Raymond (Cystic Fibrosis) Flashcards
What is cystic fibrosis?
An inherited genetic disorder. Defective CFTR gene (cystic fibrosis transmembrane conductance regulator) on chromosome 7 which controls the transport of Na+ and Cl-. It is an autosomal recessive disorder meaning it is on a numbered chromosome not a sex chromosome and you can be carrier for the mutated gene and not present with CF. Most common mutation is the delta-F508.
Epidemiology of CF
1 in 2,500 babies are born with CF in UK
10,655 people are living with CF as of 2019 in UK
1 in 25 people of caucasian descent are carriers of the CF gene
Affects around 100,000 people worldwide
Family history of CF
CF is a genetic condition. It is an autosomal recessive disease caused by inheriting two copies of the faulty gene. If two carriers have a baby the child has 1 in 4 change of having CF
Pathophysiology of CF
CFTR channel is an ATP-responsive chloride channel. It is found all over the body on the surface of epithelial cells- sweat glands, lung, pancreatic duct and GI tract. Defects mean Cl- ions unable to cross the membrane. Shift in electrolytes means water is absorbed from the epithelial surface and therefore mucus is more viscous in the airways. Mucus stasis leads to repeat infections and inflammation in airways
6 functional mutation classes of CF
Class 1 is the works and gets less severe going down to 6
Class 1- CFTR not synthesised
Class 2- CFTR is synthesised in an abnormal form which can leave the endoplasmic reticulum
Class 3- CFTR is synthesised but there are problems with its activation and regulation within the cell
Class 4- CFTR reaches the surface but chloride transport is defective
Class 5- CFTR synthesis or processing is partly defective
Class 6- CFTR is synthesised but there is defective conductance of other ion other than chloride
Prognosis of CF
In 2019 median age of CF was 21 yrs old. The median predicted survival age now is 49.1 yrs old. Females and those from lower socio-economic classes have a worse prognosis. CF accounts for 114 deaths in the UK in 2019.
We cannot cure it so we treat symptoms to improve quality of life.
Diagnosis of CF
- Newborn screening- heel price blood test to detect immunoreactive trypsinogen. Trypsinogen is predicted in the pancreas. Patients with CF have more trypsinogen in the blood (not supposed to be in the blood)
- Sweat test- easiest and most common test performed. Take a sweat swab and test it. Patient with CF have more Na+ and Cl- in their swear
- Genetic test- test for the defective gene
Sweat gland
Sweat is secreted as an isotonic solution of water and sodium chloride. As sweat passes along the duct NaCl is absorbed into the reabsorptive duct cells. CFTR channel transports Cl-. Na+ channel transports Na+. Produces hypotonic bead of sweat. In CF Cl- are not reabsorbed from sweat. To balance the electrical charges Na+ reabsorption is prevented. Produces hypertonic sweat.
Complications of CF in the lungs
Our lungs are covered with a moist film called the airway surface liquid (ASL). The ASL is a salt containing mucus gel layer that traps bacteria and foreign particles breathed in. Cilia on the surface of the lung cells sweep the particles out of the lungs to the mouth. This mucociliary clearance (MCC) is an important defence mechanism against infections. As the mucus is not cleared in a CF patient the pathogens/infections build up.
Why does the mucus become think in a patient with CF?
Decreased Cl- transport
Excess Na+ reabsorption from the ASL
Water follows Na+
Water flows out os the ASL
ASL becomes thick and dehydrated
Bacterial complications in lungs (CF)
Mucus raps bacteria. Mucus is a good environment for bacteria to thrive in. Common organisms: Pseudomonas aeruginosa (leads to pneumonia) and Staphylococcus aureus (responsible for skin infections). Causes inflammation and scarring which leads to lung damage. The end result is bronchiectasis (widening of bronchioles), COPD, cor pulmole (hypertrophy of right ventricle). Repeating the same treatment for each infection can lead to resistant strains of bacteria.
Lung management in CF
- Mucus clearance with chest physiotherapy (chest exercises to clear mucus both physically and mechanically)
- increased in times of exacerbations
- Mucus modifying drugs- recombinant human dornase alfa (pulmozyme)- breaks down DNA in mucus to make it less viscous
- Vibrating vest- loosens mucus then clear after
- Regular sputum samples for culture- every 3 months to assess presence of infection
- Bronchodilators
- Transplant
- Gene therapy e.g. Ivacaftor- produces gene to make the CFTR protein
- Eradication regimes
- oral, IV, and inhaled abs
- Prophylactic Abx- benefits vs risk- builds resistance, may need abx in future but not giving now could harm patient
How does CF affect pancreatic ducts?
Bile ducts and pancreatic ducts lead to intestine. Bile ducts go from liver to stomach. They contain mucus which is too thick in CF patients. Trypsinogen and bile get stuck in pancreatic and bile ducts.
How does CF affect GI function?
Reduced pancreatic recreations reduces fat absorption leading to steatorrhoea (more fat excreted in stools)
Viscous secretion in the intestinal tract can lead to intestinal obstruction syndrome (can lead to blockages, changes in BP)
Pancreatic damage can lead to diabetes as body may not produce enough insulin
Symptoms of CF
Hypertonic sweat
Production of thick, viscous sputum
Cough
Shortness of breath
Recurring chest infections
Pancreatic insufficiency
Nutrient malabsorption- fat soluble vitamins e.g. A, D, E, K
Malnutrition
Constipation
Bloating
Pancreatitis
Food not digested properly
Obstruction of liver bile duct
Gall stones
Intestinal obstruction
Infertility
