Cystic Fibrosis Flashcards
What is CF
Cystic fibrosis (CF) is an inherited, autosomal recessive, multi-system disease affecting mucus glands.
Respiratory problems most prominent, as well as pancreatic insufficiency.
Epidemiology of CF
Cystic fibrosis is the most common inherited condition in the Caucasian population, affecting 1/2500 births, whilst 1/25 of the population are carriers
RFs of CF
- Family history of cystic fibrosis
- Known parental carriers: if both parents are known carriers, the child has a 1 in 4 chance of having cystic fibrosis
- Caucasian ethnicity
What is CF due to?
mutations in the CF transmembrane conductance regulator (CFTR) on chromosome 7
Most common CF mutation?
Δ-F508 is the most common mutation, where the codon for phenylalanine (F) in the CFTR gene is deleted, resulting in proteolytic degradation.
What is the CFTR protein?
channel protein that pumps chloride ions into various secretions, those chloride ions help draw water into the secretions, which ends up thinning them out.
Pathophysiology of CFTR protein with ∆F508 mutation
- CFTR Protein gets misfolded and can’t migrate from the endoplasmic reticulum to the cell membrane
- meaning there’s a lack of CFTR protein on the epithelial surface, and this means that it can’t pump chloride ions out
- means water doesn’t get drawn in, and the secretions are left overly thick.
Respiratory effects of CF
- Dry airways and impaired mucociliary clearance: results in cough, dyspnoea and recurrent pneumonia
- Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections,
- Bronchiectasis
- Resp failure
What bacteria cause infiltrate?
- Pseudomonas aeruginosa
- Staphylococcus aureus
- Haemophilus influenza
- Klebsiella pneumoniae
- Escherichia coli
- Burkholderia cepacia
- Aspergillus
GI effects of CF
Thickened secretions within small and large bowel: presents with failure to pass meconium (stool) and can cause bowel obstruction
Pancreatic effects of CF
- Thick pancreatic and biliary secretions that cause blockage of the ducts, result in a lack of digestive enzymes such as pancreatic lipase in the digestive tract - results in malabsorption.
- Pancreatitis may develop as the pancreas gets damaged, because backed-up digestive enzymes degrade the cells lining the pancreatic ducts
- Destruction of pancreatic tissue can also compromise the endocrine function of the pancreas, causing insulin-dependent diabetes.
Liver cirrhosis and Right HF due to CF
Thickened biliary secretions: may block the bile ducts resulting in liver fibrosis, cirrhosis and portal hypertension
HF: Occurs due to pulmonary hypertension, resulting in cor pulmonale
Other issues of CF
- Congenital bilateral absence of the vas deferens in males: patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate, resulting in male infertility
- Females able to conceive but often develop secondary amenorrhea (absence of menstruation) as disease progresses
Signs of CF
- Low weight or height on growth charts
- Nasal polyps
- Finger clubbing
- Crackles and wheezes on auscultation
- Abdominal distention
Symptoms of CF
-
Chronic cough
- Can be haemoptysis if inflammation erodes into a blood vessel
- Thick sputum production
- Recurrent respiratory tract infections
- Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
- Abdominal pain and bloating
- Parents may report the child tastes particularlysaltywhen they kiss them, due to the concentrated salt in the sweat
- Poor weight and height gain (failure to thrive)
