Multisystem Diseases

Question 1

Cystic fibrosis genetics

Answer 1

Autosomal recessive.
Defect CFTR gene - chromosome 7.
Commonly deletion of Phe508.

Question 2

CF pathogenesis

Answer 2

CFTR encodes ATP-gated Cl channel that secretes Cl- in the lungs and GI tract and reabsorbs Cl- in sweat glands.

Mutation–> misfolded protein –> protein retained in RER –> dec Cl-and H2O secretion.
^Cl intracellularly –> ^Na+ reabsorption (via epithelial Na+ channels) –> ^H2O reabsorption –> thick mucus secreted in lungs and GI tract.
^Na+ reabsorption –> more negative trans epithelial potential difference.

Question 3

CF diagnosis

Answer 3

^ Cl- concentration in sweat (>60).
Can present with contraction alkalosis and hypokalemia bc of ECF H2O/Na losses and renal K+/H+ wasting.
^ immunoreactive trypsinogen (newborn screening).

Question 4

CF complications

Answer 4

Recurrent pulmonary infections
-S aureus: early infancy
-Pseudomonas: adolescence
-chronic bronchitis and bronchiectasis –> reticulonodular pattern CXR
Pancreatic insufficiency, malabsorption w steatorrhea, fat-soluble vitamin deficiencies (A, D, E, K), biliary cirrhosis, liver disease, meconium ileus in newborns.
Infertility in men (absence of vas deferens) and sub fertility in women (amenorrhea, thick cervical mucus).
Nasal polyps, nail clubbing.

Question 5

CF treatment

Answer 5

Chest physiotherapy, albuterol, aerosolized dornase alfa, hypertonic saline - mucus clearance.
Azithromycin - anti-inflammatory.
Pancreatic enzymes - insufficiency.