Notes by Harriet Wood

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Cystic Fibrosis Genetics

Autosomal recessive.

Gene located on chromosome 7 - Codes for protein called cystic fibrosis transmembrane

regulator (CFTR) – mutated in CF. - CFTR is a cyclic AMP-dependant chloride channel

blocker.

>800 different gene mutations cause CF – Commonest is ΔF508 mutation (78% cases).

Patho-physiology

Abnormal ion transport across epithelial cells of exocrine glands in respiratory tract and pancreas

- ↓ Cl- excreted into airway lumen, ↑ Na+ absorption, water follows = ↑ viscosity of secretions.

Abnormal function of sweat glands = ↑ conc. of Na+ and Cl- in sweat (80-125mmol/L in CF, 10-14mmol/L normal).

CFTR also affects inflammatory processes and defence against infection.

Signs and Symptoms

Infancy

Meconium ileus (10%) neonatal period - Thickened meconium causes IO with vomiting, abdo

distention and failure to pass meconium in first few days of life.

Prolonged neonatal jaundice.

Failure to thrive.

Recurrent chest infections - Viscid mucus in smaller airways predisposes to c.i. - Organisms: Staph aureus, Haemophilus influenzae, Strep

pneumoniae, Pseudomonas aeruginosa - Leads to damage of bronchi wall, bronchiectasis and

abscess formation.. - Symptoms: Persistent, loss cough productive of purulent

sputum. - Signs: Hyperinflation, coarse crepitations or expiratory

rub, ± finger clubbing.

Malabsorption and steatorrhoea - Due to insufficiency of the pancreatic exocrine enzymes

(lipase, amylase, proteases). - Pass large, pale, offensive, greasy stools throughout day.

Carrier rate 1/25. 1/2500 births. Commonest ethnic group:

Caucasians

Notes by Harriet Wood

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Young Child

Bronchiectasis (chronic dilation of bronchi)

Rectal prolapse

Nasal polyp

Sinusitis

Older Child, Adolescent, Adult

DM (either IDDM or NIDDM).

Cirrhosis and portal hypertension.

Distal intestinal obstruction - Viscid mucofaeculent material obstructs bowel.

Pneumothorax/ recurrent haemoptysis (cough up blood).

Persistent Pseudomonas infection - Some also have Burkholderia cepacia which markedly ↓

lung function - spread is from person to so CF patients are advise not to socialise with other CF sufferers.

Aspergillosis. Male infertility

- Due to abnormalities of vas deferens.

Women have ↓ fertility - Caution that their breast milk has a high Na+

concentration.

↑ psychological problems.

Diagnosis

Sweat test - Stimulated by pulocarpine iontophoresis - collected into a

capillary tube or absorbed onto a weighed piece of filter paper.

- Diagnostic error if inadequate volume of sweat – do two tests to confirm results.

- Sweat Cl- >60mmol/L = CF (<40 is normal).

CXR - Hyperexpansion, peribronchial shadowing, bronchial wall

thickening, ring shadows.

Also: IRT/DNA, malabsorption screen, glucose tolerance test, lung function tests, sputum culture.

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Screening

Newborn infants: - Immunoreactive trypsin (IRT) is ↑ in CF patients – can

be measure in blood taken for biochemical screening of all babies (Guthrie test) – not routinely done in UK.

- To confirm do sweat test and counsel parents. - Early identification allows early nutritional management,

introduction of prophylactic antibiotics, prompt recognition and treatment of respiratory infections

- Enables genetic counselling for parents as ¼ risk of recurrence and possibility of prenatal diagnosis in future pregnancies.

Antenatal carrier-status testing is possible.

Pre-implantation analysis after IVF at 8 cell stage (one cell removed and analysed – only embryos without CF reimplanted.

Management

Multidisciplinary approach:

Paediatricians, physiotherapists, dieticians, nurses, primary care team, teachers, parents, child.

Respiratory management:

Physiotherapy bd/tds (depending on amount of sputum they produce).

- Parents taught chest percussion and postural drainage. - Older patients learn forced expiration techniques.

Physical exercise encouraged - Strengthens chest muscles and avoids reaccumulation of

secretions.

Persistent bacterial chest infections are a problem: - Continuous oral antibiotics. - IV therapy for acute exacerbations (central venous

catheter with s.c. port of access often implanted so can give iv at home).

- Nebulised antibiotics if Pseudomonas.

Some have reversible airway obstruction – give bronchodilators or inhaled steroids.

Nutritional management

Treat pancreatic insufficiency: - Oral enteric-coated pancreatic supplements (Pancrex V)

with all meals and snacks.

Omeprazole helps absorption by ↑ duodenal pH.

Aims of therapy:

‘To prevent progression of the lung disease and to maintain adequate nutrition and growth’.

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High-calorie diet - To compensate for malabsorption - Because energy requirement in CF children is 30-40%

above normal - Can overnight feed via a gastrostomy.

Fat-soluble vitamin supplements (A, D, E, K). Miscellaneous

Ensure full vaccinations.

Psychological and emotional support.

Genetic counselling.

Possibilities

Heart-lung transplantations.

Gene therapy currently being assessed.

Prognosis

Median survival is >30 years. Death from pneumonia or cor pulmonale.

Complications

Haemoptysis Pneumonia Pneumothorax Pulmonary osteo-arthropathy DM Cirrhosis Cholesterol gallstones Fibrosing colonopathy Male infertility

Important Note These notes were written by Harriet Wood, as a fourth year medical student in 2009. They are presented in good faith and every effort has been taken to ensure their accuracy. Nevertheless, medical practice changes over time and it is always important to check the information with your clinical teachers and with other reliable sources. Disclaimer: no responsibility can be taken by either the author or publisher for any loss, damage or injury occasioned to any person acting or refraining from action as a result of this information. Please give feedback on this document and report any inaccuracies to: support@askdoctorclarke.com