Pathophysiology of ENaC Flashcards
The airway surface layer is divided in to
1) The true liquid layer
2) The mucous layer
What is the role of the mucous layer?
It is the first line of defence against respiratory pathogens
Describe the problem of volume load in the movement of ASL in the lungs
The alveoli have a large surface area, however this decreases up the lungs
This means we have the same amount of liquid over 50cm2 rather than 200cm2 up the respiratory tract
This means the height of the ASL would have to rise which would affect cilia movement if it is higher than the optimum and mucous would not be cleared effectively
Describe two ways it is thought that the ASL can be controlled
1) Passive - the mucous layer acts as a reservoir e.g. if the height of the liquid layer is too high then water will move in to the mucous layer
2) Active - Active ion transport where the concentration of salt is controlled in the liquid layer which subsequently controls how much water is in the liquid layer
Describe an in vitro experiment which shows the airway surface layer has an optimum height
Fluid was added to the top of cells (epithelia) so that the height was higher than the optimum (30ul)
The height of the layer went down over time to 7 ul where the height remained constant
What is the optimum height in vitro?
14 ul
What does amiloride block?
ENaC
What does bumetanide block?
NKCC1
What is the effect of bumetanide?
It blocks NKCC1 on the basolateral membrane which inhibits chloride secretion
Describe an in vitro experiment which shows the mechanisms involved in maintaining the optimum ASL height
Amiloride and Bumetanide was used and they looked at how much each blocked the Vte at time zero and at time 48 hours
e.g. on the graph bigger bar = bigger inhibition
Amiloride - at time zero amiloride gave 60% inhibition of the Vte which suggests lots of sodium is being reabsorbed so water follows = decrease in height
At 48 hours this had been down regulated
Bumetanide - at time zero only around 18% if the Vte was generated by chloride secretion but after 48 hours bumetanide inhibited around 50% of the Vte
Describe what the experiment with amiloride and bumetanide shows about the control of the ASL
When the ALS height is too high than Na+ reabsorption is greater than Cl- secretion
When the ALS height is too low then C;- secretion is greater than Na+ reabsorption
It also shows that the balance between the two is important for maintenance of the ASL height
Why is ENaC important at birth?
It is important for lung clearance at birth i.e. amniotic fluid needs to be cleared
Describe the cell model for the cells in the upper airway respiratory tract
Apical - ENaC, cilia and CFTR
Basolateral - Na+/K+ ATPase, NKCC1, potassium channel
1) K+ channel and ATPase set up the driving force for Na, 2Cl and K to move in to the cell through NKCC1
2) Na and K recycle = Cl accumulates
3) CFTR opens = cl secretion
What is RSV?
Respiratory syncitial virus
What are the symptoms of RSV?
Nasal congestion, bronchiolitis in children and pneumonia in adults
Major respiratory pathogen in children = 20% of hospital admissions