Cardiovascular Flashcards
Definition of preload
The load on the myocardium that determines the initial stretching (or fibre length) of the
cardiac myocytes prior to onset of contraction (Ie. end-diastole)
(LVEDV or LVEDP)
What are the indices of preload (how can we roughly estimate it)?
Cannot be directly measures. Can be indirectly determined using either:
- LVEDV: visualised with TTE
- LVEDP: can be measured using:
—– LA pressure from Left heart cath (LAP ≈ LVEDP)
—– Pulmonary capillary wedge pressure (PAP ≈ LAP ≈ LVEDP)
—– RA pressure or CVP (via a CVC line) – RV preload is assumed to be similar to LV preload
What are the factors that determine preload:
1) CVP
- venous compliance (venoconstriction = increase CVP)
- Thoracic venous blood:
— Total blood volume
— venous return (aside from TBV, i.e head down, respiration, muscle contraction)
2) Ventricular compliance - increase compliance = increase expansion and filling
3) Atrial contractility - (increase SNS, increase atrial filling) = increase vent filling
4) HR - tachycardia reduces ventricular filling time
5) Aortic pressure - increased afterload = reduced SV and therefore increases ESV. increased ESV –> increased LVEDV.
6) Pathological conditions
- increase preload with:
—- Ventricular failure (increase ESV)
—- outflow valve stenosis or regurge (AS/AR)
— inflow valve regurge (MR)
Definition of afterload
Ventricular wall stress encountered as a result of the resistance that the ventricle must
overcome for it to eject its contents into the arterial circulation during systole (Ie. following isovolumetric ventricular contraction and opening of the aorto-pulmonary valves)
What are the indices of afterload (how can we roughly estimate it)?
Using law of LaPlace ventricular wall stress can be determined. As wall tension = Ventricular pressure x radius)
Wall Stress = wall tensions / 2xthickness
Therefore stress (afterload) = pressure x radius / 2 x thickness.
Using this stress (afterload) is indirectly measured by the ventricular pressure during systolic ejection (≈ aortic pressure, UNLESS AS is present) – Clinically this is estimated by the systolic arterial BP (or more commonly the MAP)
What are the determinants of Afterload
See deranged physiology
Think LaPlace for wall stress = transmural pressure x radius /2thickness
radius = ventricular EDV
Thickness = wall thickness
Transmural pressure can be broken into :
- intrathoracic pressure (negative vs positive)
- outflow impedence (HOCM/stenosis)
- inflow inpedence:
— arterial compliance
— arterial resistance: hagen poiselle
—- length
—- viscosity
—- radius^4
Compare the determinants of afterload for LV and RV
Table:
What are the components of the myocardium
Cardiomyocytes
Extracellular connective tissue (ECM)
Conductive tissue
What are the components of a cardiomyocyte
Myofibrils - rod bundles responsible for contraction. Made up of contractile proteins, regulatory and structural proteins
Organelles like nucleus, mitochondria, sarcoplasmic reticulum, cytosol
Sarcolemma: outer plasma membrane separating intracellular and extracellular space
What is the sarcoplasmic reticulum
organelle of cardiomyocyte that stores and releases calcium
Junctional SR: releases Ca stores in response to depolarization stimulated Ca influx through sarcolemmal Ca channels (via ryanodine receptors RyR)
Longitudinal SR: involced in uptake of Ca+ for initiation of relaxation.
What are the components at cardiac intercellular junctions
Gap Junctions (made of connexin), involved in electron coupling and transfer of small molecules between cells
Spot desmosome anchor the cytoskeleton of the cell
and sheet desmosomes which link contractile apparatus. (so they contract together)
How are purkinje cells different to other cardiomyocytes
Purkinjie cells are conducting cardiomyocytes, specialised for conducting action potentials
They have low content of myofibrils, a prominent nucleus and contain abundance of gap junctions (for quick transmission of AP)
Their function is to propagate AP to individual cells
What are he types of action potentials and where are they found
Fast-response: His, Purkinjie. or atrial/ventricular cardiomyocytes
Slow response: pace-maker cells - SA and AV node
(Big question) (draw) What are the four phases of a fast response action potential, what is the movement of ions at each phase,
Phase 4: Resting membrane potential -90mV (discuss Nearnst potential late). Ionic concentrations restored by Na+/K+/ATPase (gets rid of Na from depolarisation and restores K+ from rep) and Na+/Ca+ exchange. Na channels are at resting state
Phase 0: Rapid depolarisation:
- when membrane potential gets to -65-70mV, fast VG NA+ channels open, trigger influx of Na into cell. depolarising to +20mV. (short time as channels are time limited (few ms)
triggers VGCa channel to open, but influx of Ca is much slower.
Phase 1: partial/early repolarisation
- VGNa Ch close, chemical/electrostatic force promote K+ efflux out VGK ch
Slow opening L-type Calcium channel open (K+ outweighs Ca coming in) MP goes to 0.
Phase 2: plateu phase:
- Ca influx though L Ca Ch = K+ out thru VGKaCh. MP remains at 0
- Na channels stay closed fast-inactivated state
Phase 3: replorasation:
- L type Ca Ch shut. no more Ca in.
- outgoing K+ efflux thorugh VGKaCh to return MP to -90.
What are the states of a voltage gated sodium channel
1: Resting: Activation gate closed due to membrane potential.
2: Active: open during phase 0 depolarisation
- open activation gate, and open inactivation gate
3: inactive: inactive at positive potential (0) and with marked depolarisation (2). cant be activated until returned to RMP, returns to resting state.
What are the refractory periods of the cardiac cycle
Absolute refractory period (phase 0,1,2) where the cell is unable to be excited.
Extended refractory period is ARP + a brief time where cell can be excited but cannot propogate and action potential
Relative refractory period, some of the VGSC are back in resting state so the cell can be stimulated but it creates a weak AP that propagates slowly.
Supranormal period: very brief period before resting state where a weaker than normal stimulus can trigger an AP.
Where /what phases in the fast-response action potential do different classes of anti-arrhythmics work
Class 1 works at phase 0 (Na Ch blocker)
Class 2 works at Phase 4 (B-Blocker)
Class 3 works at phase 3 (K+ channel blocker)
Class 4 works at phase 2 (Ca ch blcoker)
Think about them rotating anti-clockwise to the phases (if that makes sense)
(Big question) (draw) What are the four phases of a Slow response action potential, what is the movement of ions at each phase
Phase 4: unstable membrane potential at -60mV up sloping. gradual spontaenous depolarisation due to Funny currents. Na channels activated by hyperpolarization. RMP becomes less negative
Calcium starts to come in at around -50mV (T-Type channels - transient and short acting) - helps further depolarise cell
at -40mV VGCC (L-type start to open - but theyre slow)
VGKC continue closing, less K+ leaving the cell.
Phase 0:
- once -40mV reached, L-Type CC are open and cell is depolarising (slower rate compared to fast Na channels)
- T type CC and Na funny currents close.
no phase 1 or 2
Phase 3: Repolarisation
- K+ Ch open, K+ leaves
- inactivation of Ca+ (Ltype)
What are the intervals of the ECG, their normal durations, and respective events during the heart
PR: 120-200ms. Depolarisation of Atrtia
QRS: up to 100ms. Ventricular depolarisation and atrial repolarisation
QT: up to 430ms. (QTc 360-450ms) Ventricular depolarisation and repolarisation
ST: (average 320ms), ventricular repolarisation (during T wave)
What is ECG measuring
Vector sum of electrical activity
Magnitude + direction (therefore = vector)
What are the leads of an ECG
12:
Limb leads:
Bipolar 1,2,3. +ve to -ve
UniPolar aVR, aVL, aVF. (the -ve is the average of the two negative nodes)
- aVR R arm is positive
- aVL L arm is positive
- aVF left Foot is positive
Pre-cordial leads V1-V6
What is Einthoven’s Triangle
An imaginary triangle created by the 3 electrodes at the left arm, left leg and right arm used to determine the axis of the heart.
What will prolong PR interval
PNS: increase PNS –> increase ACh from vagus –> bind to Cardiac M2 receptors (GiPCR) –> reduce cAMP –> reduce conduction velocity
ACH also increases membrane K+ permeability, increase K+ out of cell which hyperpolarizes it, slows conduction velocity
Drugs: cholinergics, CCB, beta blockers, adenosine, digoxin
Physiological: hypokalaemia, hypothermia, hypothyroidism, hyper or hypo Mg
Cardiac disease: ischaemia, hypoxia (slows cuntion velocity)
What shortens PR interval
SNS: increase SNS –> increase cAMP –> increase intracellular ca –> increase AVN conduction velocity
increase calcium also reduces RMP. facilitates depolarisation and quicker conduction velocity.
Drugs: sympathomimetics, anticholinergics: increase membrane Ca+ permeability and excitability
Physiological: hyperthyroidism
Cardiac: accessory pathways (WPW syndrome)
