Retired__LSS1__Cardiovascular Flashcards
1
Q
State the three layers of the heart from inside to out, and their function
A
Endocardium: one cell thick layer of tissue attached to the basement membrane of the myocardium, interfacing the blood and myocardium
Myocardium: thick layer of cardiac muscle cells
Pericardium: layers of fibrous tissue that hold the heart in place (fixes to mediastinum) and protect from damage (and infection)
2
Q
State the layers of the pericardium from inside to out, and their functions
A
Epicardium / Visceral pericardium: layer of serous tissue attached to the myocardium, separating muscle from the pericardial fluid
Pericardial fluid: protects the heart from external forces and shock
Parietal pericardium: layer of serous tissue lining the fibrous pericardium and facing the pericardial space
Fibrous pericardium: connective layered tissue to protect heart and anchor to mediastinum as well as preventing overfilling
3
Q
State the structure of the four heart valves and the mechanical attachment to the heart
A
Structure: all tricuspid except LA > LV mitral valve which is bicuspid (one larger than other)
Attachment: chordae tendineae attach to papillary muscles
4
Q
Summarise the anatomy of the coronary circulation
A
Coronary arteries: there are THREE, which branch off to superior vessels; all originate superior to the aortic valve, coming from the right and left cusp
Left cusp: artery bifurcates to the left circumflex and left anterior descending summarise the anatomy of the coronary circulation
Right cusp: right coronary artery
Coronary veins: collect blood and feed to coronary sinus at the back of the heart which drains into the right atrium
5
Q
Explain the sequence of events leading to contraction and relaxation of cardiac muscle
A
1) AP opens L-type Ca2+ channels, leading to influx2) Influx causes calcium induced calcium release by inducing conformational change in RyR that allows for an efflux from the sarcoplasmic reticulum3) Calcium binds to troponin to move tropomyosin4) Ca2+-ATPase uses ATP to pump calcium against the concentration gradient back to the SR - so all released by the SR is reabsorbed
5) Na+/Ca2+ exchanger uses downhill gradient of Na+ to efflux calcium from cell - so all that entered via the L-type Ca2+ channels exits
6
Q
Define preload, afterload, isometric contraction and isotonic contraction
A
Preload: weight stretching a muscle before stimulated to contract
Afterload: weight not apparent to muscle in a resting state, only encountered after starting to contract
Isometric contraction:no change in fibre length but pressure increases
Isotonic contraction:shortening of fibres
7
Q
Explain the isometric-preload and isotonic-afterload relationship
A
A greater pre-load leads to greater force in the contraction because stretching leads to increased force; a greater after-load leads to a reduced shortening and velocity in the isotonic contraction because the same force is exerted but a larger force must be overcome
8
Q
Describe the in-vivo correlates of preload and afterload in the heart, and the measurement that represents each
A
Preload: wall stress at end of diastole, as caused by blood filling and stretching ventricular walls; measured by end-diastolic pressure
Afterload: wall stress during systole, caused by the blood pressure of blood in the arteries against which blood must be pumped out; measured by diastolic blood pressure
9
Q
Draw and label a Pressure-Volume Loop
A
“A = mitral valve closes, B = aortic valve opens, C = aortic valve closes, D = mitral valve opens”
10
Q
Explain the effect of modifying the preload on a pressure-volume loop
A
“Increase: more filling leads to a larger volume of blood, so fibres contract more strongly to produce a larger stroke volume BUT no change in final pressure
Decrease: reduced filling leads to lower volume of blood, so fibres contract more weakly to produce a smaller stroke volume with NO change in final pressure
”
11
Q
Explain the effect of modifying the afterload on a pressure-volume loop
A
“Increased afterload leads to a smaller stroke volume because ventricle walls do not shorten as much, reducing the force and velocity at which blood is ejected, so the start-diastolic volume is larger because less blood can be ejected
”
12
Q
Explain the mechanisms of Starling’s Law of the Heart
A
Starling’s Law: increased filling (preload) leads to increased force of contraction and hence greater stroke volume so that cardiac output exactly balances venous returnMechanisms:- Increased stretching reduces the actin-myosin overlap, so more crossbridges can be made- Troponin C has a higher affinity for calcium when stretched, so it binds more readily
13
Q
State the Law of Laplace and the equations for wall tension
A
Law of LaPlace: when pressure in cylinder is constant, tension on walls increases with radius
Wall tension = vessel pressure x vessel radius
With thickness: T = (PxR)/h
14
Q
Explain the relationships between Law of LaPlace and mechanics
A
- In order to achieve equal wall tension in each ventricle, pressure in right ventricle must be reduced because it has a larger radius- As left ventricle has a lower radius, it can generate a greater pressure for the same wall tension- Heart failure leads to dilation, producing a larger radius and hence greater wall stress
15
Q
Define contractility and state how it is measured and affected
A
Contractility: force of myocardial contraction
Measured by: ejection fraction
Increased by: sympathetic stimulation
16
Q
Briefly outline each stage of the cardiac cycle, including their [ECG Reading] and {Heart Sounds}
A
1) Atrial Systole: atria top up ventricles [P wave] {S4 - Abnormal}2) Isovolumetric Contraction: ventricular pressure increases for no fibre shortening [QRS] {S1}3) Rapid Ejection: SL open when outward pressure gradient and fibres shorten as blood ejected [ST]4) Reduced Ejection: SL begin to close as ventricles repolarising and pressure gradient decreased [T Wave]5) Isovolumetric Relaxation: ventricle volume constant as pressure decreases [isoelectric] {S2}6) Rapid Passive Filling: AV valve opens to allow atrial blood to passively move into ventricles down pressure gradient [isoelectric] {S3 - Abnormal}7) Reduced Passive Filling: pressure gradient reduced so flows more slowly - LONGEST PHASE
17
Q
Define end-diastolic, end-systolic and stroke volume, giving normal results
A
EDV: volume of blood in ventricle just before contraction (normal = 110ml)
ESV: volume of blood in ventricle just after contraction (normal = 40ml)
Stroke Volume: EDV - ESV (normal = 70ml) = blood pumped per heart beat
18
Q
Define normal systolic, diastolic, pulse, mean arterial and atrial pressures
A
Systolic: 120mmHg Diastolic: 80mmHg Pulse: 40mmHg MAP: 93mmHg Atrial: <30mmHg
19
Q
Define laminar and turbulent flow, linking this to a parabolic velocity profile
A
“Laminar flow: flow in layers, where those closest to centre of lumen flow fastest as less resistance
Turbulent flow: flow erratic, forming eddys and prone to pooling (pathological changes to endothelium)
Parabolic velocity profile: the further from the wall, the faster the velocity of the blood, and when plotted parabolically, the tangent at any point is the shear rateShear rate x viscosity = shear stress
”
20
Q
Explain laminar and turbulent shear stress and how this links to blood pressure measurement
A
Laminar Shear Stress: high level of shear stress produced by laminar flow causes endothelial cells to grow in one direction and produce secretions for anticoagulation and vasodilation
Turbulent Shear Stress: low level of shear stress produced by turbulent flow leads to endothelial proliferation and shape change, producing secretions for coagulation and vasoconstriction
BP Measurement: release of cuff leads to audible turbulent flow
21
Q
Recall Poiseuille’s Equation and it’s physiological application
A
Equation: Resistance = (8 x length x viscosity)/(pi x radius4)
Application: length and viscosity do not change rapidly, but radius can in vasoconstriction/dilation; halving the radius leads to a 16-fold decrease in flow
22
Q
Explain the concept of vascular compliance, and the link to elastance
A
Compliance: ability of a vessel to distend and increase its volume with increasing transmural pressure
Elastance: inverse of compliance, produced by presence of elastin fibres in the vessel wall, giving ability to recoil and maintain pressure
Equation: compliance = change in volume/change in pressure
Arteries: low compliance, high elastance, recoiling to maintain pressure
Veins: high compliance, low elastance, distending to store blood
23
Q
Explain the Windkessel effect and how compliance can be internally and externally controlled
A
Windkessel effect: recoil of the arteries ensures continual flow despire pulsatile flow from heart
Internal: RAAS and endogenous vasodilators/constrictors
External: stockings apply pressure to veins to prevent large increase in volume
24
Q
Explain the effect of gravity on flow and the response to standing
A
Gravity: pulls blood toward ground so promotes pooling
Standing: increases hydrostatic pressure, so blood transiently pools in veins; will collapse if not compensated
25
Recall the Law of Laplace (vascular), including the wall stress, and explain the relationship to blood flow
Law of Laplace: tension = pressure x radius
Wall stress = (pressure x radius)/thickness
Relationship to flow: increasing radius increases flow but requires a thicker wall to deal with increased tension
26
Define cardiac output, stroke volume and mean systemic arterial pressure and state their determinants
Cardiac Output: SV x HR; volume pumped by heart min-1 (approx 5litres)
Strove Volume: EDV - ESV; volume pumped per beat (approx 70ml)
Pulse Pressure: SBP - DBP (approx 40mmHg)
Mean Arterial Pressure: DBP + 1/3 pulse pressure (approx 93mmHg)
27
Explain the potassium hypothesis and how the resting membrane potential may be calculated
Potassium hypothesis: potassium ions can move over cell membrane while Cl- cannot, so diffuse out of cell down concentration gradient until equilibrium with opposite electrostartic repulsive force reached
Calculation: goldman-hodgkin-satz equation, taking into account K+, Na+ and Cl- to calculate membrane potentials
28
Draw a cardiac action potential and explain each stage
"0) UPSTROKE - Sodium permeability increases to allow an Na+ influx1) EARLY REPOL - Transient outward current due to brief K+ efflux 2) PLATEAU - Calcium permeability increases to allow a Ca2+ influx and CICR to prolong the AP3) REPOL - Potassium permeability increases slowly to partially repolarise, and when becomes low enough, IK1 channels open to efflux a large amount of K+ and return to RMP4) RMP - Some IK1 remain open to stabilise "
29
Draw action potentials for the ventricle and sino-atrial node, explaining the difference
"Differences:- SA Node always oscillates- SA Node has no IK1 and hence no RMP- SA Node sodium channels open to produce a little depolarisation in diastole, but the upstroke is provided by a calcium influx"
30
Explain the location and role of the SAN
Location: below epicardial surface at RA/SVC boundary
Role: spontaneously depolarise to allow autorhythmic contraction (start conduction pathway)
31
Explain how intrinsic heart rate can be modulated, describing the effects of the PNS and SNS
PNS: vagus nerve from VMC uses ACh to increase the length of an SA node AP, so the SAN depolarises more slowly
SNS: increases contractility (inotropy) and heart rate (chronotropy) using noradrenaline to decrease the length of an SA node AP, so the SAN depolarises more quickly
32
Describe both cardiac refractory periods and their importance
Absolute: NO action potentials can be initiated regardless of intensity due to Na+ channel inactivation
Relative: larger than normal stimulus can produce an AP as hyperpolarised
Importance: prevent tetanic contraction to allow the heart to fill
33
Explain cardiac conduction pathways and how impulses can spread
1) SAN spontaneosly depolarises to send a wave of depolarisation throughout atria2) Internodal fibres carry wave throghout atrial myocardium3) AVN delays wave to allow ventricular filling and contraction separation4) Bundle of His rapidly conducts impulse to apex5) Ventricular fibres allow upward spread of impulse from apex to cause ventricular contraction
Propagation: gap junctions with connexons allow waves of depolarisation to spread cell to cell
34
Define autoregulation of arteries and the two theories to explain it
Autoregulation: intrinsic capacity to compensate for reduced perfusion pressure by decreasing resistance to increase flow
Myogenic theory: smooth muscle fibres in wall respond to tension, so reduced perfusion causes relaxation to increase radius and hence flow
Metabolic theory: decreased flow leads to accumulating metabolites, causing dilation to increase flow and wash these away
35
State the hormones involved in local and systemic control of flow
Vasodilators:
- Local: NO and prostacyclin
- Systemic: Kinins and ANPVasoconstrictors:
- Local: Thromboxane A2 and endothelins
- Systemic: ADH, AGTII and (nor)adrenaline
36
Describe the pattern of vascular SNS innervation and the location/structure of the vasomotor centre
SNS Innervation: heart and all vessels except capillaries (as well as kidneys, gut and spleen)
VMC Location: located bilaterally in the medulla and lower third of the pons
VMC Structure: vasoconstricor, vasodilator and cardioregulatory inhibitory area; lateral portions control HR and contractility; medial portions control vagus nerve to change HR
37
Describe the binding, MoA and normal activity of noradrenaline in SNS CVS activity
Vessels: binds to alpha1 receptors causing vasoconstriction (decreasing flow)
Heart: binds to beta1 receptors to increase force of contraction (hence SV too)
MoA: binding increases cAMP, activating PKA to phosphorylate and activae L-type Ca2+/SR release channels to cause calcium influxes
Tonic activity: always baseline level of firing so can be decreased for vasodilatioon or increased for constriction by depressor/pressor VMC regions
38
State the function, location and innervation of baroreceptors
Baroreceptors: specialised cells that can detect blood pressure, whose firing mirrors that of blood pressure
Carotid sinus baroreceptors: send impulses down glossopharyngeal PNS afferent to VMC
Aortic arch baroreceptors: send impulses down vagus nerve PNS afferent to VMC
39
Describe the actions of increased firing of baroreceptors
- Increases PNS efferent firing down vagus nerve to decrease HR- Increase inhibitory interneuron firing, inhibiting SNS tonic activity, causing vasodilation and slowing HR
40
Explain the vascular response to haemorrhage by baroreceptors
Haemorrhage: \/ SV = \/ Baroreceptor firing = ...- Reduced PNS/Increase SNS firing to increase contractility and SV- Increased SNS discharge to veins to increase tone- Increased SNS discharge to arterioles to cause vasoconstriction- MAP = QxTPR, increased by higher SV and vasoconstriction
41
Explain the supply of blood to, and removal from, the microcirculation
1st order arterioles are lined by smooth muscle and branch to capillaries via terminal arterioles, with precapillary sphincters to control flow to capillary beds; venules collect blood to return to veins/heart
42
Define organ flow and what blood flow depends on
Organ flow = pressure change / resistance of organ
A = MAP (avg 93mmHg), B = venous pressure (avg 37mmHg)
Flow: depends completely on resistance
43
Explain the need for arteriolar radii adjustment, and define active hyperaemia and myogenic autoregulation
Radii adjustment: allows for matching of blood flow to metabolic need and regulation of systemic arterial blood pressure
Active hyperaemia: increased [metabolites] and oxygen usage by active tissue leads to arteriolar vasodilation to increase flow
Myogenic autoregulation: decreased blood temperature or increased distention leads to arteriolar vasoconstriction to decrease flow to capillaries
44
Describe the three difference wall structures possible in capillaries and the role of sphincters
Continuous capillaries: junctions between endothelial cells are filled with water - water soluble and small molecules diffuse over gap junctions, large and water soluble molecules require transport proteins, small and lipid soluble molecules can diffuse straight across
Fenestrated capillaries: many small gaps (fenestrations) - making walls leaky e.g. Glomerulus
Discontinuous capillaries: large gaps between cells e.g. Bone marrow / liver
Sphincters: allow almost complete occlusion to reduce muscle blood flow at rest
45
Explain the structure and function of the lymphatic system
Lymphatic system: lymphatic capillaries (blind-ended - not a loop) lie alongside blood capillaries (closed loop) - returns xs fluid to blood and performs immune surveillance
Immune defence: lymph nodes present throughout system; any infection in fluid exposes B/T-Cells to the antigens
Flow: no pump, draining to right lymphatic and thoracic ducts into the right and left subclavian veins (3L/day)
46
Describe how prostaglandins are synthesised, including the specific pathways to produce TXA2 and PGI2
1) Phospholipase A2 catalyses the conversion of membrane phospholipids to arachidonic acid2) COX1 and COX2 convert arachidonic acid to PGH2 (prostaglandin H2)
Thromboxane Synthase: converts PGH2 to thromboxane A2 (pro-platelet vasoconstrictor)
Prostacyclin Synthase: converts PGH2 to prostacyclin (anti-platelet vasodilator)
47
State the vasodilator molecules produced in the endothelium and the key features of their mechanisms
Molecules: Nitric Oxide and ProstacyclinKey Features: - use -yl cyclase second messengers in the VSMC- use XTP/cXMP in VSMC to cause relaxation- anti-platelet
48
State the vasoconstrictor molecules produced in the endothelium and the key features of their mechanisms
Molecules: Thromboxane A2, Angiotensin II, and Endothelin I Key Features: - use phospholipase C second messengers in the VSMC- use PIP2/IP3 in VSMC to cause contraction
49
Explain how nitric oxide is synthesised and its mechanism of action
Synthesis:1) ACh binds to endothelial GPCR, activating PLC to migrate along membrane and convert PIP2 to IP3 and DAG2) IP3 leads to ER Ca2+ release, upregulating endothelial nitric oxide synthase3) eNOS converts L-arginine + O2 to L-citrulline and NOMoA:1) NO diffuses to VSMCs and activates guanylate cyclase, converting GTP to cGMP2) cGMP upregulates protein kinase G3) PKG activates K+ channels, hyperpolarising the cell to cause relaxation
50
Explain how prostacyclin is synthesised and its mechanism of action
Synthesis:1) Arachidonic acid produced from phospholipids (phospholipase A2) or diacyl glycerol (DAG lipase)2) Arachidonic acid converted to PGH2 using COX1/23) PGH2 converted to PGI2
MoA:1) PGI2 diffuses to VSMCs and binds to membrane IP receptors to activate adenylate cyclase, converting ATP to cAMP2) cAMP inhibits myosin light chain kinases causing cell relaxation
51
Explain how thromboxane A2 is synthesised and its mechanism of action on VSMCs and platelets
Synthesis:1) Arachidonic acid produced from phospholipids (phospholipase A2) or diacyl glycerol (DAG lipase)2) Arachidonic acid converted to PGH2 using COX1/23) PGH2 converted to TXA2
MoA VSMC:1) TXA2 binds to TPbeta receptors on VSMCs, activating PLC to migrate and convert PIP2 to IP3 and DAG2) IP3 triggers Ca2+ influx from ER to upregulate MLCK, causing contraction and vasoconstrictionMoA Platelet:1) TXA2 binds to TPalpha receptors on platelets, activating them to produce more TXA2 in a positive feedback response2) Platelets aggregate for haemostasis
52
Explain how Endothelin I is synthesised and its mechanism of action on endothelial cells and VSMCs
Synthesis:1) Endothelial cell nucleus produces Big Endothelin I2) Endothelin converting enzyme converts to ET IMoA VSMC:1) ET I binds to ETA and ETB receptors on VSMCs, activating PLC to migrate and convert PIP2 to IP3 and DAG2) IP3 triggers Ca2+ influx from ER to upregulate MLCK, causing contraction and vasoconstrictionMoA Endothelial Cell:1) ET I binds to endothelial ETB receptors to upregulate eNOS
2) eNOS increases NO production which diffuses to VSMCs to cause relaxation and vasodilation
53
Compare the actions of Endothelin I, and how they may be increased/decreased
Actions: simultaneous vasoconstriction +++ and vasodilation +
Increased: using agonists - adrenaline, AGTII, ADH
Decreased: using antagonists - NO, heparin, prostacyclin
54
Describe how Angiotensin II is synthesised, and the role of ACE
1) Angiotensinogen produced by the liver and released to the bloodstream 2) Kidney juxtaglomerular cells release renin in response to decreased blood pressure, sympathetic stimulation or decreased sodium reaching the macula densa cells 3) Renin catalyses the production of angiotensin I from angiotensinogen 4) ACE in the lung/kidney vessel endothelial cells converts angiotensin I to angiotensin II and metabolises bradykinin to reduce nitric oxide synthesis
55
State the mechanisms of action of Angiotensin II, describing the vasoconstriction mechanism
- Increased ADH secretion (more vasoconstriction and water retention)- Increased aldosterone secretion (more sodium absorbed so more water retention)- Increased kidney sodium reabsorption- Upregulated sympathetic system excitation to cause vasoconstriction and increased HR- Arteriolar vasoconstriction
MoA VSMC:
1) AGT II binds to AT1 receptors on VSMCs, activating PLC to migrate and convert PIP2 to IP3 and DAG
2) IP3 triggers Ca2+ influx from ER to upregulate MLCK, causing contraction and vasoconstriction
56
Describe the pattern of expression of COX1 and COX2, and the mechanism of action of aspirin
COX-1 constitutively expressed in all cells; acetylation by aspirin inactivates
COX-2 upregulated in physiological insult; acetylation switches function to generate protective lipids
MoA: irreversible inhibition of COX enzymes, preventing the conversion of arachidonic acid to PGH2 to prevent thromboxane A2 formation
57
Explain the MoAs of nitrovasodilators, calcium channel blockers and ACE inhibitors
Nitrovasodilators: found in GTN sprays, including NO functional group, donating ready to use NO - short acting and drops BP in short term
Calcium Channel Blockers: effective antihypertensives that prevent IP3 causing a Ca2+ influx to VSMCs, preventing contraction and vasoconstriction
ACE Inhibitors: prevent AGT I being converted to AGT II to prevent downstream vasoconstriction
58
Describe the structure of blood vessels from lumen to exterior
- Lumen: hollow area through which blood may flow - Tunica Intima / Endothelium: one cell thick and allows for exchange and homeostasis/haemostasis - Internal Elastic Tissue
- Tunica Media / Smooth Muscle: unconsciously controlled smooth muscle cells - External Elastic Tissue
- Tunica Adventitia / Fibrous Connective Tissue: protects the vessel and contains the nerves and blood supply (vasa vasorum) to the vessel
59
Contrast the resting and activated endothelium
Resting Endothelium: is inactivated and anti inflammatory/thrombotic/proliferative
Activated Endothelium: is pro inflammatory/thrombotic/angiogenic
60
List some endothelium activating factors and processes that occur after activation
Activating Factors: viruses, smoking, thrombosis, mechanical stress, hypertension, hyperglycaemia, inflammation - chronic activation leads to pro-inflammatory/thrombotic effects
Activated Endothelium Processes: thrombosis, senescence, increased permeability and leukocyte recruitment
61
Describe what is meant be endothelial cell senscence, comparing the benefit and risk
Senescence: damaged/ageing cells undergo growth arrest to halt proliferation in response to stress/damage; stops damaged cells replicating but cells become pro-inflammatory and contribute to CVD
62
State the effect of increased endothelial permeability following activation
Permeability usually regulated by endothelium, and increased permeability allows plasma protein leakage, and for lipoproteins to pass over and bind to proteoglycans; here they are oxidised before macrophages engulf them to form foam cells
63
Describe the normal interaction of leukocytes with large arteries, in smaller vessels and following activation
Large Arteries: usually leukocytes bind weakly with selectin and roll
Inflammation: bind strongly with selectin to post-capillary venule endothelial cells and transmigrate to tissues
Activated Arteries: bind strongly with selectin and transmigrate to become stuck in sub-endothelial spaces
64
Describe the pathophysiology of atherosclerosis
1) Activation of the endothelium causes leukocytes to strongly adhere and migrate into the sub-endothelial space (endothelial dysfunction) 2) The activated endothelium becomes more permeable and so lipoproteins diffuse into the sub-endothelial space, bind to proteoglycans and are oxidised; macrophages engulf these to become foam cells (fatty streak formation) 3) Macrophages accumulated and die to form a necrotic core alongside angiogenesis and senescence (advanced complicated lesion forms)
65
State the transcription factors and epigenetic changes associated with laminar and turbulent flow
Laminar: KLF2/4 upregulate eNOS; DNA methyltransferases downregulated to demethylate and activate anti-atherotic gene promotor regions
Turbulent: NK-kappaB causes inflammation; DNA methyltransferases upregulated to methylate and repress anti-atherotic gene promotor regions
66
Explain where athersclerosis occurs most frequently and why
Tends to occur at branch points where turbulent flow occurs and the blood continuously changes speed and direction
67
What does an upward/downward deflection on an ECG represent, and the width/gradient of such a deflection
Upwards: depol to cathode (+) or repol to anode (-)
Downwards: depol to anode (-) or repol to cathode (+)
Width: duration
Gradient: velocity
68
Describe the P, PR, Q, R, S, ST, T and U regions of an ECG
P Wave: SAN = atrial depolarisation towards cathode
PR Segment: AVN depolarises to pause impulse - isoelectric
Q Wave: septum depolarises away from cathode
R Wave: ventricular depolarisation using Purkinje fibres - impulse towards cathode
S Wave: P. Fibres carry wave up myocardium for late depolarisation - impulse away from cathode
ST Segment: depolarised ventricles = isoelectric
T Wave: ventricular repolarisation moves away from cathode
U Wave: P. Fibre repolarisation
69
Describe where the 10 electrodes are placed on the body for a 12-lead ECG
Limb leads: Ride Your Green Bike (going clockwise from right shoulder)
- Red: Right Arm - Yellow: Left Arm - Green: Left Leg - Black: Right Leg Chest leads: - V1: 4th intercostal, right sternal margin - V2: 4th intercostal, left sternal margin - V3: in-between V2 and V4 (on top of 5th rib) - V4: 5th intercostal, mid-clavicular line - V5: 5th intercostal, anterior axillary line (usually half-way between V4/V6) - V6: 5th intercostal, mid-axillary line
70
Describe how Einthoven's triangle is constructed, including the bipolar leads and net deflections
Bipolar leads: measure potential difference between the limbs with physical anodes and cathodes
Net deflections: for a given complex is the sum of the net deflections of the other two leads
Lead I: Right Arm to Left Arm
Lead II: Right Arm to Left Leg
Lead III: Left Arm to Left Leg
71
Describe what the unipolar and precordial ECG leads represent
Unipolar leads: measure the potential difference between a null point with relative 0 potential at the centre of the triangle (anode) and a physical cathode
aVL: LA cathode
aVR: RA cathode
aVF: LL cathode
Precoridal leads: use the chest electrodes as cathodes, measuing electrical activity flowing from heart
72
State the leads that give lateral, inferior, septal and anterior views of the heart and the corresponding arteries
Lateral: I, aVL, V5, V6 - Left Circumflex
Inferior: II, III, aVF - Right Coronary
Septal: V1, V2 - Left Anterior Descending
Anterior: V3, V4 - Right Coronary
73
State the angles of leads I, II, III, aVL, aVF and aVR and hence the three pairs that can be used to work out the cardiac axis
I: 0o
II: 60o
III: 120o
aVL: -30o
aVF: 90o
aVR: -150o
Axis Pairs: I + aVF; II + aVL; III + aVR
74
Explain how to calculate a cardiac axis
"1) Select any pair of perpendicular leads e.g. I/aVF or II/aVL2) Work out the net deflection of the QRS complex on each lead3) Plot the deflections as a triangle on a clockface4) Use inverse tan to calculate theta5) Adjust the angle to account for the axes selected if necessary
"
75
Explain the appearance of an ECG showing Sinus Bradycardia
P:QRS 1:1Regular rate <60bpm
76
Explain the appearance of an ECG showing Sinus Tachycardia
P:QRS 1:1Rate regular >100bpm
77
Explain the appearance of an ECG showing Sinus Arrhythmia
P:QRS 1:1Irregular rate approx 60-100bpm
78
Explain the appearance of an ECG showing Atrial Fibrillation
"Oscillating baseline with asynchronous atrial contractionIrregular and slow rhythm
"
79
Explain the appearance of an ECG showing Atrial Flutter
"Regular saw tooth pattern Atrial:ventricular beats 2:1/3:1Not visible in all leads
"
80
Explain the appearance of an ECG showing 1st Deg HB
"P:QRS 1:1PR Interval extended due to slower AV conductionMostly benign
"
81
Explain the appearance of an ECG showing 2nd Deg HB Mob1
"Increasing PR until missed QRSRegularly irrefular due to diseased AV
"
82
Explain the appearance of an ECG showing 2nd Deg HB Mob2
"No PR elongation, with regular P-P and R-RQRSs skipped in regular pattern e.g. 2:1Can rapidly deteriorate
"
83
Explain the appearance of an ECG showing 3rd Deg HB
"Regular P and QRS but no relationship - true non-sinus rhythm AVN/myocardium are auto-rhythmic P wave rate > QRS rate
"
84
Explain the appearance of an ECG showing VTach
"P waves hidden in dissociated atrial rhythm Ventricles beating regularly, rapidly and very hardGrim reaper rhythm - shockable and can deteriorate to VFib
"
85
Explain the appearance of an ECG showing VFib
"HR > 250bpmShockable and no outputHoly shit rhythm
"
86
Explain the appearance of an ECG showing ST Elevation
"ST-Segment elevated >2mm above isoelectric lineCaused by infarction
"
87
Explain the appearance of an ECG showing ST Depression
"ST-Segment depressed >2mm below isoelectric lineCaused by ischaemia
"
88
Define hypertension, state its epidemiology and the affect of aging
Hypertension (HTN): BP above which investigation and treatment to more good than harm
Epidemiology: affects 1bn worldwide and is the leading cause of death
Aging: mean SBP and PP rise with age (DBP does not) - so by 80 almost all are 'hypertensive'
89
Describe the aetiology and genetic component of hypertension
Aetiology: rarely monogenic, usually polygenic and influenced by environment (salt intake, obesity, exercise, alcohol, pregnancy etc.)
Genetics: 30-50% variation attributable to genetics
90
Diferentiate between primary and secondary hypertension, listing possible causes
Primary Hypertension: 85-95% cases - idiopathic
Secondary Hypertension: 5-15% cases - known cause
Possible 2o HTN causes: renal disease, aldosterone/catecholamine tumours, pre-eclampsia, oral contraceptives, etc.
91
Describe the features associated with established hypertension
- Increased TPR- Decreased arterial compliance- Normal CO- Normal blood volume- Central shift in volume 2/2 reduced venous compliance
92
Describe cardiovascular consequences of hypertension (5)
Heart: cardiomegaly due to increased LV wall mass
CHF: hypertension increases risk 2-3 fold
Large arteries: artery wall thickness increases to withstand extra wall stress
Aneurysms: dilation of medium-large arteries can lead to thrombosis/haemorrhage on rupture
CVAs: mostly due to clotting and thrombosis
93
Describe non-cardiac consequences of hypertension (4)
Eyes: microvascular damage to retina leads to swelling, reduced perfusion and ocular damage
Microcirculation: hypertension reduces capillary density and leads to damage/leakage - resistance increases and wall thickens
Kidneys: renal dysfunction/failure
Microalbuminuria: HTN increases albumin loss to urine as reduced glomerular filtration rate
94
State possible pharmacological treatments of hypertension
ACE Inhibitors: reduce AGTII production using RAAS
Angiotensin receptor blockers: reduce AGTII binding
Loop Diuretics: block water reabsorption in crisis
Thiazide Diuretics: slowly reduce PVR
Beta Blockers: beta1 receptors on heart blocked to reduce HR/contractility (also reduces renin secretion in kidneys)
Calcium Channel Blockers: stop cross bridge cycling in VSMCs to reduce vasoconstriction
95
Describe the structure of von Willebrand Factor and how it is normally present in the body
Structure: giant adhesive proteins; usually multimers, with binding sites for collagen, platelets, and factor VIII
Normally: present in rolled up state in blood so binding sites are hidden
96
Destcribe the structure, receptors, activation and binding of platelets
Structure: enucleated megakaryocyte fragments containing alpha granules (vWF/fibrinogen) and dense granules (serotonin/ADP/Ca2+)
Receptors: surface receptors bind vWF (GP1b) and fibrinogen (GPIIb/IIIa)
Activation: change shape to expose phospholipids, present proteins and release granules
Binding: vWF via GP1b to slow down and allow secondary collagen binding; bind to each other using fibrinogen via GPIIb/IIIa
97
State the order of responses in haemostasis
1) Vasoconstriction (endothelin and neural)2) Platelet plug3) Fibrin mesh
98
Outline the process of primary haemostasis
1) Endothelium damaged, exposing collagen2) Rolled up vWF binds to collagen, stretching out due to blood shear stress, exposing platelet binding sites3) Platelets bind to vWF using GP1b, activating them to release alpha and dense granules, to change shape and to express activated GPIIb/IIIa receptors4) vWF allows more platelets to be captured and fibrinogen allows platelets to stick together using GPIIb/IIIa
99
Outline the process of secondary haemostasis
1) Endothelium is damaged, exposing tissue factors2) Circulating FVIIa binds to tissue factors forming a complex that converts FIX to FIXa and FX to FXa3) Tissue Factor Pathway Inhibitor (TFPI) binds to FVIIa, FXa, FIXa and TFs to limit pathway4) If large enough stimulus enough FXa remains to convert FII to Thrombin (FIIa)5) Thrombin activates FVIII to allow it to form a complex with FIXa, Ca2+ and Phospholipids that converts FX to FXa6) Thrombin also activates FV to allow it to form a complex with FXa, Ca2+ and Phospholipids that converts FII to thrombin7) Thrombin burst occurs and cleaves fibrin from fibrinogen
100
Describe how anticoagulation occurs at rest and using antithrombin/heparin
Rest: collagen/TFs are separated from vWF, platelets and FVIIa; endothelial proteins are also anti-thrombotic e.g. heparin and NO
Antithrombin: binds to thrombin, neutralising it and directly inhibiting FIXa and FXa
Heparin: makes antithrombin more reactive
101
Describe the role of Protein C and thrombomodulin in anticoagulation
Thrombomodulin: catches thrombin if it tries to move, preventing clot from spreading
Protein C: endothelial thrombomodulin that has bound thrombin changes its action to activating protein C, allowing it to combine with cofactor protein S to degrade FVIIIa and FVa
102
Outline the process of fibrinolysis
1) Tissue Plasminogen Activator and Plasminogen bind to fibrin, allowing cleaving to Plasmin2) Plasmin cleaves fibrin to produce fibrin degradation products 3) Antiplasmin stops plasmin from moving to rest of circulatory system to prevent all systemic fibrin being degraded, localising response
103
"Describe what is meant by ""abnormal bleeding"" and common features of a history "
Abnormal bleeding: spontaneous bleeding that is out of proportion to the injury, that is prolonged and/or that restarts after appearing to stop Common features of bleeding disorder histories:- Epistaxis not stopped by 10 minutes compression- Bruising with no apparent trauma- Prolonged bleeding from trivial wounds- Menorrhagia leading to treatment or anaemia
104
List causes of primary haemostasis problems and the expected bleeding pattern
Causes: - Defective collagen e.g. Scurvy/steroids- von Willebrand disease - abnormal/no vWF so no plug forms- Platelet deficiency e.g. Aspirin
Bleeding Pattern: never begin coagulation so immediately bleed with easy bruising, bleeding after trauma and nosebleeds
105
List causes of secondary haemostasis problems and the expected bleeding pattern
Causes: - Haemophilia: prevents thrombin burst as no FVIII - so inadequate fibrin mesh forms and the plug will fall apart- Liver disease: clotting factors made in liver- Warfarin usage: inhibits production of clotting factorsExpected Bleeding Pattern:- Delayed and prolonged- May stop bleeding and then restart- Clotting of small wounds is ok- Deep bleeds inside joings and muscles/following surgery and IM injections
106
Explain disseminated intravascular coagulation
Generalised activation of tissue factors inside the vasculature associated with sepsis and major tissue damage leads to widespread bleeding and consumption/deplteion of all coagulation factors and platelets
107
State the risk factors for thrombosis and the risk calculation
Risk Factors: age, pregnancy, immobilisation, oral contraceptibes, malignancy and surgery
Risk: multi-causal interaction of genetic and acquired factors, and will get thrombus when threshold reached
108
State Virchow's triad, whether each component affects venous/arterial circulation and causes of each
Triad: stasis (both ++), hypercoagulability (venous ++), endothelial injury (arterial ++)
Stasis: reduced flow caused by surgery, bed rest, flights or fractures
Hypercoagulability: anticoagulant deficiency (e.g. protein C/antithrombin) or increased coagulant proteins (e.g. FVIII, FII)
Endothelial injury: can happen in trauma, malignancy, infection or immune disorders
109
Decsribe the role of thrombolysis and how thromboli/emboli may be limited
Thrombolysis: used of tissue plasminogen activator to lyse fibrin, but carries high risk of bleeding Limitation:- Anticoagulant therapy - e.g. Heparin- Lower procoagulant factors - e.g. Warfain (oral and slow acting)- Inhibit FXa - e.g. Apixaban/Rivaroxaban
110
Define ejection fraction, give normal and abnormal ranges and state how this may be measured
Ejection fraction: SV/EDV
Measure with: transthoracic echocardiogram
Normal: >55%
Mild reduction: 45-54%
Moderate reduction: 30-44%
Severely reduced: <30%
111
Define heart failure
Clinical syndrome caused by inability of heart to supply blood to tissues sufficient to meet metabolic needs, or achieved at expense of filling pressures; causes inadequate organ perfusion and congestion in lungs/legs; often compensate with tachycardia
112
Differentiate between left and right heart failure
LHF: LV dysfunction leading to blood backing up into lungs causing pulmonary hypertension and oedema and hence respiratory Sx (SOB, coughing, wheezing and dizziness/cyanosis)
RHF: RV dysfunction due to increased afterload of pulmonary circulation (often 2/2 LHF) - need more oxygen but not supplied leading to ischaemic deathVentricle dysfunction may be related to ejection or filling
113
Differentiate between acute and chronic heart failure
Acute: rapid onset and quickly worsens
Chronic: slow-onset due to infection, PE, MI or surgery
114
Differentiate between heart failure with reduced and preserve ejection fractions
"HF w/PEF: abnormal diastolic function; ventricle contracts normally but increased stiffness/impaired relaxation reduces both the EDV and the SV; hypertrophy occurs inwards so that can't gain blood
HF w/REF: abnormal systolic function; ventricle cannot contract normally despire increased HR, decreasing CO due to damaged ventricular myocytes; reduces only the SV so can't expel blood
"
115
List the causes of heart failure in order of prevalance
1) Coronary Artery Disease: atherosclerosis and thrombosis of coronary arteries
2) Hypertension: increases afterload, causing hypertrophy, reducing space for filling, and increasing oxygen demand which may not be met
3) Cardiomyopathy: ventricle walls become thickened/stretched and so die
4) Valve Disease: mitral/tricuspid problems mean ventricles cannot fill with blood and pulmonary/aortic valve problems mean cannot expel5) Neoplasia/infection
116
List the clinical features, hallmarks and investigation of heart faliure
Clinical Features: orthopnoeas, exertional breathlessness, fatigue, ascites, tachycardia, reduced pulse volume
Hallmarks:
- Raised JVP: 2/2 increased right heart pressure
- Pitting oedema: fluid accumulation in tissue leads to pitting on depression
- Ascites: fluid in peritoneal cavity
Investigations: x-ray, ECG, ambulatory ECG and BNP
117
State the role of B-type naturietic peptide and testing for it
B-Type Natriuretic Peptide: released from ventricular myocytes in response to stretch - leads to microvessel vasodilation, reduced aldosterone secretion, reduced sodium reabsorption and inhibited renin secretion to reduce ECF and pressure
Testing: can be used as a clinical marker of heart failure
118
State the stepwise approach to medication in heart failure
1) ACE Inhibitor (or angiotensin receptor blocker if not tolerated)
2) Beta Blocker to decrease HR
3) Diuretic to reduce BP
Second line: valsartan to stop aldosterone production and ivabradine to vasodilate
119
Define the following types of cardiomyopathy: dilated, hypertrophic, restrictive, arrhythmogenic right ventricular
"Dilated: walls become stretched and thin so can't contract effectively - risk of HF and valve problems
Hypertrophic: walls become enlarged so chambers reduced in size; walls cannot properly relax
Restrictive: ventricle walls stiffened and cannot relax, so filling impaired - causes HF
ARVC: proteins holding together myocytes abnormal, leading to death and replacement with fat/fibrous tissue
Takotsubo: ""broken heart syndrome"" - emotional stress can stun left ventricle, so cannot contract effectively - cute no?
"
120
Explain the process of diagnosis and treatment for cardiomyopathy
Dx: ECG and echocardiogram
Tx: no cure, but lifestyle changes advised (smoking, alcohol, diet, stress, etc.) and can use diuretics, beta blockers and anticoagulants
121
State the modifiable and non-modifiable risk factors for atherosclerosis, and the epidemiology of these
Modifiable risk factors: smoking, lipid intake, BP, diabetes, obesity and sedentary lifestyle
Non-modifiable risk factors: age, sex, genetic background
Interaction: hypertension, smoking and high cholesterol produce x16 risk
Epidemiology: reduced population levels of hyperlipidaemia due to statins, and reduced hypertension due to antihypertensives means that plaques now primarily driven by obesity
122
Differentiate between LDLs and HDLs, and describe the structure of LDLs
LDLs: bad cholesterol - synthesised in liver, carried from liver to arteries (needed for normal function, so shows J-curve)
HDLs: good cholesterol - carrying from peripheral tissues to the liver
LDL Structure: has lipid monolayer and a docking molecule (apolipoproteins), with cargo fat (triglycerides and cholesterol esters) for fuel
123
Describe the localisation of atherosclerosis and the deposition/modification of LDLs
Location: at branching of vessels as turbulent flow/eddys form
Deposition: occurs into subinitimal space - binding to matrix proteoglycans
Modification: oxidised by free-radicals before phagocytosed by macrophages that become foam cells
124
Describe the two forms of macrophage scavenger receptors
MSR A: CD204, bind oxLDL, dead cells and gram positive bacteria to cause inflammation and destruction
MSR B: CD36, bind oxLDL, malaria parasites and dead cells for safe clearance and reverse cholesterol transport
125
State the roles of macrophages in atherosclerosis (4/5)
1) Generate free-radicals (NADPH oxidase and myeloperoxidase used)2) Phagocytose LDLs3) Express cytokines to recruit monocytes4) Express chemo-attractants 5) Express metalloproteinases - degrade wall of plaque to rupture and thrombose (degrade collagen)
126
Describe the characteristics of a vulnerable plaque and what happens upon rupture
Vulnerable plaques: large, soft, lipid-rich necrotic cores with reduced collagen content and a thin fibrous cap infiltrated by macrophages
Rupture: necrotic core meets blood as macrophages break down collagen to break fibrous cap causing thrombosis
127
Describe the overall progression of atherosclerosis and the window of opportunity to act
Progression: lesion-prone location accrues population of macrophage foam cells, dying to release fat; pools of extracellular lipids develop in wall and coalesce to form necrotic core, leading to fibrous thickening; if fibrous thickening not enough and cap cracks apart, triggers thrombus that can occlude artery; multiple events will lead to stratified appearance, with bleeding and clotting occurring cyclically, growing incrementally
Window of opportunity: lifestyle changes and risk factor management during intermediate/advanced lesion stage
128
Explain the following differentials of chest pain: ACS, Stable Angina, GORD, Pec muscle injury
Acute Coronary Syndrome: inadequate blood flow to heart muscle - includes MI and unstable angina
Stable Angina: inadequate blood flow to heart muscle precipitated by exertion and relieved at rest
Gastro-Oesophageal Reflux Disease (GORD): acidic stomach contents entering the lower oesophagus, causing heartburn
Pectoral muscle injury: strained/torn chest muscles that are painful upon use
129
Recall the investigations warranted for chest pain
ECG: identification of abnormal rhythms due to ischaemia or infarction
Troponin T: may be elevated in MI
Full history: needed to identify risk factors and behaviours e.g. Onset after exercise/long flight
130
Differentiate the descriptors, precipitants and risk factors of cardiac and non-cardiac pain
Cardiac: heavy, tight, dull, pressure; exercise + cold; smoking, stress, diabetes, FHx
Non-cardiac: sharp, stabbing, shooting; stress, posture, swallowing; pregnancy, food, obesity
131
Explain dietary and nutritional management of cardiovascular disease
(Fats): more monounsaturated/polyunsaturated fats and less trans/saturated fats
(Salt): less salt, because associated with increased BP (CVD that causes other CVDs)
(Fruit/Veg): every 1 portion of F/V lowers CHD risk by 4% and stroke risk 6%, as well as reducing BP
(Alcohol): very limited cardioprotective effects at low levels, decrease intake to reduce risk
132
Draw a cardiac cycle
1) ECG divided to 7 sections2) HS
3) Pressures (atria, aorta, ventricle)
4) Ventricle Volume
""
133
Recall the memory strategy for secondary haemostasis
1) 7a + TF2) 7 cat 9 + 103) 10 cat 24) 2 cat 85) 8 + 9 cat 106) 2 cat 57) 5 + 10 cat 28) 2 cat fibrinogen
134
Draw length-tension relationship diagrams for skeletal and cardiac muscle
"Only ascending limb of cardiac is important"
