Cystic Fibrosis

Question 1

CFTR present in what epithelial cells

Answer 1

pancreas
salivary glands
sweat glands
intestine
respiratory 
reproductive

Question 2

CFTR

Cystic Fibrosis Transmembrane conductance Regulator gene

Answer 2

ATP binding cassette transport
-protein kinase A
ATP regulated chloride channel
regulatory protein for other channels
only 5-10% activity needed for normal chloride transport

Question 3

Muations are closely linked to infertility and pancreatic function but not to what?

Answer 3

pulmonary function

Question 4

Delta F 508

Answer 4

88% of all CF patients have on copy of delta 508

• 3 base deletion at position 508 remove a phenylalanine
• protein does not escape ER for further processing
• dependent on ethnicity

Question 5

WHat happens in class 1,2,3,4,5 mutation?

Answer 5

1-no synthesis
2-no maturation deltaf508
3-blocked regulation-G551D
4-decreased conductance
5-decreased abundance

Question 6

Airway surface liquid is thought to be:
ASL low volume or ASL too salty
how does this work?

theres also:
abnormal submucosal gland secretion
abnormal modulation of epithelium inflammation

Answer 6

asl low volume-mucus stasis decreased ciliary beat-inhibited bacterial clearance
-major defect in lack of regulation of ENaC, Na is hyper-absorbed, cl follows through other pathways, water follows passively–>low volume increased mucus, delayed transport, mucus adhesion

asl too salty-salt sensitive defensins don’t work
-chloride can’t be reabsorbed, sodium and water reabsorption also decreased

Question 7

CF lungs normal at birth

Answer 7

yes
-secretions and clearance is abnormal leading to inflammation, chronic infection, obstruction, bronchiolitis and bronchiectasis

Symptoms-Chronic productive cough, dyspnea, chest tightness
-can have hemoptysis, pneumothorax as complication

Question 8

What does a CF-CXR look like?

Answer 8

upper lobe predominant bronchiectasis
-sgnet sign
-tram tracking
peribronchial cuffing
nodules/mucous impaction
blebs, cysts

Question 9

What respiratory infections are high?

Answer 9

Staph then pseudo
Pseudo chronic infection changes:
-biofilm
-lps changes
-loss of flagella dependent motility 
-slower growth

Question 10

What respiratory infection is associated with rapid decline?

Answer 10

burkholderia cepacia

Question 11

How does CF affect the sinus?

Answer 11

hypertrophy/hyperplasia of secretory elements

• inflammation and edema
• polyps
• transepithelial electric potential raised

Question 12

How does CF affect the GI?

Answer 12

meconium ileus
distal intestinal obstruction syndrome
rectal prolapse
focal biliary cirrhosis
hypoplastic GB, gallstones
fatty liver

Question 13

How does CF affect the pancreas?

Answer 13

obstruction of ducts with inspissated secretions leads to dilations, destruction and fibrosis
-exocrine insufficiency/ fat malabsorption

Question 14

How do they diagnose pancreatic exocrine insufficiency?

Answer 14

72 hour fat collection
fecal chymotrypsin or fecal elastase
vitamin ADEK levels

Therapy

• enzyme replacement
• dosing by fat intake, body weight or symptoms

Question 15

CF related diabetes

Answer 15

pancreatic endocrine insufficiency
polyuria, polydipsia, weight loss, unexplained drop in lung function
screen yearly

Question 16

How does CF affect the bones and joints

Answer 16

osteopenia and osteoporosis

• vit D deficiency, calc malabsorption, accelerated bone loss, hypogonadism, inactive, low bmi
• episodic arthritis

Question 17

How does CF affect the GU

Answer 17

female
-endocervicitis, mucus distended cervical glands
-anovulatory
-20% infertile
Males
failure in transport no production 
98% infertile 
-vas deferens missing

Question 18

How does CF affect the sweat glands

Answer 18

pronounced abnormality in Na Cl homeostasis
increased sensitivity to dehydration in hot weather
salty taste to sweat

Question 19

Diagnosis

Answer 19

clinical evidence
lab evidence
-sweat test >60 
-genetic
-nasal potential

Question 20

Therapy

Answer 20

1. airway clearance
2. antibiotics
   -oral
   -nebulized-tobramycin, aztreonam lysine, colistin
   -iv for exacerbation
3. bronchodilators
4. nutrition
   -need 3500-4500 cal/day
   -better weight better outcome
   -tube feeds
5. anti-inflammatories
   -oral steroids
   -inhaled steroids
   -NSAIDs
   -Azithromycin
6. mucolytics
   -rhDNAase
   -hypertonic saline
7. lung transplant
   refer when FEV

Question 21

What is the future therapy for CF?

Answer 21

processing and modulation of CFTR, restoring ion transport
targeted at specific defect
potentiators-ivacaftor --class 3
-bring back lung function!
correctors-lumacaftor--class 2

Question 22

Pros and cons gene therapy

Answer 22

PROS
single defect
only need 5-10% for normal cl transport function
lung accessible
lung normal at birth

Con:

• epithelium is difficult to transfect
• expression is short
• repeat administration not always possible
• CFTR is multi-functional and not all the functions are equally easy to correct