BMS303: Lecture 6 Sudden Infant Death Syndrome
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- Created by: Mollie
- Created on: 17-01-18 16:04
SIDS is mostly seen in infants under 1 y/o and accounts for 2500 deaths a year in the USA, how prevalent is it in developing countries?
It is the 3rd most common cause of infant death in developing ccountries
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List 4 risk factors associated with SIDS.
Male, 2-4 months, premature birth, low birth weight, parents from a low socioeconomic background, parents with low educational status, winter, overheating, mild viral infection, smoke exposure, parents taking drugs
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There are 4 main possible causes of SIDS; Cardiac ion channel mutations, autonomic disorders, metabolic disorders, Immunological polymorphisms. How may the later 3 each result in SIDS?
AD altering brain stem neurotransmitters & structures impacting sleeping pattern - stopping infant breathing while asleep, IMs may lead to altered inflammatory response. MD associated w/ liver abnormalities - changes in growth velocity & FA oxidation
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A study looking at the heart rate and QTc of babies who died from SIDS, other causes and normal were compared. HR similar in all conditions but average QTc of SIDS babies was on the upper limit of 2SDs from the mean of normal, what does this suggest?
Some SIDS have a normal QT interval however many have a prolonged QT interval which results in a mismatch in cardiac timings causing cardiac arrhythmias
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Research looking at rare and common variant mutations impacting Na channel SCN5A found some channels inactivated faster than WT but F1486L and F2004L inactivate slower, what are the consequences of slower inactivation?
Slower inactivating mutations prevent channel inactivation to the same degree as WT channels. Prolonged QT intervals are then created as a result of the persistent current
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How are delAL586-587 mutations in SCN5A Na channels characterised?
By increased Na currents and resulting difficulty for cell to repolarise
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In cells with R680H SCN5A mutant channels in what conditions is there an increase in Na currents and this faster channel inactivation?
When exposed to acidosis current more than doubles thus in intracellular acidosis there is a prolongation of the cardiac potential
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The Po of Kir6.1/KCNJ8 is regulated by ATP, the channel is found in the heart. What is the function of Kir6.1 in the heart?
It acts as a metabolic channel and helps the heart cope with stress
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Two mutations found on the carboxyl terminus of Kir6.1 channels are delE332 and V346I. What type of mutations and what are their implications?
delE332 and V346I are both loss of function mutations so channel currents were reduced . This resulted in a reduction in heart cells' ability to cope with metabolic stress and also has an impact on repolarisation which may result in SIDS
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Symptoms of Hypoxia present at teen years. Hypoxia and accompanied impact on pH lead to a reduction in blood oxygen which is small but enough to induce a cardiac event. What are some of these risk factors for hypoxia development?
Premature (major issue getting oxygen to tissue due to underdeveloped lungs), smoke exposure, prone position, mild viral infection
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The heart rate of mice increases after birth and their QT interval reduced. Upon experimentally exposing P0.5 - P10 mice to hypoxia what was observed?
There was an increase in QT interval, they also saw that the less time mice spent in normoxia conditions before 24h of hypoxia exposure the higher their death rate
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What was observed and concluded upon analysing the ECG of a mouse in hypoxic conditions?
Abnormal electrical activity due to mismatch between atria and ventricles. It has been suggested that hypoxia may also downregulate certain ion channels like KCNQ4 found on hair cells of inner ear
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Other cards in this set
Card 2
Front
List 4 risk factors associated with SIDS.
Back
Male, 2-4 months, premature birth, low birth weight, parents from a low socioeconomic background, parents with low educational status, winter, overheating, mild viral infection, smoke exposure, parents taking drugs
Card 3
Front
There are 4 main possible causes of SIDS; Cardiac ion channel mutations, autonomic disorders, metabolic disorders, Immunological polymorphisms. How may the later 3 each result in SIDS?
Back
Card 4
Front
A study looking at the heart rate and QTc of babies who died from SIDS, other causes and normal were compared. HR similar in all conditions but average QTc of SIDS babies was on the upper limit of 2SDs from the mean of normal, what does this suggest?
Back
Card 5
Front
Research looking at rare and common variant mutations impacting Na channel SCN5A found some channels inactivated faster than WT but F1486L and F2004L inactivate slower, what are the consequences of slower inactivation?
Back
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