Cystic Fibrosis

Question 1

1. Describe the genetics of cystic fibrosis.

Answer 1

autosomal recessive, occurring 1 /4,000 births; approximately 1/29 Americans are carriers

gene is located on the long arm of chromosome 7

most common mutation is deltaF508 (70% all mutations)

Question 2

2. Explain the normal mechanism of the cystic fibrosis trans- membrane regulator protein and its dysfunction in cystic fibrosis.

Answer 2

cystic fibrosis transmembrane regulator protein has 2 transmembrane regions (6 trasmembrane loops), 2 intracellular nucleotide binding folds and one regulatory domain with potential phosphorylation sites

the deltaF508 mutation results in the deletion of phenylalanine which alters protein function and sometimes protein is not synthesized

Question 3

3. Describe the pathophysiology of cystic fibrosis in different organ systems (GI) and the resulting clinical manifestations.

Answer 3

GI: blocked pancreatic ducts (cystic dilation and fibrosis), malabsorption due to pancreatic insufficiency, and increased gallstones and DM; some cases liver cirrhosis

Question 4

4. Describe and explain the pathologic changes and the changes in lung mechanic and gas exchange that occur over time in cystic fibrosis.

Answer 4

1. defective CF gene
2. deficient/defective CFTR protein
3. decreased chloride secretion and increased sodium absorption
4. bronchial obstruction
5. infection
6. inflammation
7. airway destruction

ongoing massive inflammatory response ultimately destroys the airways, impairs gas exchange resulting in ventilation/perfusion mismatch and leads to death , FEV1 continues to decline throughout life and is the single best predictor of mortality, FEV1 fallen to 30% of predicted, 2yr mortality is about 50%

Question 5

5. Discuss the gross and histological changes that occur in the lungs of patients with cystic fibrosis.

Answer 5

gross: widespread bronchiectasis with purulent mucus in airways, interstitial air or concomitant emphysematous bullae, lobar atelectasis, consolidation with abscess and pleura showing evidence of adhesions and or fibrosis
histology: dense acute and chronic inflammation with luminal purulent mucous plugging, airways with squamous and or goblet metaplasia, mucous plugging, evidence of pneumonia or abscess formation with interstitial fibrosis and inflammation

Question 6

6. Define the presentations of cystic fibrosis in the respiratory and GI systems, and be aware of other consequences that can result because of cystic fibrosis.

Answer 6

chronic cough, wheezing, recurrent pneumonia, sinusitis, nasal polyps, bronchiectasis, clubbing

prolonged jaundice of infancy, meconium ileum, steatorrhea, rectal prolapse, failure to thrive, recurrent abdominal pain, distal intestinal obstruction syndrome, edema, hypoporteinemia and anemia, portal hypertension

pseudo tumor cerebra due to vit. A deficiency, tastes salty when kissed, male sterility, hyponatremic hypochloremic metabolic alkalosis, anemia due to vitamin K deficiency

Question 7

7. Analyze diagnostic testing results of cystic fibrosis.

Answer 7

sweat test by quanitative pilocarpine inotphoresis: sweat chloride greater than 60mEq/liter is abnormal and positive for cystic fibrosis

Question 8

8. Understand the principles of management for a patient with cystic fibrosis.

Answer 8

pancreatic enzymes
vitamins
high calorie diet
airway clearance 
antibiotics
bronchodilators as indicated

Question 9

3. Describe the pathophysiology of cystic fibrosis in different organ systems ( sweat glands) and the resulting clinical manifestation.

Answer 9

sweat glands: decreased reabsorption of sodium and chloride (resulting in salty sweat), nonspecific irritating rash and dehydration that is hyponatremic and hypcholermic with metabolic acidosis

Question 10

3. Describe the pathophysiology of cystic fibrosis in different organ systems (reproductive) and the resulting clinical manifestation.

Answer 10

males: sterility due to absence of Wolffian duct structures- bilateral absence of vas deferens
females: fertility decreased due to thick secretions blocking the cervix (30% reduction in fertility)

Question 11

3. Describe the pathophysiology of cystic fibrosis in different organ systems (respiratory) and the resulting clinical manifestation.

Answer 11

initial colonization with Staphylococcus aureus followed by Pseudomonas aeruginosa- pretty unique to CF

inflammation develops due to WBC and other immune system defenses, cycle of inflammation, infection and mucus production results in progressive airway obstruction, hyperinflation and increased incidence

can lead to pulmonary hypertension and eventually for pulmonale