Cystic Fibrosis

Front 1

What is cystic fibrosis?

Back 1

a heterogenous recessive genetic disorder affecting mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR)

Front 2

Classic cystic fibrosis?

Back 2

chronic bacterial infection of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males and elevated levels of chloride in sweat

Front 3

Non classic cystic fibrosis?

Back 3

patients have at least one copy of a mutant gene that confers partial function of the CFTR protein, and such patients usually have no overt signs of maldigestion because some pancreatic exocrine function is preserved

Front 4

Where is the CFTR gene located?

Back 4

7q31.2 chromosome

roughly 250,000 base pairs long

Front 5

Where are normal CFTR proteins found?

Back 5

normal CFTR protein is a chloride channel protein found in membranes of cells that line passageways

lungs

liver pancreas

digestive tract

reproductive tract

skin

Front 6

CFTR protein made up of five domains?

(the most common CF causing mutation [delta F508] occurs in the DNA sequence which codes for the first nucleotide binding domain)

Back 6

two membrane spanning domains the form the chloride in channel (MSD1 and MSD2)

two nucleotide binding domains that bind and hydrolyse ATP

a regulatory R domain

Front 7

How many classes of CF mutations?

Back 7

class 1 - premature stop mutations producing truncated mRNA

class 2 - misfolded and unable to escape the ER

class 3 - channel is not properly activated

class 4 - decreased chloride conductance

class 5 - decreased abundance of CFTR

Front 8

Normally functioning mucus clearance system requires?

Back 8

mucus secretion

salt and water transport

cilial beating

Front 9

Define ASL

Define PCL

Back 9

Airway surface liquid

Periciliary liquid layer

Front 10

Clearance of mucus depends on?

Back 10

ciliary function

mucin secretion

volume of airway surface liquid

Front 11

CF therapy?

Back 11

airway clearance - bronchodilators, dornase alfa

infection - inhaled, IV, oral

gastrointestinal - pancreatic supplements

inflammation - ibuprofen

Front 12

Major component of mucus in CF?

Back 12

pus that includes viscous material such as polymerised DNA derived from degraded neutrophils

Front 13

Only mucolytic agent with proven efficacy in CF?

Back 13

dornase alfa - reduces pulmonary exacerbations and improves lung function

Front 14

Thickened secretions on the pancreas...

Back 14

block pancreatic exocrine movement of the digestive enzymes into the duodenum resulting in irreversible damage to the pancreas and painful inflmmation

Front 15

Lack of digestive enzymes leads to?

Back 15

difficulty absorbing nutrients (malabsorption)

occurs in 85-90% of CF patients

Front 16

Common bacterial lung infections in CF?

Back 16

Staphylococcus aureus

Pseudomonas aeruginosa

Front 17

Infections in CF...

Back 17

infection triggers inappropriately robust response including excessive release of neutrophils which release mediators that damage cells and thicken secretions.

the vicious circle of sputum retention, infection and inflammation perpetuates itself because inflammatory products released by neutrophils stimulate mucus secretion and mucus breakdown

Front 18

Common treatment for chronic infection?

Back 18

high dose of tobramycin proven to be effective

Front 19

Major goal in treating CF is to?

Back 19

clear the abnormal and excess secretions and control infections in the lungs and to prevent obstruction in the intestines