John Palmer’s Chest PainStarling’s Law1. What variables can change cardiac output?12. What are after-load and preload?23. ...
10.What does an increase in blood volume do to CVP and CO?1011.What effects does digoxin have on the heart and venous syst...
7. How is conduction of a cardiac action potential slowed by the AV node?208. What is the Ca2+ threshold (i.e. voltage at ...
16.What is the effect of Wolf Parkinson White?2917.Why is noradrenaline described as a positive inotrope?3018.What happens...
2.What are the approximate lengths of P-R interval, QRS complex and Q-T interval?393.What do the P-R interval and QRS comp...
13.What do AVR,AVL and AVF mean?5014.Why would a septum which contracted after the ventricles be a problem?5115.What is 1s...
2. What are granulocytes and agranulocytes and what proportion of white bloodcells are they?603. Why are red blood cells s...
13.How do eosinophils attack larger cells?7114.What causes degranulation in basophils?7215.What are the main functions and...
5. What does thromboxane A (TXA2) do?816. What is the effect of ADP released from dense granules on blood clotting?827. Wh...
16.What does tenase do?9217.What causes the retraction of the clot?9318.What is activated by heparans on endothelial cells...
27.How would a white clot be treated?10328.Give 5 examples of clotting diseases?104Microcirculation and Capillary Dynamics...
8. What is the approximate pressure gradient out at the arterial end of a capillary,and in at the venous end?1129. What is...
Infarction and Embolism1. Why are most infarcts arterial rather than venous?1232. What is the difference between a ‘white ...
12.What is commonly responsible for development of thromboembolism in anatherosclerosed artery?13413.What is hyperkinesis?...
5. What is the mechanism of nitric oxide in causing vasodilation?1436. What are the possible negative effects of GTN?1447....
15.What would you use to treat vasospastic angina and why would you not useatenolol?15316.What is the mechanism of statins...
8. What is the mechanism of aspirin?1639. What is the mechanism of PY12 inhibitors?16410.What is the mechanism of GpIIb/II...
6. What produces an ectopic beat?1747. What is triggered automaticity?1758. What is re-entry and where is it likely to occ...
1. What is the definition of heart failure?1832. What is decompensation?1843. Define ‘after-load’ and ‘preload’?1854. What d...
12.What are typical hydrostatic pressures for the pulmonary vein and pulmonaryartery?19413.What causes muscle weakness and...
6. What are the negative side effects of spironolactone?2047. What is ivabradine?2058. What are the main positive effects ...
2. Which parts of the artery structure does atherosclerosis affect?2153. What is Monchebergʼs Medial Sclerosis?2164. Descr...
Upcoming SlideShare
Loading in...5
×

Sc03 John palmer's chest pain

766

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
766
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
48
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Transcript of "Sc03 John palmer's chest pain"

  1. 1. John Palmer’s Chest PainStarling’s Law1. What variables can change cardiac output?12. What are after-load and preload?23. What is Starling’s Law?34. What is the main difference between cardiac muscle and skeletal muscle?45. Why is cardiac muscle more sensitive to stretch than skeletal muscle?56. Why is Starling’s Law important?67. Where would you calculate blood pressure in the lungs?78. What happens to stroke work and end diastolic pressure (i) In exercise (ii) inheart failure?89. Why is cardiac output low in a dilated heart?91 Filling pressure of right heart, function of the heart-lung unit (e.g. pulmonary edema?), Resistance tooutflow from left ventricle, Influence of ANS on B1 receptors2 After-load is the tension on the wall of the left ventricle during ejection. Preload is the resistance to outflowfrom 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 themuscle 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 byCa2+ and TnC to expose binding site. Cardiac muscle is made up of intercalated disks, doesnʼt tire likeskeletal muscle and relies on Ca2+ in the cells to maintain a prolonged AP ʻplateauʼ which is not the case inskeletal 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) becomesmore 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 pressure8 In exercise = stroke work and EDP increase because the heart is distended, in heart failure both decreasebecause the heart is grossly distended and has gone beyond optimum stretch potential9 Although more stretch equals more force this is only true to a point. In a grossly distended heart LaplaceʼsLaw (pressure = 2x tension/radius), so a greater radius actually means less pressure.
  2. 2. 10.What does an increase in blood volume do to CVP and CO?1011.What effects does digoxin have on the heart and venous system?1112.How do you work out CO from HR and SV?1213.How do you work out SV from EDV and ESV?13Initiation of the Heart Beat1. What is the equilibrium potential for potassium?142. What are the approximate lengths (in milliseconds) for a nerve AP and a cardiacAP?153. What causes cardiac muscle to contract?164. ... and to relax?175. Which class of anti-arrhythmic drugs (i) block Ca2+ channels, (ii) block K+channels (iii) block Na+ channels?186. Why is there a bigger spike in voltage in an action potential through the Purkinjefibres than in the ventricles?1910 Both increased11 Increases contractility and decreases CVP as more blood pumped into arteries.12 Heart rate (bpm) x stroke volume13 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 muscle15 Nerve (3ms), Cardiac (300ms)16 Na+ channels open, influx of Na+, fast upstroke from -90mv, channels start to close when charge getsnearer to 0mv and when over 0mv, voltage gated L-type Ca2+ channels open which causes a large influx ofCa2+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. 3. 7. How is conduction of a cardiac action potential slowed by the AV node?208. What is the Ca2+ threshold (i.e. voltage at which Ca2+ channels are opened) inthe SAN?219. What do delayed rectifier K+ channels have to do with heart rate?2210.Why is there little inherent decay of K+ in skeletal muscle, whereas there is incardiac muscle?2311.What do ‘If’ channels do?2412.How does parasympathetic stimulation slow the heart rate?2513.How are cardiac muscle cells connected to ensure electrical transmissionbetween them?2614.What factors (outside the cell) might slow the rate of conduction of the wave ofdepolarisation?2715.What is the speed of AP conduction in the atria,AVN and bundle of His?2820 AV node cells do not contain fast upstroke Na+ channels so only depolarize when resting potentialnaturally decay is large enough to be picked up by the Ca2+ channels, upstroke is entirely driven by calciumand 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. Thechannels gradually decay, so K+ enters at a slower rate, meaning RMP can be maintained for a shorterperiod 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 incardiac cells. This is the reason K+ equilibrium potential is reached in cardiac muscle but not skeletalmuscle.24 ʻIfʼ channels control how much Na+ enters the cell, and therefore how much K+ comes out (via basolateralNa+/K+ATPase), so blocking ʻIfʼ blocks decay of action potential because less K+ leaves cell. Sympatheticstimulation causes increased firing of action potentials by increasing activity of If channels, increasing rate ofAP decay and so frequency of APs.25 Blocking K+ channels in the SAN, causing hyperpolarisation and so takes longer for natural decay of APand longer to repolarise.26 Intercalated disks are connected by a desmosome, between these are gap junctions containingʻconnexonsʼ which are channels that mediate electrical conduction between cells.27 Capacitance level of membrane (ability to store charge), and resistance of gap junctions/connexonsbetween 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 muchslower.
  4. 4. 16.What is the effect of Wolf Parkinson White?2917.Why is noradrenaline described as a positive inotrope?3018.What happens if you lose the SAN?3119.Describe the mechanism of ‘calcium induced calcium release’3220.What causes repolarisation?3321.Which channel removes calcium from the cell between beats?3422.What would happen to HR if you blocked Na+/K+ATPase (e.g. Digoxin)?3523.What is the mechanism of B receptor agonists increasing cardiac contractility(e.g. isoprenaline, adrenaline)?3624.What inhibits the mechanism in (23)?37Electrocardiogram1.Which lead is normally looked at to obtain a basic (4 lead) ECG?3829 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 forceof contraction.31 The heart will continue to beat but the rate will be slower. Under normal circumstances the fastesttransmission wins which is the SAN32 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 backinto SR, this process is accelerated by noradrenaline (which also stimulates Ca2+ re-entry) because itincreases 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 isextended 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 glycosidessuch as Digoxin work in the same way).37 Parasympathetic stimulation and release of acetylcholine (despite being the main neurotransmitter in thebody and having an excitatory effect on striated muscle, acetylcholine has an inhibitory effect on the heart)38 Lead II
  5. 5. 2.What are the approximate lengths of P-R interval, QRS complex and Q-T interval?393.What do the P-R interval and QRS complex represent?404. What could a long QRS complex indicate?415. What does the ST/QT segment represent?426. Why does the ECG trace not remain peaked for the whole time the ventricles arecontacted?437. What is the purpose of the right leg lead (4th lead) on a 3 lead ECG?448. Where are the 3 leads attached on the body on a 3 lead ECG(each lead isattached to 2 places on the body)?459. Why does the T wave (repolarisation) appear on the same side of the line as theQRS complex (depolarisation)?4610.What could an inverted T wave indicate?4711.What is a vector?4812.What are the 3 types of leads on a 12 lead ECG and what are the maindifferences between these leads?4939 P-R interval 120ms, QRS complex 80ms and Q-T interval 300ms40 P-R is the delay in the AV node between atrial depolarisation and ventricular depolarisation, QRS complexis 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 AP43 An ECG trace only measures the difference in voltage between different parts of the heart, so it onlyproduces a trace when there is a difference in voltage, during movement.44 Earth wire - gets rid of electrical noise on the trace45 Lead 1 = right arm and left arm, lead 2 = right arm and left leg, lead 3 = left arm and left leg46 Endocardium (inside) has a longer action potential than the epicardium (outside), so whilst depolarisationgoes from inside-out, repolarisation goes in the reverse direction outside-in.47 current or recent ischemia48 A line which has both amplitude and direction (like an ECG incorporates the height + the side of the flatline)49 3 bipolar limb leads, 3 augmented unipolar limb leads, 6 horizontal unipolar limb leads. In bipolar leadsboth ends are sensing and in unipolar leads only one is sensing and one is an estimate (e.g. what voltage islikely to be midway between arm and leg).
  6. 6. 13.What do AVR,AVL and AVF mean?5014.Why would a septum which contracted after the ventricles be a problem?5115.What is 1st degree heart block?5216.What is 2nd degree heart block?5317.What is 3rd degree heart block?5418.What is left bundle branch block?5519.What is ST elevation or depression and what does it indicate?5620.What does a long QT interval tell you?5721.What is hypertrophic cardiomyopathy?58Haemopoesis and Types of RBC1. What % of blood would you expect to be haemocrit?5950 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 alreadycontracted 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 betweenbeats). 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. Youwill 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. Theheart will still beat but beats will originate in the ventricles and work at a completely different rate than theatria (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 buttissue is not dead yet.57 QT interval represents the time the ventricle is contracted before repolarisation, a long QT means heartrate 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. 7. 2. What are granulocytes and agranulocytes and what proportion of white bloodcells are they?603. Why are red blood cells shaped in a bi-concave disk?614. What is the lifespan of a red blood cell?625. How does a normoblast differ from a reticulocyte?636. What could cause a low platelet count and how would you visibly notice this?647. What colour would reticulocytes stain histologically?658. What are alpha granules and dense granules?669. What is the average platelet lifespan?6710.What are megakaryocytes?6811.What do the 3 different granules in neutrophils contain?6912.What property do neutrophils have that allows them to survive in hypoxic ordead tissue?7060 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 lymphocytes20-40% and monocytes 2-6%).61 Allows them to have +20-30% surface area compared to a sphere of similar volume and to squeeze anddeform through capillaries62 Around 120 days, old ones removed by liver and spleen63 Normoblast = last stage of development of a red blood cell, still has a few mitochondria and ribosomeswhich 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 orchemotherapy having destroyed marrow and platelet production.65 Cresyl blue and remaining RNA form blue precipitate66 Both are granules found in platelets. Alpha contain various clotting factors including factor 4 and plateletderived growth factor whereas dense granules contain seratonin67 8-10 days68 Giant cells with large multi-lobed nuclei whose ER vesicles eject cytoplasm surrounded by membranewhich become platelets69 1 - acid hydrolases (for breakdown of decaying matter), myelopepsidase. 2 - inflammatory mediatorswhich attract white cells, 3 - gelatinase (denatured collagen), helpful to break through basement membraneand 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. 8. 13.How do eosinophils attack larger cells?7114.What causes degranulation in basophils?7215.What are the main functions and properties of monocytes?7316.What is the difference between B lymphocytes and T lymphocytes?7417.Where does haemopoesis (blood formation) take place in the embryo at (i) 2.5weeks, (ii) 5 weeks, (iii) 4 months +7518.What do pluripotent stem cells (precursor cells) require to transform them intored blood cells?76Haemeostasis1. What is primary haemostasis?772. What activates platelets by increasing their Ca2+ levels causing them to releasecyclo-oxygenase?783. What does cyclo-oxygenase do after this?794. What is adhesion?8071 Contain hydrolytic lysosomal enzymes such as peroxidase, which punch holes in larger cells and helpbreak 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 onantibody complex73 Monocytes are highly phagocytic and motile, have a very long lifespan, function is also antigenpresentation and cytokine secretion.74 B lymphocytes have a surface antibody receptor (for antigens) which cause expansion of the cell andsecretion of more antibody. T lymphocytes are cell mediated (only work by directly touching other cells, CD4express antigen and CD8 kill the complex formed).75 2.5 weeks = ʻblood islandsʼ, 5 weeks-4months = liver, 4 months+ = bone marrow76 IL3 and Stem cell factor77 Where damage to the endothelium sets of a local mechanism causing78 Von Willebrand factor (a.k.a. GP1b) released from damage to endothelium79 Causes the release of thromboxane A (TXA2)80 Where platelets have bound to each other or the endothelium on all 3 possible binding sites (VonWillebrand, GP1V and Integrin a2b1). This is the initial stage of blood clot formation
  9. 9. 5. What does thromboxane A (TXA2) do?816. What is the effect of ADP released from dense granules on blood clotting?827. What is the name of the molecules which bridge the gap between platelets?838. What is aggregation?849. What substances inhibit platelet aggregation?8510.After the platelets have been joined to the endothelium and to each other, whatsubstance reinforces the clot structure?8611.Which enzyme converts soluble fibrinogen into insoluble strands of fibrin?8712.Which factor converts pro-thrombin to thrombin?8813.What are the two main functions of thrombin?8914.Where are the majority of tissue factors produced?9015.Whereabouts in the cardiovascular system are tissue factor bearing cells (such asfibroblasts and monoblasts, which start clotting cascade) found?9181 Release stimulated by cyclo-oxygenase. TXA2 causes release of dense granules from platelets whichcontain seratonin and more VWF, ADP and factor 5. TXA2 and seratonin are local vasoconstrictors which actto limit blood loss by constricting affected vessel.82 ADP binds to P2Y12 receptors and activates GPIIb and GPIIIa receptors on platelet which bind tofibrinogen83 Fibrinogen84 The process of joining platelets together with fibrin to form an advanced blood clot85 NO and prostacyclin (vasodilators) because they increase cAMP and cGMP inside the cell. Also tissuefactor pathway inhibitor (TFPI) which binds F10 inhibiting F10-F7 complex86 Fibrin (derived from fibrinogen)87 Thrombin88 Factor VII activates Factor X which combines with Factor V to produce prothrombinase, an enzyme whichconverts prothrombin (precursor) into thrombin (enzyme)89 1/ convert fibrinogen into fibrin, 2/ to form additional cross bridges between platelets in clot to make it hardand insoluble90 In the liver91 Behind the endothelium, so when the endothelium becomes damaged these cells are exposed to plateletsin the blood and the clotting process begins
  10. 10. 16.What does tenase do?9217.What causes the retraction of the clot?9318.What is activated by heparans on endothelial cells, and the drug heparin, toinactivate factors 9-12?9419.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?9520.And in the case of haemostasis, what stops this from happening?9621.How does aspirin act to inhibit the clotting process?9722.How does heparin act to inhibit the clotting process?9823.Why is fondaparinux used as an alternative to heparin?9924.How does warfarin act to inhibit the clotting process?10025.What are the 3 parts ofVirchow’s triad of causes of clotting?10126.What is the visible difference between an arterial thrombus and a venousthrombus?10292 Activates factor 10, tenase is activated by combination of factors 8 and 993 When Fibrin polymerises into long threads which are cross linked by F13. The clot becomes hardened andinsoluble94 Antithrombin95 Active Protein C in complex with Protein S, activated by thrombomodulin, prevents the conversion offibrinogen into fibrin96 Protein C via plasminogen activator inhibitor97 Aspirin irreversibly inhibits cyclo-oxygenase (which if not inhibited causes the release of ADH, TXA2 andSeratonin from dense granules)98 Heparin activates antithrombin which inhibits factors 9-1299 Because it is a synthetic polysaccharide as opposed to heparin which is animal-derived and has morenegative 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 varyhugely for different people.101 Endothelial vascular damage (to arteries), low blood flow or stasis in veins and hyper-coagulability102 Arterial = characterised by lots of platelets so appears white, veins have a higher coagulability because ofslower flow which means the clot captures more red blood cells and appears red. Arterial clots areassociated with atherosclerosis whilst venous ones from immobility e.g. DVT on a plane
  11. 11. 27.How would a white clot be treated?10328.Give 5 examples of clotting diseases?104Microcirculation and Capillary Dynamics1. Which areas of the cardiovascular system count as microcirculation?1052. What are the functions of lymphatic capillaries?1063. What are the 3 types of capillary?1074. What are the routes in and out of the continuous capillaries?1085. What is the glycocalyx?1096. How is the blood brain barrier different from other capillaries?1107. How many litres of fluid are pumped through the capillaries per day, and howmuch moves across membranes in both directions?111103 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), Antiphospholipidsyndrome, Von Willebrand Disease (deficiency of VWF), Factor V Leiden (mutant factor 5 cannot beinactivated 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 killed107 Continuous (main type, present in most tissues and has a monolayer of endothelium, tight junctions andis the least permeable), Fenestrated (has slightly porous endothelium so is more permeable, found inglomerular filter), Sinusoid (the most permeable because it has big gaps in the endothelium, found in liverbecause 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 foranything large like proteins. 90% of water travels through tight junctions and 10% through ʻwater channelsʼ inthe 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 chargedgel which acts as a molecular filter for the capillary epithelium110 The blood brain barrier prevents the diffusion of most hydrophilic solutes (e.g. proteins). Some keysubstances (salt, glucose, amino acids) have to go through specific transport proteins. So the composition ofthe CSF is tightly regulated.111 4000L pumped per day but 80,000L travels across the membrane in both directions, the net loss is only8L/day which is mostly returned to the blood through the lymph. If these pressures are imbalanced, edema ofthe tissues will result.
  12. 12. 8. What is the approximate pressure gradient out at the arterial end of a capillary,and in at the venous end?1129. What is the main gradient driving water into the capillaries?11310.What is Starling’s equation?11411.What is the reflection coefficient of a substance?11512.Why does net movement of fluid differ for different areas of the body?11613.What might make fluid movement out of the capillary (filtration) lower thannormal for a given area?11714.Which vein does lymph ultimately drain into?11815.What drives lymph flow?11916.What could cause edema to develop?12017.What is Kwashiakoor?12118.What is Elephantiasis?122112 Arterial 40mmHg, venous -15mmHg113 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 pressure114 Illustrates the role of hydrostatic and oncotic pressures on movement of a fluid across a capillarymembrane. It is ʻMovement of fluid proportional to (capillary pressure - interstitial pressure) - refractioncoefficient (capillary oncotic pressure - interstitial oncotic pressure)ʼ.115 A measure of the oncotic pressure exerted by a unit of a particular solute116 Varies for differing pressures according to gravity (e.g. higher pressure in legs/feet therefore more likely tosee 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 fluidsurrounding capillary, control of permeability by glycocalyx118 Lymph flows to thoracic duct and then into subclavian vein119 Fluid forced into lymph and moved along by muscle contraction, valves prevent backflow120 Blocked lymph nodes due to inflammation, decrease in oncotic pressure of blood, increase in capillaryhydrostatic pressure gradient, hypervolemia.121 Edema development because of protein malnutrition therefore decreased oncotic gradient in blood andloss 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 unableto remove fluid. The same effect may also happen if areas of lymph are surgically removed.
  13. 13. Infarction and Embolism1. Why are most infarcts arterial rather than venous?1232. What is the difference between a ‘white infarct’ and a ‘red infarct’?1243. Where are white infarcts most likely to occur?1254. What is a transmural infarct?1265. Name the 3 main coronary arteries?1276. What is a sub-endocardial infarct?1287. What is the most obvious histological change in necrotic tissue?1298. 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?1309. What enzymes might you notice in raised levels in the plasma following MI?13110.What are the two main agents (drugs) associated with thrombolysis?13211.What is the difference between a thrombus and an embolism?133123 Because there is usually only one artery supplying a given area of tissue whereas veins more frequentlyanastemose.124 White infarct from arterial occlusion and show up white because of lack of blood cells in region. Redinfarct is the opposite (e.g. pulmonary infarct) where blood has become trapped in necrotic tissue and notbeen 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 blockage126 Distribution of infarct over close to 100% of whole area supplied by blocked artery (not 100% becausegas exchange may occur by diffusion at peripheries).127 Left anterior descending, left circumflex, right coronary128 Where only the inner 1/3 or 1/2 of ventricular wall is ischemic following infarct.129 Cells lose their nucleus130 1-8 hours, ST segment elevation, 8h-2days Q wave increased, over 2 days T wave inversion. May noticeother arrhythmias for 1-2 days post caused by re-entry in dead heart tissue.131 Cardiac troponins, creatinine kinase132 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. 14. 12.What is commonly responsible for development of thromboembolism in anatherosclerosed artery?13413.What is hyperkinesis?13514.How would you identify a fat embolism histologically?13615.Which are the two leg veins most likely to produce a DVT resulting in fatalpulmonary embolism?13716.What class of drugs would you use to treat ‘white’ thrombi and what for ‘red’thrombi?138Pharmacology: Angina1. What is angina and why does it occur?1392. What is the difference between unstable angina and vasospastic angina?1403. What are the main physiological targets of treatment for angina?1414. What kind of drugs might be given to induce these effects in answer to (3) andwhat are their effects?142134 Rupture of atherosclerotic plaque, release of TXA2, fibrinogen, 5 hydroxytriptamine, platelet activatingfactor, adenosine diphosphate which promote platelet aggregation135 When contractility in the remaining myocardium increases following infarction136 Use Oil Red O to make the fat more visible137 Iliac and femoral veins138 White are platelet rich and are treated with antiplatelet drugs (e.g. Aspirin, Clopidogrel) and red, RBC richthrombi 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 ofthe heart is above supply.140 Unstable angina is due to non-occlusive thrombus i.e. doesnʼt block artery fully whereas vasospasticangina is the spasm of coronary artery which has probably got atherosclerosis leading to poor perfusion141 1/ Decreasing the oxygen need of the heart (decreasing cardiac work), 2/ Dilation of the coronary arteries,3/Decreasing heart rate142 B-blockers such as propanolol (non-selective) or atenolol (B1 selective) will decrease heart rate andcontractility, GTN spray (Glyceryl trinitrate) which relaxes smooth muscle cells and produces nitric oxide inpresence of ALDH-2, Ivabradine which inhibits ʻIfʼ (which determines pacemaker potential in the SAN) sodecreases heart rate
  15. 15. 5. What is the mechanism of nitric oxide in causing vasodilation?1436. What are the possible negative effects of GTN?1447. What defines a drug as having 1st pass metabolism?1458. How long does GTN spray take to produce an effect and how long does this last?1469. If you wanted to give nitrates over a longer period than GTN spray what mightyou use?14710.What are reactive oxygen species and what do they do?14811.How do Ca2+ channel blockers help protect against heart damage?14912.Name 2 Ca2+ channel blockers15013.What is a dangerous side effect associated with using Ca2+ channel blockers?15114.What effect would a K+ channel agonist have on cardiac action potentials?152143 Normally calcium/calmodulin stimulates release of nitric oxide synthase which catalyses the production ofnitric oxide from L-arginine and NADPH, nitric oxide then stimulates conversion of GMP to cGMP in thepresence of guanate cyclase. Increased cGMP decreases the Ca2+ level and decreases SM contraction. (Inthe 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 usuallytaken sublingually (under tongue) so absorbed into bloodstream, or by spray so absorbed in lungs.146 1-2 mins for effect, lasts 30 mins147 GTN patch or isorbide di-nitrate, although the risk is that if administered over an extended period that thatthe body develops tolerance to GTN148 ROS are given off during oxidative stress (e.g. after UV exposure or MI), they cause generalized celldamage 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 incardiac muscle, they also reduce the contraction of SM in veins and arteries (so decrease TPR) andtherefore the O2 demand of the heart.150 Verapamil or diltiazem151 Reflex tachycardia (fast heart rate) induced by the relaxation of the heart152 K+ controls the resting potential of the AP, blocking it would lengthen the action potential byhyperpolarising the cell but in doing so would decrease the heart rate, reducing cardiac work overall.
  16. 16. 15.What would you use to treat vasospastic angina and why would you not useatenolol?15316.What is the mechanism of statins given to reduce LDL cholesterol?15417.What negative side effects may be associated with statins?155Pharmacology: Anti-Thrombosis Drugs and MI1. What are the main causes of thrombus?1562. What is the main type of drug used to treat venous thrombi?1573. What anti-thrombolytic treatment would be used for rapid effect?1584. What is the main dangerous side effect of all anticoagulants such as heparin,warfarin and clopidogrel?1595. By what mechanism does warfarin inhibit blood clotting?1606. What is fondaparineux?1617. What are hirudin and bivalirudin?162153 Atenolol works on B1 receptors which affect HR and contractility, they have no vascular effect. You woulduse vasodilators such as Ca2+ channel blockers or GTN154 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 damage156 Atherosclerosis or lack of movement leading to slow blood flow, injury to vessel wall or hyper-coagulabilityof blood (drug, congenital)157 Anticoagulants which cause antithrombin and active clotting factors IIa, IXa and IIIa to form aggregatecomplexes which are inactive.158 Heparin given as IV bolus (as not absorbed orally), acts within a few minutes inhibiting numerous clottingfactors. 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 normallyused in carboxylation of factors II, VII, IX and X so that they can bind calcium and produce a blood clot. Ifvitamin 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. 17. 8. What is the mechanism of aspirin?1639. What is the mechanism of PY12 inhibitors?16410.What is the mechanism of GpIIb/IIIa receptor inhibitors?16511.What are fibrinolytic/thrombolytic drugs and how do they work?16612.What might an elevated ST segment on an ECG indicate?16713.Within what length of time would you need to implant a PCI/stent in a patient’scoronary artery if there was a blockage that had lead to MI?168Pharmacology: Arrhythmias1. What are the main causes of atrial fibrillation?1692. What are the ranges for bradycardia (low heart rate) and tachycardia (high)1703. What is the difference between a supra-ventricular (SVT) and a ventriculararrhythmia (VT)?1714. Give 2 examples of SVT andVT and how they might be identified on an ECG?1725. What is a latent or ectopic pacemaker?173163 Aspirin irreversibly inhibits cyclo-oxygenase so blocks synthesis of TXA2 and PGI2164 Block ADP binding to platelet receptors, so stop activation of platelets by ADP released from densegranules165 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 whichdegrades fibrin clots.167 ST segment is between depolarisation and repolarisation so length of AP, can indicate myocardialischaemia 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 thyroid170 Low = below 60bpm, High = above 100 bpm171 Supraventricular = origin in or above AV node. Ventricular = origin in ventricle, purkinje fibres or bundle ofHis.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 potentialand sets the heart rate.
  18. 18. 6. What produces an ectopic beat?1747. What is triggered automaticity?1758. What is re-entry and where is it likely to occur?1769. What is Wolff Parkinson White syndrome?17710.What are the 4 classes of anti-arrhythmic drugs?17811.What are the mechanisms by which adenosine and digoxin take effect on theheart?17912.How do Na+ channel blockers such as the local anesthetic lidnocane reduce theheart rate?18013.What causes the tendency of some parts of the heart to become pacemakers inthe case of ischaemia?18114.What is a radiofrequency ablation?182Physiopathology of Heart Failure174 Where localised low plasma K+ causes decreased diastolic potential (does not effectively repolarise), sothe threshold potential for Ca2+ channels is reached sooner and causes production of ectopic beat. Oftentriggered by ischaemia.175 Excessive increases in Ca2+, often drug induced, trigger premature APs176 Where an impulse becomes ʻtrappedʼ in a loop around one region of the heart. Stimulates the tissueadjacent 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 allowsAPs from the atria to the ventricles, causes a competing potential and arrhythmia. It is detected in thepresence 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 = APProlonging drugs (amiodarone), Class 4 = Ca2+ channel (verapamil)179 Both slow AVN conduction whilst digoxin increases vagal activity so slows AV node conduction. They canalso 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 APfiring.181 Ischaemia causes increased noradrenaline release which increases Ca2+ in cardiac cells, the heart hasmore of a tendency to depolarise under these conditions and one part may end up depolarising faster thanthe SAN. Noradrenaline and catecholamine also speeds up AVN conduction.182 Medical procedure where re-entrant tissue pathway is destroyed to limit
  19. 19. 1. What is the definition of heart failure?1832. What is decompensation?1843. Define ‘after-load’ and ‘preload’?1854. What does angiotensin do to the preload?1865. What is often the cause of right heart failure?1876. What does an S3 S4 gallop indicate?1887. What is ‘pitting’?1898. What is ascites?1909. Explain the difference between hypertrophy and hyperplasia?19110.Why would the right ventricle take on a larger volume for a given EDP than theleft ventricle at the same EDP?19211.Why might a distended right heart not indicate right heart failure?193183 Inability to provide adequate cardiac output to support the needs of the tissues184 When eventually, in spite or because of compensatory mechanisms, heart failure is such thatCO 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 theleft 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 preload187 Can occur in chronic pulmonary conditions where the right heart is having to work harder to pump bloodto the lungs, right heart ultimately fails due to pressure overload. OR in congestive heart failure the rightheart 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 tofill 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 sand190 edema in the peritoneal area, looks like a bloated belly191 Hypertrophy is the increase in the size of cells to make the heart dilated/distended. You only have acertain number of cardiac cells and cannot create more of them. Hyperplasia is an increase in the number ofcells of an organ.192 Because the right heart has a thinner wall193 Could have been distended compensating for a failing left heart without failing itself
  20. 20. 12.What are typical hydrostatic pressures for the pulmonary vein and pulmonaryartery?19413.What causes muscle weakness and generalized weakness in heart failure?19514.Why do mechanisms for increasing cardiac output during exercise not functionproperly in a failing heart?19615.How would increased muscle mass (cardiac hypertrophy) appear on an ECG?19716.What is the difference between a dilated heart and cardiac hypertrophy?198Treatment of Heart Failure1. What are the possible adverse effects of using ACE 1 inhibitors?1992. Why would you use Angiotensin II receptor blockers instead of Angiotensin Ireceptor blockers?2003. What positive effect might using diuretics have on the respiratory system?2014. What are the negative side effects on cardiac function can be caused by thiazideand loop diuretics?2025. What could you do to reduce this effect?203194 Vein 10mmHg, Artery 20mmHg195 Not enough blood perfusing tissues because of failing heart but also because the compensatorymechanisms making up for failing heart constrict the arteries to skeletal muscle in an attempt to divert bloodflow to the heart.196 Because the heart is already compensating in this way, it is working at maximum output or evendecompensating. It also becomes less sensitive to noradrenaline.197 Rightward shift of cardiac index198 In both cases the heart will appear ʻbiggerʼ but in hypertrophy this is because the cells are bigger andthere 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 theafferent 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 itis less active when Angiotensin 1 blockers are used. Angiotensin 2 blockers have no effect on bradykininlevels.201 Increase exercise capability by reducing dyspnoea (breathlessness/pulmonary edema)202 Excessive K+ loss leading to slower repolarisation and resulting arrhythmias203 Give a K+ sparing diuretic in addition, spironolactone (aldosterone antagonist) or K+ supplements
  21. 21. 6. What are the negative side effects of spironolactone?2047. What is ivabradine?2058. What are the main positive effects of B-blockers?2069. What kind of drugs reduce afterload?20710.What are cardiac glycosides and what is their mechanism?20811.Why do cardiac glycosides not prolong survival in heart failure (apart fromcausing arrhythmias?20912.Why might cardiac glycosides cause arrhythmias?21013.How do B1 agonists work?21114.What diagnosis would you make of an ejection fraction of (i) less than 45% (ii)more than 50% (iii) less than 40%21215.How do PDE inhibitors work?213Atherosclerosis1. Name the 4 basic structural layers of a muscular artery?214204 Gynecomastia, hyperkalaemia (because aldosterone normally causes K+ secretion) and renaldysfunction205 An inhibitor of ‘If’ so slows heart rate and stabilises heart, reducing the chance of arrythmias206 Negative inotropes which reduce cardiac remodelling and rennin release, decrease symptoms of heartfailure207 Vasorelaxants such as hydralazine and isosorbide dinitrate208 Increase contractility by inhibiting K+(in)/Na+(out) pumps in cardiac muscle cells. More Na+ in cellreduces 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 treatatrial fibrillation because they reduce AVN conduction.210 Because they increase the excitability of the tissue and may lead to a delayed after polarisation211 Opposite of beta blockers, they act like noradrenaline and stimulate release of adenylate cyclase whichstimulates cAMP release which increases force and heart rate212 Less than 45= moderate systolic dysfunction, greater than 50=diastolic dysfunction, less than 40 = severesystolic dyfunction213 PDE III mediates the conversion of cAMP into 5-AMP (inactive form) so means cAMP retains its activeform for longer214 Endothelium, tunica intima, tunica media, tunica adventitia
  22. 22. 2. Which parts of the artery structure does atherosclerosis affect?2153. What is Monchebergʼs Medial Sclerosis?2164. Describe the stages of formation of a fatty atheromatous plaque (not embolism)2175. What are vasa vasora?2186. What is intermittent claudication?2197. What is the most common location for aneurysm?220215 Intima and internal elastic lamina216 Calcification of muscular arteries217 Lipid crosses endothelium in high levels from blood, phagocytosed by macrophages (monocytes), highlevel of lipid present in macrophages in the intima, smooth muscle cells migrate from media to intima, theseare modified under these condition so that they are also able to phagocytose lipid and start producing lipidrich collagen, collagen plaques then appear white, fatty plaque obscures media (SM) and therefore arteryweaker, less able to constrict but gets blocked by lipid. May lead to aneurysm (abnormal dilatation andbursting) 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

×