Link between Thyroid dysfunction and AF Flashcards
Name the 2 mechanisms that drive AF
- Formation of a re-entrant rhythm
- Increase in focal activity
both of these mechanisms are required for AF to occur
What is a re-entrant rhythm
Rhythm where the action potential, rather than passing through a group of muscle cells once and depolarising them and allowing them to contract, the action potential passes around the group of cells and continually stimulates them to generate action potentials
- can be local or global (Wolff-Parkinson white syndrome)
What is required for a re-entrant rhythm to occur
- changes in conduction velocity
- shortening of refractory period
what is increased focal activity
abnormal automaticity
- cells that normally can’t generate action potentials can suddenly do so
- some cells can generate multiple action potentials
What are the main cells which show automaticity
AVN and SAN
Describe the process of a normal rhythm (diagram)
- normally an action potential that is generated from SAN would come down and pass around the non conducting tissue and will eventually meet up at point 3 and cancel out
- this is because the cells have just been excited by the action potential and have a refractory period, so can’t be excited again
- so one action potential at the top will stimulate muscle cells to generate a single action potential
describe the process of a re-entrant rhythm (diagram)
- under conditions where the refractory period of tissue is shortened and there are conduction abnormalities, this can lead to an action potential coming down point 1, passing along the bottom and passing up slowly through point 2
- when it comes out the other side, it reaches a tissue that is recovered and is excitable again, so the action potential can go around and that can lead to a cell generating multiple action potentials
- each of these depolarisations will be allowing the muscle cells to contract
What 3 components need to match up in order to allow AF to occur
Refractory period
conduction velocity
distance around re-entrant loop
How would we aim to disrupt AF occuring
need to change refractory period and conduction velocity
what can be caused by abnormal automaticity
- Early afterdepolarisation
- Delayed afterdepolarisation
how does focal activity affect heart rate
Can increase sympathetic activity which increases heart rate by noradrenaline
or decrease parasympathetic activity which slows heart rate by Ach
What are early afterdepolarisations caused by
caused by an increase in action potential width (refractory period)
What are delayed afterdepolarisations caused by
caused by Ca2+ overload
Give an example of a drug that can caused delayed afterdepolarisation
digoxin
Give an example of a drug that can decrease automaticity and slow heart rate
Calcium channel blockers, beta blockers
Explain the pharmacological link between hyperthyroidism and AF
- An increase in sympathetic activity drives abnormal automaticity
- mechanism by which T3, the biologically active thyroid hormone can predispose patients to AF - T3 also decreases action potential duration which decreases refractory period of the tissue
- T3 increases the expression of a particular type of voltage gated K+ channel, allowing more K+ to leave
- bringing action potential back down to its resting membrane potential much quicker
Describe the pathway where T3 can drive focal activity
- Increased sympathetic tone
- T3 results in increased sensitivity to B1 adrenergic and decreased sensitivity to M2 muscarinic receptors
Describe the pathway where T3 can drive re-entrant rhythms
- Decreased Heart rate variability
- mediated by the vagolytic effects of T3
What would be demonstrated at the site of focal activity
demonstration of increased automaticity in pulmonary vein cardiomyocytes and increased incidence of supraventricular depolarisations
what is meant by remodelling
causing changes in heart muscle cells
What does ERP stand for
Effective refractory period
What 3 ways can remodelling occur
- ERP changes
- Conduction slowing
- atrial fibrosis
what is meant by conduction slowing
speed at which the action potential can pass through
what occurs in atrial fibrosis
muscle cells get smaller but connective tissue fills gaps
- connective tissue isn’t conductive