Respiratory: Cystic Fibrosis Flashcards
What type of inheritance pattern does CF have?
Autosomal recessive
Which gene is defective?
The CF transmembrane conductance regulator gene (CFTR) = a cyclic AMP dependent chloride channel found in the membrane of cells
The gene for CFTR is located on chromosome..
7
What is the most frequent mutation of the CFTR gene?
DeltaF508 (this protein is misfolded and cannot migrate from the endoplasmic reticulum to the cell membrane - lack of CFTR on epithelial surface) A class II mutation
CF is the most common life limiting autosomal recessive condition in Caucasians. True or false?
True
What is the incidence rate?
1 in 2500 live births
Carrier rate of 1 in 25
What is the life expectancy for current newborns?
Into the 40s
Describe the pathophysiology
Abnormal ion transport occurs across epithelial cells, causing increased viscosity of secretions.
The CTFR channel protein pumps chloride ions into secretions. The chloride ions help draw water into the secretions, thinning them out.
Is CF a multi system disorder?
Yes
How are newborns affected?
In the intestines, thick viscous meconium is produced leading to meconium ileus in 10-20% of infants
How can the pancreas be affected?
The pancreatic ducts become blocked by thick secretions, leading to pancreatic enzyme insufficiency and malabsorption
Without pancreatic enzymes, what is not absorbed?
Protein and fat
What can fat malabsorption lead to?
Steatorrhoea (fat containing stools)
Why can the pancreas become damaged?
The trapped enzymes degrade the cells that line the ducts - local inflammation and acute pancreatitis. With repeated episodes = chronic pancreatitis with development of cysts and fibrosis
Pancreatic damage can cause endocrine dysfunction and lead to…
Insulin dependent diabetes
Why do recurrent chest infections occur?
The thickened mucus in the airways impairs ciliary function. Consequently there is retention of mucopurulent secretions - this facilitates bacterial overgrowth
What bacteria typically cause the chest infections?
Staphylococcus aureus
Haemophilius influenzae
Pseudomonas aeruginosa
Burkholderia cepacia
What respiratory signs and symptoms can occur?
Persistent wet cough
Purulent sputum production
Hyperinflation of chest due to air trapping
Coarse inspiratory crepitations and/or expiratory wheeze
With established disease: finger clubbing
Chronic lung infections can lead to…
Damage to bronchial wall, bronchiectasis, abscess formation
What is the leading cause of death with CF?
Respiratory failure
What is bronchiectasis?
Airway wall damage causing permanent dilation of the bronchi
Over what percentage of children with CF have pancreatic exocrine insufficiency? (Lipase, amylase, proteases)
90%
Pancreatic exocrine insufficiency leads to…
Maldigestion and malabsorption. Untreated this leads to faltering growth
How can pancreatic insufficiency be diagnosed?
Demonstrating low faecal elastase
Faecal elastase is not degraded after secretion - a way to measure pancreas’ exocrine function
Why is there infertility in men?
They lack the vas deferens - carries sperm from testes to urthera in penis
Other than recurrent chest infections, what other respiratory conditions can occur?
Bronchiectasis Nasal polyps Sinusitis Allergic bronchopulmonary aspergillosis (ABPA) Pneumothorax
What is allergic bronchopulmonary aspergillosis?
A hypersensitivity reaction to aspergillus fumigatus - growth within a sinus or lung cavity provokes an IgE mediated response, causing airway inflammation, bronchospasm, bronchiectasis
About 10-20% of infants with CF present in neonatal period with meconium ileus causing intestinal obstruction. Typically this presents as…
Vomiting
Abdominal distension
Failure to pass meconium in first few days of life
How is meconium ileus treated?
Usually surgery
Gastrografin enema may relive obstruction
How is the meconium usually passed in the stools?
Usually at birth the meconium (made up of bile, mucus, amniotic fluid, water) is broken down by pancreatic enzymes and is passed in the stools.
What features of CF are typically seen as a newborn?
Meconium ileus
Neonatal jaundice
What features are seen in infancy?
Growth faltering
Recurrent chest infections
Malabsorption, steatorrhoea
What features are seen in young children?
Bronchiectasis
Rectal prolapse
Nasal polyps
Sinusitis
What features are seen in older children?
ABPA DM Cirrhosis and portal hypertension Distal intestinal obstruction Pneumothorax or recurrent haemoptysis Sterility in males
Is there a screening test?
Yes, all newborn infants in UK screened for CF
Reduces diagnostic delay
How is screening done?
Heel prick test - immunoreactive trypsinogen (IRT) raised in newborn infants with CF
Samples with raised IRF are screened for common CF gene mutations and infants with 2 mutations have a sweat test to confirm diagnosis
How is CF diagnosis confirmed?
Sweat test - to confirm the concentration of chloride in sweat (it is markedly elevated: 60-125mmol/L in CF, in normal children = 10-40)
Diagnostic errors in the sweat test are common if…
There is an inadequate volume of sweat collected
What is involved in the sweat test?
Sweating stimulated by applying low current to pilocarpine applied to skin - sweat collected into capillary tube or absorbed onto filter paper. Concentration of sodium and chloride measured - it is the chloride that is important for diagnosis
Why is chloride raised in the sweat test in those with CF?
The defective / absent CFTR protein does not reabsorb chloride into the sweat duct - remains on the skin surface
What is another term for the IRT test?
Guthrie test
What other test, not performed for diagnosis, are likely to be abnormal?
Raised GGT
Vitamins A,D,E,K low (fat soluble) - lost in steatorrhoea
CXR - hyperinflation, bronchiectasis
Abdominal USS - fatty liver, cirrhosis, chronic pancreatitis
Spirometry - obstructive pattern
What is the aim of therapy?
Prevent progression of lung disease
Maintain adequate nutrition and growth
The effective management of CF requires a …
MDT approach
At least annual review in a specialist centre
Describe respiratory management
From diagnosis: physiotherapy at least twice per day, aiming to clear airways and secretions
In younger children, parents taught to perform airway clearance at home using chest percussion and postural drainage
Older patients - controlled deep breathing exercises
Physical exercise beneficial and encouraged
Many CF specialists recommend continuous prophylactic oral antibiotics (usually flucloxacillin) with additional rescue antibiotics for increase in symptoms
Persisting symptoms: IV therapy to limit lung damage - usually 14 days via PIC
Chronic pseudomonas infection is associated with a more rapid decline in lung function, which is slowed by daily use of …
Nebulised antipseudomonal antibiotics
What can be used to help decrease the viscosity of respiratory secretions?
Nebulised DNase or hypertonic saline
If venous access becomes difficult, what can be done?
Implantation of central venous catheter with a port
What is the only therapeutic option for end stage CF lung disease?
Bilateral sequential lung transplantation - over 50% survival at 10 years
Describe the nutritional management
Dietary status assessed regularly
Oral pancreatic enzyme supplements taken with all meals and snacks
High calorie diet including high fat intake
Dietary intake recommended at 150% normal - overnight feeding via gastrostomy may be needed
Fat soluble vitamin supplements
What can be used to treat CF patients who are homozygous for the delay F508 mutation and how does it work?
Lumicaftor - a CFTR corrector
Partially restore CFTR numbers - increasing numbers of the protein transported to cell surface
What is ivacaftor?
A CFTR potentiator - increases they probability that the defective channel will be open and allow chloride ions to pass through the channel
What percentage of adolescents with have evidence of liver disease, with hepatomegaly on palpation, abnormal LFTs and abnormal USS ?
Up to 1/3
What can be given to help improve bile flow?
Ursodeoxycholic acid
Is it rare for the liver disease to progress to cirrhosis, portal hypertension and liver failure?
Yes
But liver transplant is generally very successful in CF related liver failure
If viscous material obstructs the bowel, how can it be cleared?
A combination of oral laxative agents
Why is it advised that patients with CF should minimise contact with each other?
To prevent cross infection with virulent strains of pseudomonas aeruginosa and Burkholderia cepacia causing rapid decline in lung function
In younger patients, respiratory monitoring is based on..
Symptoms
Older children should have their lung function measured regularly by…
Spirometry
The FEV1 is an indicator for clinical severity
