Cystic Fibrosis

Question 1

Cystic fibrosis?

Answer 1

Defective Cl- transport across the cell membrane (usually this is regulated by transport channels)

Question 2

What is abnormal about this condition aside from the defective Cl-?

Answer 2

There is abnormal exocrine secretion (causes hyper secretion of fluid eg in the pancreas OR abnormal composition of secretion eg in the respiratory)

Question 3

Which systems do the abnormal exocrine secretions effect?

Answer 3

GIT, Respiratory system, reproductive tract

Question 4

Etiology of cystic fibrosis?

Answer 4

Cystic fibrosis transmembrane regulator gene on chromosome 7

Question 5

CFTR gene?

Answer 5

gene that codes for transport proteins

Question 6

What happens if the CFTR gene is mutated?

Answer 6

Transmembrane exchange is altered (specifically the exchange of chloride)

Question 7

What is the mode of inheritance in CF?

Answer 7

autosomal recessive -> requires 2 defective alleles (many people may be carriers, ie. have one defective allele, and may pass it on if they reproduce with another carrier)

Question 8

Which group is at increased risk of developing CF?

Answer 8

Caucasian people

Question 9

Which chromosome is effected by cystic fibrosis?

Answer 9

chr 7

Question 10

Explain the pathology of cystic fibrosis

Answer 10

CFTR codes for chloride channels on epithelial cell membranes. When there is a mutation the Cl- permeability is altered = impaired Cl- transport. Impact is tissue specific. Normally mucus is secreted into the lumen of the airway and contains Cl-, Na+, H20 and K+, BUT with a defective Cl- transport protein, mucus does not contain Cl-. Cl- builds up within the cytoplasm because it cannot be transported out and is in greater concentration within the cell than in the airway. Due to imbalanced concentrations on either side of the cell membrane, water is drawn out of the mucus and into the cell (as water always flows from areas of high to low solute concentration. Sodium always follows water, so Na+ is also drawn into the cell. This results in thick, viscous, sticky mucus lining the airway. Mucus obstructs the airway = compromised ventilation = decreased gas exchange

Question 11

What occurs to the tissue in CF?

Answer 11

It depends on which tissue is effected as impact is tissue specific

Question 12

Why is it problem when there is thick, viscous, sticky mucus lining the airway?

Answer 12

Because if the mucus is thick it will not be swept by cilia and remains along the lining of the airway, creating an ideal environment for microbial growth -> infection -> inflammation -> inflammatory damage

Question 13

What occurs as a result of inflammation in the previous case?

Answer 13

Vasodilation and hyperemia. Inflammatory cells release proteases which cause tissue destruction -> bronchiectasis, chronic bronchitis & resp failure are the cause of death in majority of CF patients

Question 14

What is the cause of death in majority of CF patients and what is the prevalence?

Answer 14

Bronchiectasis, chronic bronchitis & resp failure are the cause of death in majority of CF pts (>90%)

Question 15

Explain what happens in the respiratory system when a pt has CF.

Answer 15

• Thick mucus -> decreased ciliary function -> obstruct airway -> decreased breathing (dyspnea)
• Bacterial infection -> inflammation -> damage
• Hypercapnia & hypoxemia

Question 16

Explain what happens in the GI tract when a pt has CF.

Answer 16

Diarrhea, abdominal pain and abnormal pancreatic secretion

Question 17

Diagnostics of CF

Answer 17

• respiratory & GI mnfts
• Sweat test
• Trypsinogen blood test

Question 18

Explain the sweat test

Answer 18

The sweat test measures NaCl in a sample of sweat. The [NaCl] will be about 2-5 x higher than normal in a pt with CF.

Question 19

Why will the [NaCl] be 2-5x higher in a pt with CF?

Answer 19

Chloride is not withdrawn and for that reason, Na+ does not follow through. This is the reason why NaCl levels are higher in pts with CF

Question 20

Who is a trypsinogen test performed on?

Answer 20

Newborns - Screening test

Question 21

What secretes trypsinogen?

Answer 21

The pancreas

Question 22

Explain the trypsinogen test.

Answer 22

If a newborn has CF, their trypsinogen levels will be elevated because they have obstruction of pancreatic ducts -> obstruction of flow -> trypsinogen enters the blood

Question 23

Treatment for CF?

Answer 23

• no cure; intervention is largely supportive
• slow down progression (deal with complications)
• Diet modification (high protein, avoid fats) and pancreatic enzyme supplements d/t GI effects
• Mucolytics and chest physiotherapy
• Control/ prevent infection via Abx, gamma globulins
• DNAase

Question 24

Why are mucolytics given and phsyiotherapy suggested in pts with CF?

Answer 24

to help expectorate the mucus to increase gas exchange and decrease infection

Question 25

What does DNAase do?

Answer 25

It is an enzyme that breaks down DNA that is present in the mucus (d/t broken down to dead epithelial cells that have released their genetic contents) making mucus more mobile (helps with expectoration)