Cystic fibrosis

 

 

Aetiology

Autosomal recessive

1 in 2 500 – 3 300 live births

1 in 19 carry the gene in heterozygous form

70% of cases caused by the F508 mutation on the long arm of chromosome 7

Cystic fibrosis transmembrane regulator (CFTR) gene

Abnormal regulation of sodium and chloride channels

Chloride movement seems most important in aetiology

700 other mutations account for 30% of cases

 

Screening

Carrier screening is available

 

 

Pathophysiology

Exocrine gland dysfunction

Excessive sodium chloride secretion by sweat glands

Blockages caused by secretion accumulation

Increased viscosity of pancreatic and lung secretions

 

Pancreas

Viscid mucous plugs in the pancreatic ducts cause atrophy and secondary fibrosis of the pancreas

Failure of pancreatic secretions

 

Lungs

Respiratory sputum is viscid and difficult to cough up

Patchy areas of bronchial obstruction

Stasis – infection

Anterior-posterior diameter of chest increased

Widespread emphysema

Reduced air entry

Expiration prolonged

Crepitations

Possible bronchospasm

Small areas of consolidation due to bronchopneumonia

Diffuse bronchiectasis – chronic dilation and destruction of the bronchial walls

Eventual cor pulmonale

 

Biliary

Bile ducts may become plugged by viscous secretions of bile

Biliary cirrhosis

Portal hypertension

 

Saliva

Thicker and more viscous than normal

 

 

Diagnosis

NaCl in sweat is 2 – 5 times higher than normal

Sodium concentrations of more than 60 mmol / litter in sweat

Test may be repeated several times if uncertain

Duodenal secretions will show reduced or absent pancreatic secretions

 

 

Clinical features

 

 

Meconium ileus

A form of intestinal obstruction in the newborn

Causes by a viscous meconium plug in the small bowel

Caused by the absence of trypsin which normally digests and softens the meconium

 

 

Meconium ileus equivalent

Occurs in children of all ages

Gumlike masses in the caecum can obstruct the bowel causing nausea, vomiting and pain

 

 

Steatorrhoea

90% of sufferers have a malabsorption syndrome

Caused by lack of pancreatic secretions

Bulky, pale, greasy, foul smelling stools several times daily

Progressive wasting

Appetite may be increased

Prolapse of the rectum occurs in 25% of patients, usually in the first 3 years of life

 

 

Respiratory disease

Frequent coughing

Cyanosis

Dyspnoea

Finger clubbing

Recurrent respiratory infections

Infections may begin in early infancy or later at 2 – 3 years

Blood streaking in mucus usually indicates infection

Pneumothorax may occur in advanced disease

Progressive disability due to respiratory insufficiency

 

Mouth

May be dry with predisposition to infections

 

Other features

Retarded growth

Delayed puberty

Ongoing partial intestinal obstruction due to tenacious faeces

Diabetes mellitus may develop from pancreatic fibrosis

 

 

Prognosis

Depends very much on treatment

There is a variation in level of severity

Death may occur from GI obstruction shortly after birth

 

 

Reproduction

98% of males are sterile due to blockage of the vas deferens

Women have sub-fertility due to thick cervical secretions

 

 

Treatments

 

 

Respiratory

Prompt and aggressive treatment of infections

Intravenous and aerosolised antibiotics

Staphylococcus aureus and H. influenze Pseudomonas aeruginosa are common organisms

Physiotherapy, postural drainage and percussion to increase expectoration

Aerosols of mucolytics – recombinant human deoxyribonuclease (DNase)

Humidified oxygen during acute episodes

Note - many of these children retain CO2

Daily ibuprofen slows rate of decline in pulmonary function

Do not nurse two together

Transplantations

 

Pancreas

Pancreatin, powdered or in tablets or capsules - Titrated dose

Reduced appetite is often a sign of improved digestion

Well balanced high protein, high calorie – but possibly reduced fat

150% of RDA is often needed for normal growth

Vitamin supplements may be needed

Treat constipation and obstruction with osmotic and other laxatives

Prevent constipation / obstruction with a stool softener, bulky diet and mild stimulant

 

Give adequate salt to prevent hypochloraemic and hyponatraemic alkalosis

Plenty of salt in hot weather or when febrile

 

Cystic fibrosis society and local groups