W21 - Cystic Fibrosis

Question 1

what is cystic fibrosis

Answer 1

a genetic autosomal recessive, systemic and multiorgan disease caused by defective ion transport

involves imbalance of fluid and electrolytes causing thick, sticky mucus and viscous secretions to accumulate in different organs

Question 2

in what ethnicity is cystic fibrosis most common

Answer 2

caucasian

Question 3

how deadly is cystic fibrosis

Answer 3

most lethal genetic autosomal recessive disease in the white population

Question 4

What is cystic fibrosis caused by

Answer 4

mutation in a gene that encodes cystic fibrosis transmembrane conductance regulator

a chloride channel expressed in epithelial cells and other type of cells

Question 5

what is autosomal mean

Answer 5

refers to any chromosomes other than the sex determining chromosomes

Question 6

what does recessive mean

Answer 6

not expressed unless both copies are present

Question 7

what does autosomal dominant mean

Answer 7

a gene on one of the non sex chromosomes that is always expressed, even if only one copy is present.

Question 8

where is the CFTR located

Answer 8

apical membrane of secretory and absorptive epithelial cells of the pancreas, intestine, liver, airway, vas deferens and sweat glands + sweat glands.

Question 9

What is the function of the CFTR protein

Answer 9

cyclic AMP dependent chloride channel, a bicarbonate channel and as a modulator of other ion channels

Question 10

what does CFTR stand for

Answer 10

cystic fibrosis transmembrane conductance regulator

Question 11

what is the CFTR

Answer 11

cloride channel expressed in epithelial cells that maintains

salt
fluid
pH homeostasis in various epithelial tissues

Question 12

how do CFTRs form a pore

Answer 12

line up in parallel tail to tail forming a pore at its centre

Question 13

What does NBD stand for

Answer 13

Nucleotide binding domain

Question 14

what does RD stand for

Answer 14

Regulatory domain

Question 15

Describe the role of NBD + RD in the channel

Answer 15

NBD + RD are in the cytosol and the membrane domain form the pore of the channel. RD is phosphorylated by a cAMP dep kinase, NBDs bind to and hydrolase ATP providing energy to open and close the pore.

Question 16

what is the major NBD + RD function

Answer 16

regulating chloride conductance

Question 17

What symptoms exist of pulmonary disease

Answer 17

copious sputum production 
persistent cough
reduced lung function 
inflammation and tissue damage
chronic airway infections

Question 18

what is the main cause of morbidity and mortality of CF

Answer 18

chronic lung disease

Question 19

what are 2 forms of pancreatic dysfunction

Answer 19

exocrine pancreatic insufficiency - impaired enzyme secretion from pancreas and malnutrition

endocrine pancreatic insufficiency - cf related diabetes mellitus

Question 20

what effect does CF have on pancreatic secretions and the pancreas itself

Answer 20

pancreatic secretions have lower fluid volumes and increased acidity within the pancreatic lumen which leads to precipitation of the protein rich secretions which can cause plugging of small ducts and obstruction. Meaning more damage to pancreas.

Question 21

what is Meconium ileus

Answer 21

20% of babies with CF have this, it is a condition where the content of the newborn child’s bowel (meconium) is extremely sticky and causes the bowel to be blocked at birth.

Meconium ileus is a bowel obstruction that occurs when the meconium of child intestine is even thicker and stickier than normal.

Question 22

What are some gastrointestinal symptoms

Answer 22

thickened intestinal secretion, malabsorption, malnutrition, decreased gut motility. Salty tasting skin. Congenital absence of the vas deferens

Question 23

what can result from a mutation of the CFTR

Answer 23

reduce transcription or translation

affect traffinking to surface

accelerate protein turnover

causes loss of protein

Question 24

what are two ways in which we test for CF

Answer 24

blood test in new borns

sweat test in child / adult

Question 25

Describe the pathophysiology of CF

Answer 25

CFTR gene defect

Defective ion transport

• lower chloride transport
• higher sodium absorption
• higher h20 absorption

airway surface liquid depletion

defective mucociliary clearance

mucus obstruction

infection

inflammation

Question 26

At what point in the pathophysiology can we try and manage

Answer 26

Potentiators and correctors can be used at airway surface liquid depletion

mucoactives and physiotherapy can be used at mucus obstruction

immunomodulatory therapy, antimicrobial

Question 27

what are mucoactives

Answer 27

increase the ability to expectorate sputum and or decrease mucus hypersecretion

Question 28

What are the 4 types of mucoactives

Answer 28

expectorants (induce cough or increase the volume of secretions)

mucolytics (reduce the viscosity of mucus)

mucokinetic drugs (increase the mobility and transportability of mucus)

mucoregulators (control the process of hypersecretion)

Question 29

what is an example of first line mucoactives

Answer 29

inhaled recombinant human DNase I degrades DNA

Question 30

What is ivacaftor (kalydeco)

Answer 30

conductance regulator potentiator for CFTR channel with a G551D A “missenge” gating mutation. Ivacaftor increases the time the mutated CFTR is open, allowing chloride ions to flow through. This action partially normalises the consistency of mucous and digestive juices in cystic fibrosis.

Question 31

what is lumacaftor

Answer 31

channel corrector

Question 32

what is a channel corrector

Answer 32

acts as a protein folding chaperone, aiding the conformational stability of the mutated CFTR protein.

Question 33

what is the purpose of chest physiotherapy

Answer 33

to augment clearnace of tenacious airway secretions

Help postural drainage and percussion in varied positions that help draining mucus, chest is clapped and vibrated to help dislodge mucus to large airwayts

Question 34

what is postural drainage

Answer 34

positions to help drain mucus