This document discusses John Palmer's chest pain and Starling's Law. It provides questions and answers on topics related to cardiac output, preload and afterload, Starling's Law, differences between cardiac and skeletal muscle, factors that affect conduction of the cardiac action potential, the electrocardiogram, and types of red blood cells.

1. John Palmer’s Chest Pain
Starling’s Law
1. What variables can change cardiac output?1
2. What are after-load and preload?2
3. What is Starling’s Law?3
4. What is the main difference between cardiac muscle and skeletal muscle?4
5. Why is cardiac muscle more sensitive to stretch than skeletal muscle?5
6. Why is Starling’s Law important?6
7. Where would you calculate blood pressure in the lungs?7
8. What happens to stroke work and end diastolic pressure (i) In exercise (ii) in
heart failure?8
9. Why is cardiac output low in a dilated heart?9
1 Filling pressure of right heart, function of the heart-lung unit (e.g. pulmonary edema?), Resistance to
outflow from left ventricle, Influence of ANS on B1 receptors
2 After-load is the tension on the wall of the left ventricle during ejection. Preload is the resistance to outflow
from the left ventricle, these are related to the volume of blood that goes into the ventricle during diastole.
3 The rule that energy released during contraction depends on the initial fibre length, so stretching the
muscle and therefore increasing the sarcomere length (Z band to Z band) (e.g. by increasing venous influx)
also increases force.
4 Cardiac muscle contains tropomyosin, which covers the myosin cross bridge binding sites until removed by
Ca2+ and TnC to expose binding site. Cardiac muscle is made up of intercalated disks, doesnʼt tire like
skeletal muscle and relies on Ca2+ in the cells to maintain a prolonged AP ʻplateauʼ which is not the case in
skeletal muscle (which only depends on Na+ and K+ for action potentials).
5 As the muscle stretches, troponin C (part of the troponin complex present in cardiac muscle) becomes
more sensitive to calcium.
6 Left and right sides need to be equal/balanced or fluid will be forced in or out of lungs. (Pulmonary Edema)
7 Pulmonary venous pressure is considered to be equal to lung pressure
8 In exercise = stroke work and EDP increase because the heart is distended, in heart failure both decrease
because the heart is grossly distended and has gone beyond optimum stretch potential
9 Although more stretch equals more force this is only true to a point. In a grossly distended heart Laplaceʼs
Law (pressure = 2x tension/radius), so a greater radius actually means less pressure.

2. 10.What does an increase in blood volume do to CVP and CO?10
11.What effects does digoxin have on the heart and venous system?11
12.How do you work out CO from HR and SV?12
13.How do you work out SV from EDV and ESV?13
Initiation of the Heart Beat
1. What is the equilibrium potential for potassium?14
2. What are the approximate lengths (in milliseconds) for a nerve AP and a cardiac
AP?15
3. What causes cardiac muscle to contract?16
4. ... and to relax?17
5. Which class of anti-arrhythmic drugs (i) block Ca2+ channels, (ii) block K+
channels (iii) block Na+ channels?18
6. Why is there a bigger spike in voltage in an action potential through the Purkinje
fibres than in the ventricles?19
10 Both increased
11 Increases contractility and decreases CVP as more blood pumped into arteries.
12 Heart rate (bpm) x stroke volume
13 ESV minus EDV gives you the difference (i.e. the volume pumped out of the heart in one stroke/beat)
14 -90mv, K+ maintains the resting potential for cardiac muscle
15 Nerve (3ms), Cardiac (300ms)
16 Na+ channels open, influx of Na+, fast upstroke from -90mv, channels start to close when charge gets
nearer to 0mv and when over 0mv, voltage gated L-type Ca2+ channels open which causes a large influx of
Ca2+
17 Ca2+ gradually decays during ʻplateauʼ region of AP and when dips below 0mv then K+ channels open up,
efflux of K+ speeds up repolarisation to -90mv (which is the equilibrium potential of K+)
18 Class IV block Ca2+ channels, Class III block K+ and class I block Na+
19 Purkinje fibres are specialised conduction vessels and have a greater surface area so can absorb Ca2+
more quickly.

3. 7. How is conduction of a cardiac action potential slowed by the AV node?20
8. What is the Ca2+ threshold (i.e. voltage at which Ca2+ channels are opened) in
the SAN?21
9. What do delayed rectifier K+ channels have to do with heart rate?22
10.Why is there little inherent decay of K+ in skeletal muscle, whereas there is in
cardiac muscle?23
11.What do ‘If’ channels do?24
12.How does parasympathetic stimulation slow the heart rate?25
13.How are cardiac muscle cells connected to ensure electrical transmission
between them?26
14.What factors (outside the cell) might slow the rate of conduction of the wave of
depolarisation?27
15.What is the speed of AP conduction in the atria,AVN and bundle of His?28
20 AV node cells do not contain fast upstroke Na+ channels so only depolarize when resting potential
naturally decay is large enough to be picked up by the Ca2+ channels, upstroke is entirely driven by calcium
and is therefore slower than in the rest of the heart.
21 -45mv (resting potential -90mv)
22 Delayed rectifier K+ channels in the SAN control the rate of decay of the cardiac action potential. The
channels gradually decay, so K+ enters at a slower rate, meaning RMP can be maintained for a shorter
period of time and HR increases.
23 The 1B (basal current, i.e. the current outside the cell) in skeletal muscle cells is much lower than in
cardiac cells. This is the reason K+ equilibrium potential is reached in cardiac muscle but not skeletal
muscle.
24 ʻIfʼ channels control how much Na+ enters the cell, and therefore how much K+ comes out (via basolateral
Na+/K+ATPase), so blocking ʻIfʼ blocks decay of action potential because less K+ leaves cell. Sympathetic
stimulation causes increased firing of action potentials by increasing activity of If channels, increasing rate of
AP decay and so frequency of APs.
25 Blocking K+ channels in the SAN, causing hyperpolarisation and so takes longer for natural decay of AP
and longer to repolarise.
26 Intercalated disks are connected by a desmosome, between these are gap junctions containing
ʻconnexonsʼ which are channels that mediate electrical conduction between cells.
27 Capacitance level of membrane (ability to store charge), and resistance of gap junctions/connexons
between cells.
28 Around 0.1m/s in atria, 0.05 in AVN and 4m/s in Bundle of His, mainly need to know that AVN is much
slower.

4. 16.What is the effect of Wolf Parkinson White?29
17.Why is noradrenaline described as a positive inotrope?30
18.What happens if you lose the SAN?31
19.Describe the mechanism of ‘calcium induced calcium release’32
20.What causes repolarisation?33
21.Which channel removes calcium from the cell between beats?34
22.What would happen to HR if you blocked Na+/K+ATPase (e.g. Digoxin)?35
23.What is the mechanism of B receptor agonists increasing cardiac contractility
(e.g. isoprenaline, adrenaline)?36
24.What inhibits the mechanism in (23)?37
Electrocardiogram
1.Which lead is normally looked at to obtain a basic (4 lead) ECG?38
29 Extremely high heart rate because of accessory route of conduction (like an extra AVN)
30 It stimulates Ca2+ entry by acting on B1 receptors, causes increased level of cAMP which increases force
of contraction.
31 The heart will continue to beat but the rate will be slower. Under normal circumstances the fastest
transmission wins which is the SAN
32 Calcium released initially from T-tubule lumen activates calcium channels on the sarcoplasmic reticulum.
These greatly increase Ca2+ further leading to rapid upstroke.
33 K+ efflux as well as SRCA (Sarcoplasmic Reticulum Calcium ATPase) removes Ca2+ from cytosol back
into SR, this process is accelerated by noradrenaline (which also stimulates Ca2+ re-entry) because it
increases the speed/frequency of APs and so increases the heart rate.
34 Na/Ca anti-port, 3Na+(in)/Ca2+(out)
35 Digoxin blocks Na+(out)/K+(in)ATPase in cardiac muscle, which has a knock-on effect on Na+(in)/Ca+
(out) channels because the cell becomes saturated with Na+. Less Ca2+ leaves the cell meaning the AP is
extended and the length of action potential (and so cardiac force) is increased.
36 Increase cyclic AMP which causes more Ca2+ to enter cell, increasing contractility. (cardiac glycosides
such as Digoxin work in the same way).
37 Parasympathetic stimulation and release of acetylcholine (despite being the main neurotransmitter in the
body and having an excitatory effect on striated muscle, acetylcholine has an inhibitory effect on the heart)
38 Lead II

5. 2.What are the approximate lengths of P-R interval, QRS complex and Q-T interval?
39
3.What do the P-R interval and QRS complex represent?40
4. What could a long QRS complex indicate?41
5. What does the ST/QT segment represent?42
6. Why does the ECG trace not remain peaked for the whole time the ventricles are
contacted?43
7. What is the purpose of the right leg lead (4th lead) on a 3 lead ECG?44
8. Where are the 3 leads attached on the body on a 3 lead ECG(each lead is
attached to 2 places on the body)?45
9. Why does the T wave (repolarisation) appear on the same side of the line as the
QRS complex (depolarisation)?46
10.What could an inverted T wave indicate?47
11.What is a vector?48
12.What are the 3 types of leads on a 12 lead ECG and what are the main
differences between these leads?49
39 P-R interval 120ms, QRS complex 80ms and Q-T interval 300ms
40 P-R is the delay in the AV node between atrial depolarisation and ventricular depolarisation, QRS complex
is the time taken for the wave of depolarisation to activate all ventricular muscle.
41 Delays going from one bit of the ventricle to another (e.g. damage to ventricular muscle)
42 The space between ST and QT segments is approximately the plateau of the AP
43 An ECG trace only measures the difference in voltage between different parts of the heart, so it only
produces a trace when there is a difference in voltage, during movement.
44 Earth wire - gets rid of electrical noise on the trace
45 Lead 1 = right arm and left arm, lead 2 = right arm and left leg, lead 3 = left arm and left leg
46 Endocardium (inside) has a longer action potential than the epicardium (outside), so whilst depolarisation
goes from inside-out, repolarisation goes in the reverse direction outside-in.
47 current or recent ischemia
48 A line which has both amplitude and direction (like an ECG incorporates the height + the side of the flat
line)
49 3 bipolar limb leads, 3 augmented unipolar limb leads, 6 horizontal unipolar limb leads. In bipolar leads
both ends are sensing and in unipolar leads only one is sensing and one is an estimate (e.g. what voltage is
likely to be midway between arm and leg).

6. 13.What do AVR,AVL and AVF mean?50
14.Why would a septum which contracted after the ventricles be a problem?51
15.What is 1st degree heart block?52
16.What is 2nd degree heart block?53
17.What is 3rd degree heart block?54
18.What is left bundle branch block?55
19.What is ST elevation or depression and what does it indicate?56
20.What does a long QT interval tell you?57
21.What is hypertrophic cardiomyopathy?58
Haemopoesis and Types of RBC
1. What % of blood would you expect to be haemocrit?59
50 Augmented leads which look at different angles of the ʻtriangleʼ, (AVR - augmented right arm), (AVL -
augmented left arm, AVF - augmented left leg (think ʻfootʼ))
51 Septum needs to contract first so blood can be pushed out effectively, septum contracting onto already
contracted ventricles is a weaker force than ventricles.
52 Where conduction is very slow through the AV node. Shows as a wide P-R interval (distance between
beats). Can be caused by drugs or excessive parasympathetic stimulation.
53 Where SAN is beating at normal rhythm but only around 1/2 or 1/3 beats getting through the AV node. You
will see some additional P waves not conducting through into a QRS complex.
54 Where no signal is getting through the AV node at all. The AV node has been completely destroyed. The
heart will still beat but beats will originate in the ventricles and work at a completely different rate than the
atria (i.e. slower) so the P waves and the QRS complex will be out of sync.
55 Slow route to left ventricle so results in a long QRS. Often follows MI.
56 A competing current is present following recent MI or ischemia because conduction is malfunctioned but
tissue is not dead yet.
57 QT interval represents the time the ventricle is contracted before repolarisation, a long QT means heart
rate is slow. Can be a sign of long QT syndrome (a 1/500 congenital disorder).
58 An enlarged left ventricle, can be the cause of sudden death in otherwise healthy individuals.
59 45% in a male, 35% in a female (roughly)

7. 2. What are granulocytes and agranulocytes and what proportion of white blood
cells are they?60
3. Why are red blood cells shaped in a bi-concave disk?61
4. What is the lifespan of a red blood cell?62
5. How does a normoblast differ from a reticulocyte?63
6. What could cause a low platelet count and how would you visibly notice this?64
7. What colour would reticulocytes stain histologically?65
8. What are alpha granules and dense granules?66
9. What is the average platelet lifespan?67
10.What are megakaryocytes?68
11.What do the 3 different granules in neutrophils contain?69
12.What property do neutrophils have that allows them to survive in hypoxic or
dead tissue?70
60 The two groups of white blood cell, agranulocytes have a non-lobed nucleus (includes neutrophils 40-70%,
eosinophils (1-6%) basophils (less than 1%) and granulocytes have a lobed nucleus (includes lymphocytes
20-40% and monocytes 2-6%).
61 Allows them to have +20-30% surface area compared to a sphere of similar volume and to squeeze and
deform through capillaries
62 Around 120 days, old ones removed by liver and spleen
63 Normoblast = last stage of development of a red blood cell, still has a few mitochondria and ribosomes
which will be lost when the cell becomes a reticulocyte (mature red blood cell)
64 Low platelet count causes spontaneous bruising, could be a result of disturbed marrow function or
chemotherapy having destroyed marrow and platelet production.
65 Cresyl blue and remaining RNA form blue precipitate
66 Both are granules found in platelets. Alpha contain various clotting factors including factor 4 and platelet
derived growth factor whereas dense granules contain seratonin
67 8-10 days
68 Giant cells with large multi-lobed nuclei whose ER vesicles eject cytoplasm surrounded by membrane
which become platelets
69 1 - acid hydrolases (for breakdown of decaying matter), myelopepsidase. 2 - inflammatory mediators
which attract white cells, 3 - gelatinase (denatured collagen), helpful to break through basement membrane
and putting in adhesion proteins into membrane allowing cells to bind (e.g. to vessel endothelium)
70 Have few mitochondria and most respiration is anaerobic

8. 13.How do eosinophils attack larger cells?71
14.What causes degranulation in basophils?72
15.What are the main functions and properties of monocytes?73
16.What is the difference between B lymphocytes and T lymphocytes?74
17.Where does haemopoesis (blood formation) take place in the embryo at (i) 2.5
weeks, (ii) 5 weeks, (iii) 4 months +75
18.What do pluripotent stem cells (precursor cells) require to transform them into
red blood cells?76
Haemeostasis
1. What is primary haemostasis?77
2. What activates platelets by increasing their Ca2+ levels causing them to release
cyclo-oxygenase?78
3. What does cyclo-oxygenase do after this?79
4. What is adhesion?80
71 Contain hydrolytic lysosomal enzymes such as peroxidase, which punch holes in larger cells and help
break through the basal membrane and kill the cell.
72 Basophils and mast cells degranulate when the IgEs they are coated in couple with variable region on
antibody complex
73 Monocytes are highly phagocytic and motile, have a very long lifespan, function is also antigen
presentation and cytokine secretion.
74 B lymphocytes have a surface antibody receptor (for antigens) which cause expansion of the cell and
secretion of more antibody. T lymphocytes are cell mediated (only work by directly touching other cells, CD4
express antigen and CD8 kill the complex formed).
75 2.5 weeks = ʻblood islandsʼ, 5 weeks-4months = liver, 4 months+ = bone marrow
76 IL3 and Stem cell factor
77 Where damage to the endothelium sets of a local mechanism causing
78 Von Willebrand factor (a.k.a. GP1b) released from damage to endothelium
79 Causes the release of thromboxane A (TXA2)
80 Where platelets have bound to each other or the endothelium on all 3 possible binding sites (Von
Willebrand, GP1V and Integrin a2b1). This is the initial stage of blood clot formation

9. 5. What does thromboxane A (TXA2) do?81
6. What is the effect of ADP released from dense granules on blood clotting?82
7. What is the name of the molecules which bridge the gap between platelets?83
8. What is aggregation?84
9. What substances inhibit platelet aggregation?85
10.After the platelets have been joined to the endothelium and to each other, what
substance reinforces the clot structure?86
11.Which enzyme converts soluble fibrinogen into insoluble strands of fibrin?87
12.Which factor converts pro-thrombin to thrombin?88
13.What are the two main functions of thrombin?89
14.Where are the majority of tissue factors produced?90
15.Whereabouts in the cardiovascular system are tissue factor bearing cells (such as
fibroblasts and monoblasts, which start clotting cascade) found?91
81 Release stimulated by cyclo-oxygenase. TXA2 causes release of dense granules from platelets which
contain seratonin and more VWF, ADP and factor 5. TXA2 and seratonin are local vasoconstrictors which act
to limit blood loss by constricting affected vessel.
82 ADP binds to P2Y12 receptors and activates GPIIb and GPIIIa receptors on platelet which bind to
fibrinogen
83 Fibrinogen
84 The process of joining platelets together with fibrin to form an advanced blood clot
85 NO and prostacyclin (vasodilators) because they increase cAMP and cGMP inside the cell. Also tissue
factor pathway inhibitor (TFPI) which binds F10 inhibiting F10-F7 complex
86 Fibrin (derived from fibrinogen)
87 Thrombin
88 Factor VII activates Factor X which combines with Factor V to produce prothrombinase, an enzyme which
converts prothrombin (precursor) into thrombin (enzyme)
89 1/ convert fibrinogen into fibrin, 2/ to form additional cross bridges between platelets in clot to make it hard
and insoluble
90 In the liver
91 Behind the endothelium, so when the endothelium becomes damaged these cells are exposed to platelets
in the blood and the clotting process begins

10. 16.What does tenase do?92
17.What causes the retraction of the clot?93
18.What is activated by heparans on endothelial cells, and the drug heparin, to
inactivate factors 9-12?94
19.Under normal circumstances (i.e. when there is no damage to the endothelium),
what is activated to inhibit factors 5 and 8 and prevent the clotting process?95
20.And in the case of haemostasis, what stops this from happening?96
21.How does aspirin act to inhibit the clotting process?97
22.How does heparin act to inhibit the clotting process?98
23.Why is fondaparinux used as an alternative to heparin?99
24.How does warfarin act to inhibit the clotting process?100
25.What are the 3 parts ofVirchow’s triad of causes of clotting?101
26.What is the visible difference between an arterial thrombus and a venous
thrombus?102
92 Activates factor 10, tenase is activated by combination of factors 8 and 9
93 When Fibrin polymerises into long threads which are cross linked by F13. The clot becomes hardened and
insoluble
94 Antithrombin
95 Active Protein C in complex with Protein S, activated by thrombomodulin, prevents the conversion of
fibrinogen into fibrin
96 Protein C via plasminogen activator inhibitor
97 Aspirin irreversibly inhibits cyclo-oxygenase (which if not inhibited causes the release of ADH, TXA2 and
Seratonin from dense granules)
98 Heparin activates antithrombin which inhibits factors 9-12
99 Because it is a synthetic polysaccharide as opposed to heparin which is animal-derived and has more
negative side effects in terms of immune reactions.
100 inhibits vitamin K reductase which is required for factors to dock with phospholipids on the cell surface.
Takes longer to have an effect than other anticoagulants. Requires regular checking because doses vary
hugely for different people.
101 Endothelial vascular damage (to arteries), low blood flow or stasis in veins and hyper-coagulability
102 Arterial = characterised by lots of platelets so appears white, veins have a higher coagulability because of
slower flow which means the clot captures more red blood cells and appears red. Arterial clots are
associated with atherosclerosis whilst venous ones from immobility e.g. DVT on a plane

11. 27.How would a white clot be treated?103
28.Give 5 examples of clotting diseases?104
Microcirculation and Capillary Dynamics
1. Which areas of the cardiovascular system count as microcirculation?105
2. What are the functions of lymphatic capillaries?106
3. What are the 3 types of capillary?107
4. What are the routes in and out of the continuous capillaries?108
5. What is the glycocalyx?109
6. How is the blood brain barrier different from other capillaries?110
7. How many litres of fluid are pumped through the capillaries per day, and how
much moves across membranes in both directions?111
103 With quick action anticoagulants e.g. aspirin, clopidogrel or by an angioplasty procedure (PCI/stent)
104 Haemophilia A or B, Vitamin K deficiency (uses clotting factors to synthesise vitamin K), Antiphospholipid
syndrome, Von Willebrand Disease (deficiency of VWF), Factor V Leiden (mutant factor 5 cannot be
inactivated by APC so results in hyper-coagulability)
105 Terminal arterioles (which act as ʻsphinctersʼ when they constrict to reduce flow to adjacent capillaries),
Capillaries and Venules (not arteries or arterioles)
106 absorb fluid and protein and return these to the blood via the thoracic duct, take up foreign micro-
organisms from the blood and transport these to the lymph nodes where they can be killed
107 Continuous (main type, present in most tissues and has a monolayer of endothelium, tight junctions and
is the least permeable), Fenestrated (has slightly porous endothelium so is more permeable, found in
glomerular filter), Sinusoid (the most permeable because it has big gaps in the endothelium, found in liver
because it allows large molecules to diffuse in and out)
108 Tight junctions for moderate sized molecules and diffusion of small molecules and transport in vesicles for
anything large like proteins. 90% of water travels through tight junctions and 10% through ʻwater channelsʼ in
the bilayer. Gasses are liphophobic and can therefore dissolve in lipid which can easily diffuse membrane,
small solutes are liphphobic and must travel through the tight junctions (since the cell wall is a lipid bilayer).
109 A layer that coats the whole lumenal (inside) side of the capillary endothelium. It is a negatively charged
gel which acts as a molecular filter for the capillary epithelium
110 The blood brain barrier prevents the diffusion of most hydrophilic solutes (e.g. proteins). Some key
substances (salt, glucose, amino acids) have to go through specific transport proteins. So the composition of
the CSF is tightly regulated.
111 4000L pumped per day but 80,000L travels across the membrane in both directions, the net loss is only
8L/day which is mostly returned to the blood through the lymph. If these pressures are imbalanced, edema of
the tissues will result.

12. 8. What is the approximate pressure gradient out at the arterial end of a capillary,
and in at the venous end?112
9. What is the main gradient driving water into the capillaries?113
10.What is Starling’s equation?114
11.What is the reflection coefficient of a substance?115
12.Why does net movement of fluid differ for different areas of the body?116
13.What might make fluid movement out of the capillary (filtration) lower than
normal for a given area?117
14.Which vein does lymph ultimately drain into?118
15.What drives lymph flow?119
16.What could cause edema to develop?120
17.What is Kwashiakoor?121
18.What is Elephantiasis?122
112 Arterial 40mmHg, venous -15mmHg
113 Capillaries tend to contain more protein than tissues around them so draw water in with osmotic gradient.
Proteins with a high reflection coefficient (e.g. blood protein albumin) tend to exert a higher osmotic pressure
114 Illustrates the role of hydrostatic and oncotic pressures on movement of a fluid across a capillary
membrane. It is ʻMovement of fluid proportional to (capillary pressure - interstitial pressure) - refraction
coefficient (capillary oncotic pressure - interstitial oncotic pressure)ʼ.
115 A measure of the oncotic pressure exerted by a unit of a particular solute
116 Varies for differing pressures according to gravity (e.g. higher pressure in legs/feet therefore more likely to
see edema in legs), also type of capillaries (e.g. fenestrated capillaries in glomerulus, net movement out)
117 If arteriole leading to capillary was constricted (e.g. afferent arteriole), osmotic gradient of interstitial fluid
surrounding capillary, control of permeability by glycocalyx
118 Lymph flows to thoracic duct and then into subclavian vein
119 Fluid forced into lymph and moved along by muscle contraction, valves prevent backflow
120 Blocked lymph nodes due to inflammation, decrease in oncotic pressure of blood, increase in capillary
hydrostatic pressure gradient, hypervolemia.
121 Edema development because of protein malnutrition therefore decreased oncotic gradient in blood and
loss of fluid from the blood. Presents as bloating and edema particularly in abdomen.
122 Where a worm gets into the lymph and blocks lymph vessels causing gross swelling as lymphatics unable
to remove fluid. The same effect may also happen if areas of lymph are surgically removed.

13. Infarction and Embolism
1. Why are most infarcts arterial rather than venous?123
2. What is the difference between a ‘white infarct’ and a ‘red infarct’?124
3. Where are white infarcts most likely to occur?125
4. What is a transmural infarct?126
5. Name the 3 main coronary arteries?127
6. What is a sub-endocardial infarct?128
7. What is the most obvious histological change in necrotic tissue?129
8. What ECG changes would you typically see following an MI: (i) 1-8 hours post MI,
(ii) 8hours-2days post, (iii) more than 2 days post?130
9. What enzymes might you notice in raised levels in the plasma following MI?131
10.What are the two main agents (drugs) associated with thrombolysis?132
11.What is the difference between a thrombus and an embolism?133
123 Because there is usually only one artery supplying a given area of tissue whereas veins more frequently
anastemose.
124 White infarct from arterial occlusion and show up white because of lack of blood cells in region. Red
infarct is the opposite (e.g. pulmonary infarct) where blood has become trapped in necrotic tissue and not
been able to leave (e.g. venous infarct).
125 In solid tissues e.g. heart, spleen, liver which are supplied by a single artery prone to blockage
126 Distribution of infarct over close to 100% of whole area supplied by blocked artery (not 100% because
gas exchange may occur by diffusion at peripheries).
127 Left anterior descending, left circumflex, right coronary
128 Where only the inner 1/3 or 1/2 of ventricular wall is ischemic following infarct.
129 Cells lose their nucleus
130 1-8 hours, ST segment elevation, 8h-2days Q wave increased, over 2 days T wave inversion. May notice
other arrhythmias for 1-2 days post caused by re-entry in dead heart tissue.
131 Cardiac troponins, creatinine kinase
132 Streptokinase and Tissue Plasminogen Factor (TPA)
133 Thrombus has not moved, embolism has moved (embolus, e.g. clotting in legs and goes to lungs or brain)

14. 12.What is commonly responsible for development of thromboembolism in an
atherosclerosed artery?134
13.What is hyperkinesis?135
14.How would you identify a fat embolism histologically?136
15.Which are the two leg veins most likely to produce a DVT resulting in fatal
pulmonary embolism?137
16.What class of drugs would you use to treat ‘white’ thrombi and what for ‘red’
thrombi?138
Pharmacology: Angina
1. What is angina and why does it occur?139
2. What is the difference between unstable angina and vasospastic angina?140
3. What are the main physiological targets of treatment for angina?141
4. What kind of drugs might be given to induce these effects in answer to (3) and
what are their effects?142
134 Rupture of atherosclerotic plaque, release of TXA2, fibrinogen, 5 hydroxytriptamine, platelet activating
factor, adenosine diphosphate which promote platelet aggregation
135 When contractility in the remaining myocardium increases following infarction
136 Use Oil Red O to make the fat more visible
137 Iliac and femoral veins
138 White are platelet rich and are treated with antiplatelet drugs (e.g. Aspirin, Clopidogrel) and red, RBC rich
thrombi are treated with anticoagulants (e.g. Heparin, or Warfarin (for long term)).
139 Pain coming from the heart via nerves in the chest, arm or elsewhere. Occurs when the O2 demand of
the heart is above supply.
140 Unstable angina is due to non-occlusive thrombus i.e. doesnʼt block artery fully whereas vasospastic
angina is the spasm of coronary artery which has probably got atherosclerosis leading to poor perfusion
141 1/ Decreasing the oxygen need of the heart (decreasing cardiac work), 2/ Dilation of the coronary arteries,
3/Decreasing heart rate
142 B-blockers such as propanolol (non-selective) or atenolol (B1 selective) will decrease heart rate and
contractility, GTN spray (Glyceryl trinitrate) which relaxes smooth muscle cells and produces nitric oxide in
presence of ALDH-2, Ivabradine which inhibits ʻIfʼ (which determines pacemaker potential in the SAN) so
decreases heart rate

15. 5. What is the mechanism of nitric oxide in causing vasodilation?143
6. What are the possible negative effects of GTN?144
7. What defines a drug as having 1st pass metabolism?145
8. How long does GTN spray take to produce an effect and how long does this last?
146
9. If you wanted to give nitrates over a longer period than GTN spray what might
you use?147
10.What are reactive oxygen species and what do they do?148
11.How do Ca2+ channel blockers help protect against heart damage?149
12.Name 2 Ca2+ channel blockers150
13.What is a dangerous side effect associated with using Ca2+ channel blockers?151
14.What effect would a K+ channel agonist have on cardiac action potentials?152
143 Normally calcium/calmodulin stimulates release of nitric oxide synthase which catalyses the production of
nitric oxide from L-arginine and NADPH, nitric oxide then stimulates conversion of GMP to cGMP in the
presence of guanate cyclase. Increased cGMP decreases the Ca2+ level and decreases SM contraction. (In
the case of GTN treatment, the GTN is metabolised by ALDH-2 to release NO)
144 headache, red face (dilation), fainting (also from dilation and decreased CO)
145 It cannot be given orally because it is totally metabolised by the liver and so to have an effect is usually
taken sublingually (under tongue) so absorbed into bloodstream, or by spray so absorbed in lungs.
146 1-2 mins for effect, lasts 30 mins
147 GTN patch or isorbide di-nitrate, although the risk is that if administered over an extended period that that
the body develops tolerance to GTN
148 ROS are given off during oxidative stress (e.g. after UV exposure or MI), they cause generalized cell
damage and inhibit ALDH-2 so GTN cannot produce NO as effectively if given after an MI.
149 Ca2+ channel blockers decrease the height of the action potential and so the force of contraction in
cardiac muscle, they also reduce the contraction of SM in veins and arteries (so decrease TPR) and
therefore the O2 demand of the heart.
150 Verapamil or diltiazem
151 Reflex tachycardia (fast heart rate) induced by the relaxation of the heart
152 K+ controls the resting potential of the AP, blocking it would lengthen the action potential by
hyperpolarising the cell but in doing so would decrease the heart rate, reducing cardiac work overall.

16. 15.What would you use to treat vasospastic angina and why would you not use
atenolol?153
16.What is the mechanism of statins given to reduce LDL cholesterol?154
17.What negative side effects may be associated with statins?155
Pharmacology: Anti-Thrombosis Drugs and MI
1. What are the main causes of thrombus?156
2. What is the main type of drug used to treat venous thrombi?157
3. What anti-thrombolytic treatment would be used for rapid effect?158
4. What is the main dangerous side effect of all anticoagulants such as heparin,
warfarin and clopidogrel?159
5. By what mechanism does warfarin inhibit blood clotting?160
6. What is fondaparineux?161
7. What are hirudin and bivalirudin?162
153 Atenolol works on B1 receptors which affect HR and contractility, they have no vascular effect. You would
use vasodilators such as Ca2+ channel blockers or GTN
154 Block liver synthesis of LDL cholesterol by inhibiting hydroxymethyl glutaryl CoA reductase (HMG-CoA).
Liver also takes up more LDL cholesterol from plasma so the level in blood plasma drops.
155 Muscle breakdown and liver damage
156 Atherosclerosis or lack of movement leading to slow blood flow, injury to vessel wall or hyper-coagulability
of blood (drug, congenital)
157 Anticoagulants which cause antithrombin and active clotting factors IIa, IXa and IIIa to form aggregate
complexes which are inactive.
158 Heparin given as IV bolus (as not absorbed orally), acts within a few minutes inhibiting numerous clotting
factors. Disadvantage is unpredictable dose-response.
159 Hemorrhage. This is why all warfarin patients have to regularly attend INR clinics.
160 It blocks the regeneration of Vitamin K (NADH--> NAD+). Less vitamin K is produced which is normally
used in carboxylation of factors II, VII, IX and X so that they can bind calcium and produce a blood clot. If
vitamin K is absent, these factors are still produced by they are unable to bind calcium.
161 A low molecular weight heparin which acts by inhibiting factor Xa, increasing the effect of antithrombin.
Given IV but more predictable than heparin so preferred.
162 Direct thrombin inhibitors, similar to substances found in vampire bats

17. 8. What is the mechanism of aspirin?163
9. What is the mechanism of PY12 inhibitors?164
10.What is the mechanism of GpIIb/IIIa receptor inhibitors?165
11.What are fibrinolytic/thrombolytic drugs and how do they work?166
12.What might an elevated ST segment on an ECG indicate?167
13.Within what length of time would you need to implant a PCI/stent in a patient’s
coronary artery if there was a blockage that had lead to MI?168
Pharmacology: Arrhythmias
1. What are the main causes of atrial fibrillation?169
2. What are the ranges for bradycardia (low heart rate) and tachycardia (high)170
3. What is the difference between a supra-ventricular (SVT) and a ventricular
arrhythmia (VT)?171
4. Give 2 examples of SVT andVT and how they might be identified on an ECG?172
5. What is a latent or ectopic pacemaker?173
163 Aspirin irreversibly inhibits cyclo-oxygenase so blocks synthesis of TXA2 and PGI2
164 Block ADP binding to platelet receptors, so stop activation of platelets by ADP released from dense
granules
165 Platelets are activated by do not adhere to each other and the endothelium as well.
166 Break down fibrin so break up the actual clot itself. Work by promoting the formation of plasmin which
degrades fibrin clots.
167 ST segment is between depolarisation and repolarisation so length of AP, can indicate myocardial
ischaemia as heart is having to work harder (longer contraction).
168 1-6 hours for best results, survival rate decreases rapidly after 1 hour.
169 Atrial dilatation, heart failure, hypertension, overactive thyroid
170 Low = below 60bpm, High = above 100 bpm
171 Supraventricular = origin in or above AV node. Ventricular = origin in ventricle, purkinje fibres or bundle of
His.
172 SVT = Atrial flutter (P waves and QRS dissociated), Atrial Fibrillation - irregular beat and no P.waves, VT
= Ventricular Tachycardia (no organised electrical activity), Ventricular fibrilation = (wide and abnormal QRS,
100-200 bpm)
173 When an area of the heart other than the SAN starts producing a beat, i.e. has the fastest action potential
and sets the heart rate.

18. 6. What produces an ectopic beat?174
7. What is triggered automaticity?175
8. What is re-entry and where is it likely to occur?176
9. What is Wolff Parkinson White syndrome?177
10.What are the 4 classes of anti-arrhythmic drugs?178
11.What are the mechanisms by which adenosine and digoxin take effect on the
heart?179
12.How do Na+ channel blockers such as the local anesthetic lidnocane reduce the
heart rate?180
13.What causes the tendency of some parts of the heart to become pacemakers in
the case of ischaemia?181
14.What is a radiofrequency ablation?182
Physiopathology of Heart Failure
174 Where localised low plasma K+ causes decreased diastolic potential (does not effectively repolarise), so
the threshold potential for Ca2+ channels is reached sooner and causes production of ectopic beat. Often
triggered by ischaemia.
175 Excessive increases in Ca2+, often drug induced, trigger premature APs
176 Where an impulse becomes ʻtrappedʼ in a loop around one region of the heart. Stimulates the tissue
adjacent to it causing it to beat prematurely. Often occurs in damaged tissue around the edge of an infarct.
177 The presence of an additional pathway other than the AVN known as the Bundle of Kent which allows
APs from the atria to the ventricles, causes a competing potential and arrhythmia. It is detected in the
presence of a pre-excitation delta wave and can speed up the heart rate.
178 Class 1 = Na+ channel blockers (lidnocane), Class 2 = B receptor blockers (propanolol), Class 3 = AP
Prolonging drugs (amiodarone), Class 4 = Ca2+ channel (verapamil)
179 Both slow AVN conduction whilst digoxin increases vagal activity so slows AV node conduction. They can
also be used to block the isthmus (extra-channel) in re-entry.
180 Blocking the Na+ channel means conduction can only operate on Ca2+ so it raises the threshold for AP
firing.
181 Ischaemia causes increased noradrenaline release which increases Ca2+ in cardiac cells, the heart has
more of a tendency to depolarise under these conditions and one part may end up depolarising faster than
the SAN. Noradrenaline and catecholamine also speeds up AVN conduction.
182 Medical procedure where re-entrant tissue pathway is destroyed to limit

19. 1. What is the definition of heart failure?183
2. What is decompensation?184
3. Define ‘after-load’ and ‘preload’?185
4. What does angiotensin do to the preload?186
5. What is often the cause of right heart failure?187
6. What does an S3 S4 gallop indicate?188
7. What is ‘pitting’?189
8. What is ascites?190
9. Explain the difference between hypertrophy and hyperplasia?191
10.Why would the right ventricle take on a larger volume for a given EDP than the
left ventricle at the same EDP?192
11.Why might a distended right heart not indicate right heart failure?193
183 Inability to provide adequate cardiac output to support the needs of the tissues
184 When eventually, in spite or because of compensatory mechanisms, heart failure is such that
CO and BP begin to fall. Little things like stress or flu can set this off.
185 Afterload = tension developed in left ventricular wall during systole, Preload = the initial stretching of the
left ventricle prior to contraction (i.e. sarcomere length prior to contraction), reflects filling volume.
186 Increases load on the heart by vasoconstriction, and increases blood volume so increases preload
187 Can occur in chronic pulmonary conditions where the right heart is having to work harder to pump blood
to the lungs, right heart ultimately fails due to pressure overload. OR in congestive heart failure the right
heart is having to work harder to support a failing left heart.
188 S3 is the blood rushing into the ventricles from the atria, S4 is caused by the atria forcefully contracting to
fill an abnormally stiff hypertrophic ventricle. S3-S4 gallop indicates a high filling pressure.
189 Severe edema where pressing into the skin creates a ʻpitʼ like pressing into wet sand
190 edema in the peritoneal area, looks like a bloated belly
191 Hypertrophy is the increase in the size of cells to make the heart dilated/distended. You only have a
certain number of cardiac cells and cannot create more of them. Hyperplasia is an increase in the number of
cells of an organ.
192 Because the right heart has a thinner wall
193 Could have been distended compensating for a failing left heart without failing itself

20. 12.What are typical hydrostatic pressures for the pulmonary vein and pulmonary
artery?194
13.What causes muscle weakness and generalized weakness in heart failure?195
14.Why do mechanisms for increasing cardiac output during exercise not function
properly in a failing heart?196
15.How would increased muscle mass (cardiac hypertrophy) appear on an ECG?197
16.What is the difference between a dilated heart and cardiac hypertrophy?198
Treatment of Heart Failure
1. What are the possible adverse effects of using ACE 1 inhibitors?199
2. Why would you use Angiotensin II receptor blockers instead of Angiotensin I
receptor blockers?200
3. What positive effect might using diuretics have on the respiratory system?201
4. What are the negative side effects on cardiac function can be caused by thiazide
and loop diuretics?202
5. What could you do to reduce this effect?203
194 Vein 10mmHg, Artery 20mmHg
195 Not enough blood perfusing tissues because of failing heart but also because the compensatory
mechanisms making up for failing heart constrict the arteries to skeletal muscle in an attempt to divert blood
flow to the heart.
196 Because the heart is already compensating in this way, it is working at maximum output or even
decompensating. It also becomes less sensitive to noradrenaline.
197 Rightward shift of cardiac index
198 In both cases the heart will appear ʻbiggerʼ but in hypertrophy this is because the cells are bigger and
there is more muscle mass, in a dilated heart the wall has been stretched so much that it is actually thinner.
199 Hypotension, Renal Impairment (because angiotensin normally controls differential constriction of the
afferent and efferent arterials – if this is taken away GFR can rise or fall to damaging levels), Hyperkalemia
(because you’re not excreting enough K+)
200 Normally Bradykinin is broken down by ACE, ACE is active during the step between Ang 1 and Ang 2 so it
is less active when Angiotensin 1 blockers are used. Angiotensin 2 blockers have no effect on bradykinin
levels.
201 Increase exercise capability by reducing dyspnoea (breathlessness/pulmonary edema)
202 Excessive K+ loss leading to slower repolarisation and resulting arrhythmias
203 Give a K+ sparing diuretic in addition, spironolactone (aldosterone antagonist) or K+ supplements

21. 6. What are the negative side effects of spironolactone?204
7. What is ivabradine?205
8. What are the main positive effects of B-blockers?206
9. What kind of drugs reduce afterload?207
10.What are cardiac glycosides and what is their mechanism?208
11.Why do cardiac glycosides not prolong survival in heart failure (apart from
causing arrhythmias?209
12.Why might cardiac glycosides cause arrhythmias?210
13.How do B1 agonists work?211
14.What diagnosis would you make of an ejection fraction of (i) less than 45% (ii)
more than 50% (iii) less than 40%212
15.How do PDE inhibitors work?213
Atherosclerosis
1. Name the 4 basic structural layers of a muscular artery?214
204 Gynecomastia, hyperkalaemia (because aldosterone normally causes K+ secretion) and renal
dysfunction
205 An inhibitor of ‘If’ so slows heart rate and stabilises heart, reducing the chance of arrythmias
206 Negative inotropes which reduce cardiac remodelling and rennin release, decrease symptoms of heart
failure
207 Vasorelaxants such as hydralazine and isosorbide dinitrate
208 Increase contractility by inhibiting K+(in)/Na+(out) pumps in cardiac muscle cells. More Na+ in cell
reduces Ca2+ loss because it slows down the Na+(in)/Ca2+(out) pumps.
209 It is a positive inotrope so makes the heart work harder making symptoms worse. They are used to treat
atrial fibrillation because they reduce AVN conduction.
210 Because they increase the excitability of the tissue and may lead to a delayed after polarisation
211 Opposite of beta blockers, they act like noradrenaline and stimulate release of adenylate cyclase which
stimulates cAMP release which increases force and heart rate
212 Less than 45= moderate systolic dysfunction, greater than 50=diastolic dysfunction, less than 40 = severe
systolic dyfunction
213 PDE III mediates the conversion of cAMP into 5-AMP (inactive form) so means cAMP retains its active
form for longer
214 Endothelium, tunica intima, tunica media, tunica adventitia

22. 2. Which parts of the artery structure does atherosclerosis affect?215
3. What is Monchebergʼs Medial Sclerosis?216
4. Describe the stages of formation of a fatty atheromatous plaque (not embolism)217
5. What are vasa vasora?218
6. What is intermittent claudication?219
7. What is the most common location for aneurysm?220
215 Intima and internal elastic lamina
216 Calcification of muscular arteries
217 Lipid crosses endothelium in high levels from blood, phagocytosed by macrophages (monocytes), high
level of lipid present in macrophages in the intima, smooth muscle cells migrate from media to intima, these
are modified under these condition so that they are also able to phagocytose lipid and start producing lipid
rich collagen, collagen plaques then appear white, fatty plaque obscures media (SM) and therefore artery
weaker, less able to constrict but gets blocked by lipid. May lead to aneurysm (abnormal dilatation and
bursting) or embolism (clot).
218 Vessels which supply the adventitia and outer 1/3 of media (literally = ʻvessels of vesselsʼ)
219 Pain in calf muscles when walking, leg arteries narrowed by atherosclerosis and lactic acid builds up.
220 Abdominal aorta