
191
What is the myogenic theory?
As blood flow increase, pressure rises and causes a stretch of the smooth muscles. Muscles respond to the stretch by undergoing vasoconstriction.
192
Which mediator from platelets causes constriction?
Serotonin
193
Where does vasopressin come from?
Neurohypophysis
194
What do the sympathetic and parasympathetic nervous system control?
Sympathetic- circulation
| Parasympathetic- heart rate
195
What does the sympathetic nervous system not innervate?
Capillaries
Precapillary spincters
Metarterioles
196
How does noradrenaline cause vasoconstriction?
Binds to alpha 1 receptors
197
What receptors does adrenaline preferentially bind to?
Beta 2
198
How can adrenaline bring about vasodilation?
Massive stimulation of the sympathetic nervous system can lead to increase concentration of adrenaline and some will bind to a receptors causing vasodilation
199
What does the vasomotor centre consist of?
Pressor area
Depressor area
Cardioregulatory inhibitory centre
200
How does the vasomotor centre transmit impulses?
Distally through the spinal chord
201
How do vessels receive sympathetic innervation?
Via post ganglionic neurones
202
How does the vasomotor centre stimulate vasoconstriction and vasodilation
Pressor area stimulates sympathetic nervous system
| Depressor inhibits sympathetic nervous system
203
How does adrenaline lead to increased contractility?
Adrenaline binds to beta 1 receptors on the heart which activates the cAMP pathway which causes a cascade effect. Upregulates calcium ATPase and the sarcoplasmic reticulum calcium channel
204
Which extrinsic factors increase the contractility of the heart?
Increased sympathetic action
| Adrenaline
205
Which intrinsic factor increase the action of the heart?
Increased venous return which increases end diastolic volume
| Increased respiratory movements lead to a decreased inter-thoracic pressure leading to lower end diastolic volume
206
How do baroreceptors feed back to the brain from the carotid sinus and aortic arch
Carotid sinus- glossopharyngeal nerve
| Aortic arch - vagus nerve
207
What is the most sensitive range of the baroreceptor reflex?
90-100mmHg
208
By which mechanism is the baroreceptor reflex controlled?
Recipricol innervation
209
How does reciprocal innervation work?
Afferent input via the parasympathetic nervous system is coupled with an inhibitory sympathetic neurone.
Therefore blood pressure is decreased two ways.
Parasympathetic stimulation and inhibited sympathetic innervation decrease heart rest
Inhibited sympathetic innervation decreases stroke volume
210
Why does gravity increase pressure in the foot?
Due to the hydrostatic pressure of the blood vessels
211
Why may standing cause stroke volume to decrease?
Increased gravity causes hydrostatic pressure of the blood vessels to increase. This causes more blood to pool in the veins as veins are more compliant.
The increase in hydrostatic pressure can also cause blood to be driven out of the arteries which could result in oedema.
As a result of venous distension that is a reduction of circulating blood volume which decreases blood pressure and end diastolic volume and ultimately stroke volume.
The hypotension is transient
212
What are the compensatory mechanisms for standing?
Baroreceptors sense a drop in pressure and relay this back to the vasomotor centre which release sympathetic discharge to the heart.
Disinhibition occurs where activation of the parasympathetic nervous system is halted alongside the inhibition of the sympathetic nervous system.
The sympathetic nervous system exhibits a chronotopic and ionotropic affect on the heart.
Vasoconstriction also allows less blood to be pooled in compliant veins and increases resistance. More blood enters the circulation, increasing end diastolic volume and stroke volume
213
How does the sympathetic nervous system allow the kidneys to release renin?
Causes vasoconstriction of the sphlancic and renal beds
214
What does the problems posed by haemorrhage differ from change in posture?
Haemorrhage results in an actual reduction in the volume of circulating blood
215
What are the compensatory mechanisms for haemorrhage?
Hydrostatic pressure everywhere falls
Colloid osmotic pressure increases slightly due to fluid loss so solute concentration increases.
Autotransfusion occurs.
Low renal blood flow activates the renin-angiotensin system
Angiotensin II allows more renin to be released
Aldosterone increases sodium retention and water retention
Vasopressin increases water retention
Urinary output is decreased
More fluid is able to be kept in the body
216
What is auto transfusion?
The net reabsorption of fluid from the interstitial fluid into the blood.
Erythrocytes are not replaces.
217
How much blood loss can the compensatory mechanisms for haemorrhage cope with?
10%
218
What is the challenge that exercise presents?
Maintaining blood pressure whist keeping blood flow at a high rate
219
During exercise, which areas receive increased sympathetic output?
Gi tract
| Kidneys
220
During exercise which area received decreased sympathetic output?
Skin
221
What negative things occur during exercise?
Increased capillary pressure across muscle leads to fluid loss
Salt and water is lost in sweat
222
During exercise, why is there a net increase in cardiac output?
Increase sympathetic innervation and decreased parasympathetic innervation to the heart leads to increased stroke volume
Skeletal muscle pumps lead to increased venous return
223
What is primary haemostasis?
Due to the release of chemical mediators from the endothelium, the vessel constricts which confines injury to one place.
Platelet aggregation causes the formation of an unstable plug
224
What is secondary haemostasis?
The unstable plug formed into primary haemostasis is stabilised with fibrin.
The clot is dissolved in a process called fibrinolysis
225
What are glycoproteins gp1a and gp1b?
Integrins that are present on the surface of platelets
226
Describe platelet adhesion
After a vessel has been damaged, collagen is exposed.
This causes the binding of circulating von Willebrand factor.
Platelet will bind to this via GpIb
Platelets will bind directly to this via GpIa
Platelets that activate will undergo a morphological change and project filopodia
227
What initiates platelet aggregation?
ADP and prostaglandins from the activated platelets which will cause circulating platelets to bind and become activated.
228
Why is calcium required for the binding of further platelets?
Fibrinogen causes the binding of adjacent platelets via gpIIa and gpIIb
Fibrinogen needs calcium
229
What is released during platelet activation?
Thromoxane
Prothrombin
Coagulation factor IIa
230
Why are clotting factors formed?
Liver- many clotting factors
Endothelial cells- von Willebrand factor
Megakaryocytes- precursors of platelets
231
How is inappropriate coagulation prevented?
Coagulation factors are kept separate from the initiators of coagulation
232
How can coagulation be initiated?
Vessel damage- intrinsic pathway
| Trauma- extrinsic pathway
233
Explain the intrinsic pathway
The exposed collagen allows the first coagulation factor to bind
Factor XII is converted to Factor XIIa
Factor XIIa converts XI to XIa
Factor XIa converts IX to IXa
In the presence of factor VIIIa and PI, factor IXa converts X to Xa which activates the common pathway
234
Describe the extrinsic pathway
Trauma causes the conversion of Factor VII to VIIa under the influence of a tissue factor
Tissue factor and VIIa combine to form the complex TF-VIIa
TF-VIIa causes Factor X to be converted to Xa, activating the common pathway
TF-VIIa also contributes to the intrinsic pathway by converting IX to IXa
235
Describe the common pathway
Father Xa converts Factor II (prothrombin) to IIa in the presence of Va and PI
IIa (thrombin) converts fibrinogen into insoluble fibrin
IIa also converts XIII into XIIIa
IIa activates more platelets
236
What is the role of Factor XIIIa
Allows cross linkages between the fibrin molecules leading to the formation of the fibrin plug
237
What causes plasminogen and plasminogen activating factor to bind?
The presence of the fibrin clot to form active plasmin
238
What is the purpose of plasmin?
To degrade the fibrin clot, leaving being fibrin degradation products
239
How is coagulation inhibited?
Direct - antithrombin
| Indirect- protein C
240
What does antithrombin inhibit?
Factors IXa, Xa, XIa
| Thrombin
241
Why is heparin given for immediate anticoagulation in venous thrombosis and pulmonary embolism?
It accelerates the action of antithrombin
242
Explain indirect inhibition of coagulation
The endothelium expresses thrombomodulin which thrombin binds to.
Protein C binds to this and causes activated protein C.
Activated protein C break down Factors Va and VIIIa
243
Which genetic variation process causes coagulation to be more prominent?
Factor Va Leiden cannot be broken down by protein C and protein S
244
What are the risk factors of thrombosis?
Antithrombin deficiency
Protein S deficiency
Protein C deficiency
Factor Va Leiden
245
What can defects in primary haemostats exist?
Absent collagent
Lack of von Willebrand factor
Lack of platelets
246
What increases the lack of collagen?
Steroid use
| Age
247
What causes lack of platelets?
Aspirin
| Thrombocytopenia
248
What are the characteristics of defects in primary haemostasis
```
Bleeding is immediate
Easy bruising
Prolonged epistaxis
Menorrhagia
Petechiae
Bleeding after trauma or surgery
Prolonged gum bleeding
```
249
What is an example of a defect in secondary haemostasis?
Haemophilia
250
What is diluted coagulapathy?
Dilution of blood by transfusion leads to there not being enough coagulation factors
251
What is dissemated intravascular coagulapathy?
Excessive protein consumption
Small clots form throughout the body using up the clotting factors and normal coagulapathy being disrupted
Being activated monocytes and macrophages can express tissue factor on their surface
252
How may dissemated intravascular coagulapathy lead to organ failure?
Formation of many micro clots means fibrynolisis is activated a lot using up fribinogen. Fibrinogen can deposit fibrin and block up organs
253
What are the characteristics of secondary haemostatic defects?
Delayed bleeding
Deeper bleeding in joints and muscles
Nosebleeds are rare
Bleeding occurs after trauma or surgery after intramuscular injections
254
What can cause clot instability?
Excess plasmin
Excess plasminogen activating factor
Deficient antiplasmin
255
What can arterial thrombi cause?
Myocardial infarction
Limb ischaemia
Strokes
256
What can venous thrombi cause?
Oedema
| Pain
257
What are risk factors for venous thrombosis?
Age
Previous illness and events
Genetics
258
What is Virchow's triad?
Blood stasis
Hypercoagulability
Endothelial injury
259
What type of thrombi can blood stasis cause?
Venous
260
What type of thrombi can hyper coagulability cause?
Arterial and venous
261
What type of thrombi can endothelial injury cause?
Arterial
262
What are foam cells?
Macrophages that migrate to the endothelium and uptake lipids that have been deposited
263
Where do LDLS deposit in the endothelium?
Under the tunica intima and bind to matrix proteoglycans
264
What oxidises the LDL's?
Free radicals
265
What do oxidised LDLs release?
Aldehydes
266
How is cholestrol released from LDL's?
Products of LDL oxidation bind to apoproteins on the surface of LDL's
267
Why do scavenger receptors on macrophages keep on uptaking modified LDL's?
They have no negative feedback system
268
Why may inflammation occur as a result of foam cells?
They secret inflammatory mediators
269
How do foam cells forms a plaque?
They undergo atoptsis
| More monocytes are recruited which also secrete inflammatory mediators
270
How do vascular endothelial cells aid the development of lesions?
Act as a barrier site to leukocytes and allow them through
| Function as leukocyte recruitment in response to inflammatory mediators causing more inflammation
271
How do platelets aid the development of lesions?
Important in thrombus formation
Release cytokines to recruit other platelets
Release growth factors
272
How do monocytes/macrophages aid the development of lesions?
Become foam cells
Secrete cytokines and growth factors
Source of free radicals leading to oxidation of LDL's and more foam cells being formed
Secrete mettaloproteinases which break down extracellular matrix and allow more clots to form and LDL's to bind
273
How do vascular smooth muscle cells aid the development of lesions?
Allow migration of cells and LDL's
Required for collagen synthesis
Required for formation of fibrous cap
274
How do T-lymphocytes aid the development of lesions?
Important in activating macrophages
275
Why are areas where arteries bifurcate prone to plaque formation?
Disruption of laminar flow
Mini-reversals of flow of blood
More turbulent
More vulnerable to damage
276
What is plaque erosion?
Breakdown of the endothelial lining of the plaque without full rupture of the fibrous plaque
277
What is plaque rupture
Rupture of the fibrous cap which separates the plaque from the blood
278
What factors predispose to an instable plaque?
```
Lipid rich core
Thin fibrous cap
Low collagen
Low vascular smooth muscle cells
Infiltrative macrophages
Neurovascularisation
```
279
What degrades collagen?
Macrophages
280
What will transient ischaemic attack in the eye cause?
Amaurosis fugax
281
What initiates the formation of the vasa vasorum?
Vascular endothelial growth factor
282
Where are vasa vasorum located?
Tunica adventitium
283
What is the function of the vasa vasorum?
Supplied larger blood vessels with smaller vessels
| Recruits monocytes
284
Why can the vasa vasorum cause haemorrhage?
Extra blood supply is weak and prone to rupture
285
What is stenosis?
The gradual narrowing of arteries
286
What are the main types of cell involved in development of atherosclerosis?
Vascular endothelial cells
White blood cells
Platelets
Vascular smooth muscle cells
287
What do the three layers of the vascular endothelium consist of?
Tunica intima- endothelium
Tinica media- smooth muscle cells
Tunica adventitia - vasa vasorum, nerves
288
What are the functions of the endothelium?
Vascular tone and permeability
Haemstasis and thrombosis
Inflammation
Angiogenesis
289
What is angiogenesis?
When new blood vessels sprout from currently existing ones
290
What is the Janus paradox?
The fact that in atherosclerosis, angiogenesis has both beneficial and harmful benefits.
Will vascularise the plaque therefore promote its growth
Will also reach areas occluded by the plaque and therfore prevent damage post ischaemia
291
What is senescence?
The limited proliferative capacity of human cells in culture
292
What is the cause of senescence?
The shortening and dysfunction of telomeres
293
What can induce senescence?
Cardiovascular risk factors eg.
Smoking
Oxidative stress
294
Which chemical in red wine has beneficial effects in preventing atherosclerosis?
Resveratrol
295
What is hermatic action?
Beneficial at low doses
| Cytotoxic at high doses
296
Where are endothelial progenitor cells derived from?
Circulating bone marrow CD34+ stem cells
297
What causes the mobilisation of EPC's?
Ischaemia
Pro-angiogenic factors
Statins
298
Why may EPC's be injected at the site of ischaemia?
Migrate to site and contribute to re-endothilisation and angiogenesis
299
What is hypertension?
A persons blood pressure is constantly over 140/90 mmHg
| The level of blood pressure above which investigation and treatment could do more good than harm
300
What influences primary hypertension?
Genetics
| Environment
301
Give example of monogenic causes of hypertension
Liddle's syndrome
| Mineralcorticoid excess
302
What are the environmental factors of hypertension?
```
Dietary salt
Alcohol Consuption
Obesity
Pre natal environment
Pregnancy
```
303
What are the causes of secondary hypertension?
```
Renal disease (renal artery stenosis
Tumours secreting catecholamines
Tumours secreting aldosterone
Conn's sydrome
Oral contraceptive pill
```
304
What is phaoechromacytoma?
Tumours secreting catecholamines
305
What is Conn's sydrome?
Tumours secreting aldosterone leading to hyperaldosteronism.
More fluid retention and greater blood volume
306
What are the risks associated with hypertension?
```
Coronary heart disease
Atrial fibrillation
Stroke
Retinopathy
Heart failure
```
307
How can hypertension call chambers to become smaller?
Causes left ventricular hypertrophy causing cardiac remodelling to compensate for the higher blood pressure
308
What can coronary artery disease present with?
Arrhythmia
Acute coronary syndrome
Coronary artery death
Heart failure
309
What is angina pectoris marked by?
Discomfort in shoulders, chest, arms, jaw and back
310
How is angina relieved?
Rest
| Nitroglycerin within 5 minutes
311
What are the treatments for angina?
Improving blood supply by revascularisation
Reducing demand for metabolic oxygen by reducing heart rate
Preventing development of atherosclerosis
312
What is myocardial infarction?
Cell death arising from interrupted blood flow to the heart
313
Which cardiac protein can be used to detect necrosis of cardiac tissue?
Troponin
314
Which of Virchow's triad has the most dominant influence in arterial thrombosis?
Endothelial injury
315
Which thrombi are common in arterial thrombosis?
White thrombi - platelet rich
316
Which thrombie are common in venous thrombosis?
Red thrombi- fibrin rich
317
What is the nature of white infarcts?
Anaemic
318
What is the nature of red infarcts
Haemorrhagic
319
What type of organs to red and white infarctions affects?
White- kidney and spleen (solid)
| Red- lung (loose)
320
What are the characteristics of red infarctions?
Occlusion of a vein
Loose tissues that allow blood to collect in the infarcted zone
Tissues with dual circulatory system
Reperfusion of previous ischaemic tissue
321
What occurs after an infarction
There is cardiac remodelling
Infarction replaced with fibrous tissue
Infarct is expanded, thinned and elongated
Left ventricle dilates to reduce wall tension and maintain cardiac output
Non infarcted tissue undergoes electrical recoupling
322
What are the adverse affects of remodelling?
Increased mixed venous oxygen
Ventricular arrhythmia's and fibrillation
Mitral regurgitation
Decreased myocyte shortening
Increase systolic and diastolic wall tension
323
What is given to reduce affects of remodelling?
ACE inhibtors
| Beta blockers
324
What is reperfusion injury?
Increased damage to heart tissue. Restored blood flow reintroduces oxygens in cells which damages cellular proteins, DNA and plasma membrane
325
How is reperfusion injury reduced?
Cardioprotection
326
What is the acute management of thrombotic burden?
Thomboectomy and giving drugs
327
What is the recurrent management of thrombotic burden?
Anti-coagulants and anti-platelets
328
How are plaques stabilised?
Put in a stent
| Give statins and ACE inhibitors
