Pathophysiology of cystic fibrosis

Question 1

Cystic fibrosis

Answer 1

• Inherited autosomal recessive disease
• Mutation that occours in ystic fibrosis transmembrane conductance regulator gene
• CFTR involved in the production of sweat, mucus and digestive enzymes
• Ion transportor abnormalities cause dehydrate mucous

Question 2

Long term issues of cystic fibrosis

Answer 2

• Difficulty breathing / coughing up sputum as a result of frequent lung
  infections

Question 3

Other symptoms of cystic fibrosis

Answer 3

• Sinus infections,
• Poor growth
• Fatty stool
• Clubbing of the finger and toes
• Infertility in males

Question 4

Epidemiology of CF

Answer 4

• Most common mutation of delta F508 three base-pair deletion that should code for a phenylalanine
• Diagnosed during childhood mostly caucasian

Question 5

Main signs and symptoms of CF

Answer 5

• salty-tasting skin
• Poor growth and poor weight gain despite normal food intake
• Accumulation of thick, sticky mucus
• frequent chest infections, and coughing or shortness of breath

Question 6

Body systems effected by CF

Answer 6

• Lungs and sinus causing infection and inflammation
• Sweat glands elevated sweat chloride concentration
• Pancreas - Exocrine dysfunction with diabetes

Question 7

Causes of CF

Answer 7

• The CFTR gene found at q31.2 locus of chromosome 7
• Location is 7q31.2 More specifically it is found on the long arm of chromosome 7, region 3, band 1, sub-band 2
• CFTR is a type of gene known as an ABC gene - choride ion channel is the product of the gene

Question 8

Cellular processing of CFTR with cystic fibrosis

Answer 8

• Chloride ions are not transported through the chloride ion channels in CF
• Chloride ions are reduced extracellularly on surface of the epithelium
• Effecting the constituency of mucus
• Na+ and Cl- on airways surface
• Couplled to reduce water flow into aiways of the lumen dehydrates mucus less HCO3 acidifying layer

Question 9

Diagnosis of CF

Answer 9

• Limitations for using DNA testing due to CFTR mutation
• Heel prick test for newborn babies fiind common varients
• Sweat test for chlorine levels >60mM for adults
• Nasal transepithelial potential difference- increased luminal Na+ absorption makes potential more negative in CF patients

Question 10

Management of CF

Answer 10

• Polypharmacy is common
• Stratification of treatment severity
• Maintainance to improve quality of life
• Treat exacerbations aggresively

Question 11

Treatment objectives

Answer 11

• Promote clearance of secreations
• Control lung infection
• Provide accurate nutrition
• Prevent intestinal absorbtion

Question 12

CF causing lung disease

Answer 12

• Mutation of the CFTR gene
• Ion transporter abnomality
• Overly viscous mucus
• Impaired mucous clearance
• Causing an infection can be cleared by antibiotics that could cause tissue damage

Question 13

How can gene therapy in the future effect CF and lung disease

Answer 13

• Looking directly at Mutation of CFTR gene to combat risk of CF

Question 14

Why are mucolytics used?

Answer 14

• Focus on the impaired mucous clearance

Question 15

Three most common
organisms causing lung
infections in CF patients

Answer 15

• Staphylococcus aureus
• Haemophilus influenzae
• Pseudomonas
  aeruginosa

Question 16

Airway surface liquid protects lung

Answer 16

• trap and clear inhaled pathogens
  from the lung via mucociliary transport

Question 17

Periciliary layer and mucus layer

Answer 17

• Grafted brush of tethered
  mucins which are protiens
• Acidity effects mucous consistancy

Question 18

What happens to cilliary clearance in CF

Answer 18

• Becomes ineffective
• Colonised with bacteria
• Chronic inflammations, bronchiectasis and obstruction
  Lower ASL volume

Question 19

Inhaled dornase alf

Answer 19

• DNA forms polymers thickening mucous
• Dornase alfa is a DNAse
• Reduces viscosity of mucous

Question 20

Inhaled hypertonic saline

Answer 20

• Disrupts ionic bonds supporting entanglements
• Disassociates DNA from mucous proteins
• Improved access to endogenous proteolytics

Question 21

Inhaled mannitol

Answer 21

• Hydrates mucous
• Osmotic mechanism

Question 22

ICS used for CF

Answer 22

• Inhaled bronchodialators
• Commonly used for acute relief of obstruction
• No clinical studies on exacerbation
  Other

Question 23

Non medical interventions for CF

Answer 23

• Chest physiotherapy used to aid clearance of mucous from the lungs

Question 24

Treatment for inflammation in CF: Oral corticosteroids

Answer 24

• Reduce rate of decline in lung function
• Reduce frequency of infections
• Unwanted effects preclude long term use

Question 25

CF and its effects on GI disease: Pancreatic enzyme supplements

Answer 25

• Supplements contain protease, lipase and amylase
• Inactivated by stomach acid

Question 26

CF and its effects on GI disease: Diet

Answer 26

• High calorie diet needed as digestion compromised