Cystic Fibrosis Flashcards

1
Q

What is the genetics underpinning CF?

A

Autosomal Recessive Disorder
CFRT gene (codes for CFTR protein) mutation on long arm of chromosome 7.

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2
Q

What is the role of the CFTR protein?

A

Is a protein channel - transported to cell membrane
Typically found on epithelial cells
CFTR - transported chloride ions out of cell - encourages movement of water molecules out down a concentration gradient
Ensures thin/hydrated mucus layer.

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3
Q

What happens when the CFTR gene is mutated?

A

Often delF508 mutation, typically comes during CFTR folding.
Malfunctioning protein is not transported or inserted into the channel membrane
Unable to transport chloride ions out, loss of subsequent movement of water ions across epithelial cells onto the epithelial cell surface.
Results in thick, dehydrated mucus on epithelial surface.

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4
Q

How common is the CFRT mutated allele?

A

1 in 25 people in the UK are carriers of the CF mutated allele

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5
Q

Describe the changes in the airway of a person with CF?
Why is this problematic?

A

Thickening of the bronchial walls
Thick layer of dehydrated mucus
Cilia struggle to brush mucus away.
PAthogens become trapped in mucus lining the airways
Not removed by mucociliary escalator - able to proliferate and cause recurrent infection leading to inflammation
Leads to damaged cell wall and further increased mucus production

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6
Q

What is a common respiratory complication of Cystic Fibrosis?

A

Bronchiectasis

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7
Q

How is cystic fibrosis diagnosed?

A

All newborn babies are screened for CF as part of newborn blood spot test (heel prick test). If suggests CF then undergo:
Sweat test (98% sensitive) - chloride concentration >60mmol/L with sodium conc lower than that of chloride on two separate occasions
Genet test - blood or saliva checked for faulty gene
Aminocentesis/chronic villus sampling can also be done during the antenatal period.

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8
Q

How might CF present in the perinatal period?

A

Bowel obstruction with meconium ileus (thickeing of meconium)
Haemorrhagic disease of the newborn (malabsorption - lack of Vit K)
Prolonged jaundice (obstructive jaundice CFTR for lining of biliary tree)

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9
Q

How might CF present in infancy and childhood?

A

Recurrent respiratory infections
Chronic pulmonary disease
Diarrhoea
Failure to thrive
Rectal prolapse
Nasal polyps
Acute pancreatitis
Portal hypertension and variceal haemorrhage
Hypoproteaenima and odema

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10
Q

How does cystic fibrosis present in adolescene/adulthood?

A

Recurrent respiratory tract infections
Atypical asthma
Bronchiectasis
Chronic Pulmonary disease
Chronic sinus disease
Male infertility (congential bilateral absence of the vas deferens)

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11
Q

How is cystic fibrosis a multisystem disease?

A

CFTR protein found in
Lungs (leading cause of mortality), GIT (often present first including the pancreas and biliary system), Urogenital (problems in adulthood)

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12
Q

How does cystic fibrosis affect the digestive system?

A

Meconium ileus - thick mucus in meconium = BO
Blocked bile ducts = poor fat absorption, liver damage
Blocked pancreatic duct = poor digestion (protein &fat), pancreatitis and diabetes.
Intestinal obstruction/intussuception
Abdominal distention

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13
Q

What is the affect of CF in the respiratory system?

A

Abnormal CFTR protein - Cl-/HCO3- not transported out onto epithelial surface, water does not follow.
Thick mucus and mucociliary dysfuncation = chronic infections, inflammation (perpetuated by proteases and cytokines) -> airway destruction
Blocked airways
Symptoms = chronic cough, wheezing, recurrent pneumonia.

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14
Q

What are the affects of cystic fibrosis in the urogenital system?

A

Infertility in men - absence of vans deferens
Decreased fertility in women (thicker cervical mucus and ovulation issues due to poor nutrition)

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15
Q

How is disease progression in cystic fibrosis monitored?

A

Chest radiographs (most common)
Pulmonary function tests (obstructive spirometry)
Arterial blood gas analysis

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16
Q

Interpret this CXR: 13F, chronic cough.

A

Tram tracks and ring markings - indicative of cystic bronchiectasis
Hyperinflation of the chest.

17
Q

What are the physical signs of CF that may be seen on examination?

A

Finger clubbing
Wheezes (upper lobes)
FEV1 = obstruction
Crackles
Cough with purulent sputum.

18
Q

What are some potential complications of cystic fibrosis?

A

Osteoporosis - lack of Vitamin D
Diabetes
Nasal polyps and sinus infection
Bronchiectasis
Pneumothorax
GI problems - DIOS
Cor pulmonale
Fertility problems
Liver disease/failure - cirrhosis
Kideny problems
Allergic bronchopulmonary aspergillos
Pancreatitis
Malnutrition.

19
Q

What is the prognosis with cystic fibrosis?

A

No cure
50% survive over the age of 40yrs.

20
Q

What is the conservative management of cystic fibrosis?

A

Chest physio - postural drainage
Physical exercise
Dietary and nutritional advice - high calorie, high protein, high in salt, high calcium.
Patient education
Vaccinations
Annual screening for complications - includes PFT, bone scan,

21
Q

What medical treatment can be given for cystic fibrosis?

A

Carbocisteine - decrease sputum viscotiy (mucolytic)
Anitbiotics
Hypotonic saline (maintenance fluid in acute infections)
Bronchodilators
Steroids - treat nasal polyps
Insulin - treat diabetes
Creon - pancreatic insufficiency (digestive enzymes lipase, protease, amylase)
Biological therapies (Ivacaftor)

22
Q

What surgical treatment can be used for cystic fibrosis?

A

Lung transplant

23
Q

What are the typical symptoms of cystic fibrosis?

A

Fatigue
Chronic cough
Recurrent URI
Thick, sticky mucus
Chronic hypoxia: clubbing, barrel chest
Reduced absorption of vitamins and enzymes
Abdominal distention
Rectal prolpaspe
Fatty, stinky stools (Steatorrhea)
Meconium ileus in newborn.

24
Q

How does CF affect sweat?

A

Norm CFTR channel protein - reabsorbed Cl-/HCO3- from the epithelial surface
Failure to reabsorb leads to greater conc of Cl- on surface, greater conc of Na+, leads to large volumes of very salty sweat.

25
Q

What are the different types of cystic fibrosis?

A

Classic - diagnosed in early life, affects multiple organs and is more severe
Atypical - milder, one organ or symptoms that come and fo, usually diagnosed in older children or adults.

26
Q

What tests are done in the monitoring of cystic fibrosis?

A

Sputum culture - pathogen identification, guiding antibiotic therapy
Pulmonary function tests - lung function, disease progression and treatment efficacy
CT (potentially) - bronchiectasis, pneumothorax
Blood tests - for cystic fibrosis related diabebtes with oral glucose tolerance tests
Bone density assessment: DAX scan - for bone mineral density for osteopenia or osteoporosis.

27
Q

What are the different types of mutations seen in cystic fibrosis?

A

Class 1: defective protin synthesis - null mutation causing premature termination
Class 2: abnormal protein folding/processing - this is most common type F508del - CFTR degraded before inserted
Class 3: defective regulation (gating mutation) preventing activation of functional CFTR - inserted but not functional
Class 4: Decreased conductance - reduced function
Class 5 - reduced abundance (production mutations) - CFTR promotor
Class 6 - instability mutations - decreased membrane CFTR mutation.