Cystic Fibrosis Flashcards
What is cystic fibrosis?
CF is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, on chromosome 7.
There are at least 2,000 mutations in the CFTR gene. Different mutations result in different phenotypes. Some mutations result in milder forms of the disease
The most common mutation in Caucasians is the delta-F508 (DF508).
What is CFTR?
CFTR is an ATP-responsive chloride channel that also affects other cellular activities, such as sodium transport across the respiratory epithelium, composition of cell surface glycoprotein and antibacterial defences.
What causes high sodium sweat in CF?
Primary secretion of sweat duct is normal but CFTR does not absorb chloride ions, which remain in the lumen and prevent sodium absorption.
What causes pancreatic insufficiency in CF?
Production of pancreatic enzymes is normal but defects in ion transport produce relative dehydration of pancreatic secretions, causing their stagnation in the pancreatic ducts.
What causes biliary disease in CF?
Defective ion transfer across the bile duct causes reduced movement of water in the lumen so that bile becomes concentrated, causing plugging and local damage.
What causes GI disease in CF?
Low-volume secretions of increased viscosity, changes in fluid movement across both the small and large intestine and dehydrated biliary and pancreatic secretions cause intraluminal water deficiency.
What causes respiratory disease in CF?
Dehydration of the airway surfaces reduces mucociliary clearance and favours bacterial colonisation; local bacterial defences are impaired by local salt concentrations and bacterial adherence is increased by changes in cell surface glycoproteins.
Increased bacterial colonisation and reduced clearance produce inflammatory lung damage due to an exuberant neutrophilic response involving mediators such as IL8 and neutrophil elastase.
Presentation of CF
As normal digestive function is possible with <5% pancreatic function, CF can present at any age.
The most common presentation is with respiratory problems - usually recurrent lower respiratory tract infection (LRTI) with chronic sputum production.
However, immunoreactive trypsinogen (IRT) is now measured on a dried blood spot obtained on the Guthrie card at day six of life. Samples with abnormally raised IRT levels will undergo CFTR mutation screening.
Pseudo-Bartter’s syndrome in infancy. Also acute pancreatitis, rectal prolapse and portal HTN.
Family history, screening and respiratory diseases are usually ways of diagnosis.
Male infertility.
Signs of CF includes finger clubbing, cough with purulent sputum, crackles, wheezes and FEV1 showing obstruction.
Investigations for CF
Sweat testing confirms the diagnosis and is 98% sensitive. Chloride concentration >60 mmol/L with sodium concentration lower than that of chloride on two separate occasions.
Molecular genetic testing for CFTR gene.
Sinus X-ray or CT scan - opacification of the sinuses is present in almost all patients with CF.
CXR or CT of thorax.
Lung function testing - spirometry is unreliable before 6 years.
Sputum microbiology - common pathogens include Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, Escherichia coli and Klebsiella pneumoniae.
Various blood tests including FBC, U&Es, fasting glucose, LFTs and vitamin A, D and E levels are usually performed.
Semen analysis if appropriate.
Management of respiratory disease in CF
Most of the morbidity and mortality associated with CF is caused by respiratory disease where chronic infection and inflammation lead to bronchiectasis, progressive airflow obstruction, cor pulmonale and finally death.
In the early, pre-infected stages, mucus clearance, preventing infection and maintaining good lung function are the main aims.
Chest physiotherapy should be given twice-daily and this is increased with infective exacerbations.
Additional physical exercise is also beneficial and should be encouraged.
Regular sputum samples are sent for bacterial culture.
Prophylactic antibiotics are used to reduce S. aureus in children and also to prevent secondary bacterial infections when a patient has a presumed acute viral respiratory infection.
Antibiotic choice for infective exacerbations will depend on the organism.
Infection with less common organisms requires specialist microbiological advice.
Management of pancreatic insufficiency in CF
At least 85% of patients with CF have pancreatic insufficiency.
This usually presents with neonatal meconium ileus or failure to thrive, steatorrhoea and malnutrition which can cause anaemia, vitamin deficiency and sometimes oedema. It can cause rectal prolapse, intussusception, volvulus and obstruction.
Pancreatic insufficiency should be confirmed with stool elastase; presence of unsplit fat globules in stool or 2-3 days’ stool collection for faecal fat.
Pancreatic enzymes are traditionally prescribed.
Patients should be weighed regularly. They will have high energy needs, especially those with recurrent chest infections or those who lose a lot of fat in their stools. Protein intake needs to be at least twice the normal recommended amounts.
If the patient is unable to maintain weight, enteral feeding via gastrostomy may be required.
Management of liver disease in CF
Liver disease is seen in up to 30% of patients by adulthood. Liver cell failure usually occurs late, with ominous prognosis. It is fatal in 2-4% of CF cases and is the third most common cause of death in CF patients.
Ultrasound is a useful confirmatory investigation. Other imaging modes - eg, scintigraphy - may be required.
Ursodeoxycholic acid improves bile flow and produces some improvement but does not alter the course of chronic liver disease.
Liver transplantation should be offered to CF patients with progressive liver failure and/or with life-threatening sequelae of portal hypertension. They should also have relatively good lung function, to support long-term survival.
Management of other conditions in CF
Nearly all males with CF have obstructive azoospermia with sexual function that is otherwise normal; there is normal spermatogenesis but no vas deferens. Early counselling should be offered about infertility and sperm count. In vitro fertilisation with aspirated sperm has been used successfully.
Women are generally of normal fertility but need genetic counselling. There is an inherent risk to pregnancy with severe lung disease (FEV1 <30% predicted).
Increased risk of osteoporosis. Patients should be recommended to take calcium, vitamin D and bisphosphonates as appropriate. Patients usually have regular dual-energy X-ray absorptiometry (DXA) scans.
Follow up in CF patients
UK standards recommend that:
o Patients should be seen twice a year by a multidisciplinary team working in a specialist centre.
o GPs should provide shared care in conjunction with specialists.
o Children should be transferred to adult services by the age of 18 at the latest.
In general, the following investigations are performed at regular intervals:
o Pulmonary function tests.
o CXR.
o DXA scan.
o Blood glucose.
o Respiratory cultures.
o Ultrasound scan of the liver.
o Vitamin D levels.
• All patients should receive the annual influenza vaccination. They should also receive the pneumococcal vaccine.
What is a cough?
Cough is a reflex response to airway irritation. It is triggered by stimulation of airway cough receptors, either by irritants or by conditions that cause airway distortion.
