channelopathies Flashcards
define channelopathies
- improper function of the heart as a reault of mutations to proteins that make up the ion channels in the heart
- each ion channel can be associated with a channelopathy
define cardiomyopathies
physcial change in the structure of the heart muscle due to the inability of the heart to properly pump blood
what does the cardiac action potential represent?
represents the total electricity of an individual cardiomyocyte undergoing a contraction (essential)
what contributes to the formation of the cardiac action potential? why is this important?
- ion channel composition of each cardiac cell
- important for propogation of excitation
what are the major ion channels?
Ca, K, Na
how are channelopathies typically diagnosed?
-through the use of ECG recordings (present a map of electrical impulse throughout the heart)
what is the pathophysiology of a normal patient compared to one with long QT syndrome?
- normal: arterial depolarization (P wave), ventricular depolarization (QRS complex) and ventricular repolarization (S-T wave)
- LQTS: have a long QT interval (can differ btwn patients)
what can LQTS lead to if left untreated?
uncoordinated heart muscle function and fatal cardiac arrythmias
what the definitive mutations associated with LQTS?
- KCNQ1 (first & definitive) (LQT1)
- KCNH2 (LQT2)
- SCN5A (LQT3)
is clinical lab testing offered for all genes associated with LQTS?
no, only the three w a defenitive connection
locus and clinical _____ is associated with LQTS?
explain.
heterogeneity
- locus: each of the channelopathies may be caused by multiple mutations
- clinical: mutations in many of these genes have a role in more than one of these channelopathy subtypes
explain LQT1 (mutation and cause of cardiac arythmia)
- mutations occur in the KCNQ1 gene (35%)
- this type causes cardiac arythmias while participating in physcial activity
explain LQT2 (mutation and cause of cardiac arythmia)
- mutations occur in the KCNH2 gene (30%)
- this type is most commonly caused by auditory triggers as well as the postpartum period
explain LQT3 (mutation and cause of cardiac arythmia)
- mutations occur in the SCN5A gene (10%)
- often die during rest (most often assoicated with sudden infant death syndrome)
the younger somone passes away from LQTS suggests:
it was an inherited condition
define penetrance
the extent to which an individual will develop some aspect of the disease if they possess a mutation in the disease causing gene
define expressivity
the presentation of the disease/the intensity of the phenotype
100% penetrance and constant expressivity means
every person with the mutation will display the same symptoms of the channelopathy of interest
<100% penetrance and constant expressivity means
not every family member with the mutation will display symptoms associated with the disease but if they do they’ll be the same as all other family members
<100% penetrance and variable expressivity means
not every family member with the mutation will display the symptoms and if they do they will show a variety of symptoms throughout the family
list factors that could result in variable expressivity
- genetic background
- environmental influences
- lifestyle
lower penetrance makes it harder to associate between the disease and the gene, true or false?
true
define benign genomic variants
genomic variant that does not increase a patients susceptibility to a disease/disorder
define a genomic variant with unknown significance
genomic variant that has an unknown effect on the patients susceptibility to a disease/disorder
define a pathogenic genomic variant
genomic variant that is known to increase a patients susceptibility to a disease/disorder
is measuring a patients QT length a definitive method for diagnosis LQTS? why or why not?
- no
- research has shown an overlap in QT length between normal non-carriers and LQTS mutation carriers
explain LQTS risk stratification
why do we do this?
- can’t just identify mutation and properly diagnose
- patients are risk stratified based on gender, QT interval, type of LQTS, genotype and presence of mutation(s)
what are the two primary stategies for treating channelopathies? is treatment of this disease important?
yes bc risk of sudden death
(1) arrythmia prevention
(2) arrythmia termination
explain the process of arrythmia prevention.
what are the limitations to this method?
- perscribe beta-blockers
- work to limit adrenergic stimulation that can provoke arrythmia
- limitations = cause fatigue (don’t do exercise), leads to poor compliance (especially in younger ppl)
explain the process of arrythmia termination
- implantable cardioverter-defibrillator (ICD) can be used to deliver elctrical shock to the heart
- wires link from heart to device and detect normal rythm
- if arrythmias arise: provides shock to heart to reset
- not always effective but has saved many
