CF

Question 1

What is CFTR responsible for?

Answer 1

Controls movement of Cl- ions, in turn these control movement of water into tissues - necessary for thin mucus production.
Also regulates function of other channels such as Na+ and can move bicarbonate across the cell.
Also reduces glutathione

Question 2

What is FEV1 and FEV1%?

Answer 2

FEV1 = volume exhaled at the end of the first second of forced expiration. 
FEV1% = FEV1 of patient divided by FEV1 in population for any person of similar age, sex, body composition.

Question 3

What factors contribute to the decline in lung function seen in CF patients?

Answer 3

• Recurring bacterial infection (thick sticky mucus).
• EFA deficiency
• Protease / anti-protease imbalance.
• Increased OS.

Question 4

How do immune cells release proteases and damage anti-proteases?

Answer 4

Neutrophils release elastase

HOCl exacerbate by oxidising critical met residues in alpha1-protease inhibitor.

Question 5

Give three sources of ROS in cystic fibrosis.

Answer 5

Increased O2 consumption by fibroblasts
Theophilline - increases P450 activity –> generates superoxide.
Ps Aeruginosa - releases Pyochelin and Pyocyanin - redox cycle in lung cells and produced free radicals.

Question 6

How do neutrophils contribute to ROS generation?

Answer 6

Secrete more MPO and elastase –> altered cytokines production and dysregulated chemotactic response.
Release a large amount of ROS via NOX
Frustrated phagocytosis can result from continuous interaction of neutrophils with bacteria/ degradation products.