Module 5 Logbook - Cystic Fibrosis

Front 1

Definition

Back 1

Life-shortening genetic disease resulting from abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs

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Epidemiology

Back 2

1/2500 newborns.

Carrier frequency of 1/25

Autosomal (not a sex chromosome) recessive

More common in white Europeans

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Genetics

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Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, on chromosome 7

At least 1,500 mutations

Most common (80%) delta-F508

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Pathophysiology - cystic fibrosis transmembrane conductance regulator (CFTR)

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Lots of ways this can go wrong - doesn't open well, not enough etc

>>> Can't get chloride out of cells >>> too much sodium in >>> Attracts too much water >>> dehydrated viscous mucus

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Systemic effects - non respiratory

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High sodium sweat - CFTR does not absorb chloride ions so sodium absorption prevented

Pancreatic insufficiency - enzymes normal but ion transport defects >>> dehydration of pancreatic secretions >>> stagnation in pancreatic duct

Biliary disease >>> (again ion transfer) bile becomes concentrated causing plugging and local damage

GI >>> Low-volume secretions of increased viscosity (consequences of pancreatic and biliary disease)

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Respiratory effects

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Dehydration of the airway surfaces reduces mucociliary clearance and favours bacterial colonisation

Bacterial defences are impaired by local salt concentrations and bacterial adherence is increased by changes in cell surface glycoproteins

Inflammatory lung damage due to an exuberant neutrophilic response involving mediators such as IL8 and neutrophil elastase (bronchiectasis - abnormal widening of airways)

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Pathogens

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Bacterial: Haemophilus influenzae, Staph Aureus, Pneumococcus

Fungal: Aspergillus fumigatus

Rare: MRSA

DANGER - Pseudomonas aeruginosa - decline in lung function - 2-3xincreased risk of death over 8 years

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Classification

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With pancreatic insufficiency, with pancreatic sufficiency and atypical cystic fibrosis/other where there are symptoms but no known mutations

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Newborn screening

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Guthrie test - heel prick. Dried heel-stick blood spot. Quantifying serum immunoreactive trypsinogen

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Follow up investigations

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Sweat testing - 98% sensitive. Chloride concentration >60 mmol/L

Genetic testing

CXR or CT

Lung function

Sputum microbiology

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Presentation (non screening)

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Perinatal: bile not getting through from pancreas >>> green vomit, obstructed bowel and distended abdomen

Childhood: recurrent, infections, failure to thrive, nasal polyps

Adult: infertile, bronchiectasis + atypical asthma. Clubbing

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Management - respiratory

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Isolation (follow ups)

Immunisations + Pneumococcal and flu vaccine

Physiotherapy, acapella, physical activity

Medication: bronchodilators, prophylactic antibiotics and mucolytics

Monitoring

Surgery

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Management - non respiratory

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Nutrition - high fat, high calorie diet

CREON - pancreatic enzymes

Diabetes

Osteoporosis

Depression

Liver disease

Infertility (generally men)

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Prognosis

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Currently 38, thought to rise to 50 for those born now.

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OMEPRAZOLE

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PPI. Inhibition of H+/K+ATPase. Blocks the final step of acid production > reduction of gastric acid

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PANCREATIN

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Pancreatic enzymes. Lipase - hydrolyses fat. Protease converts protein. Amylase converts starch into dextrins and sugar

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SALBUTAMOL

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Beta 2 agonist. Increases cAMP, reduced phosphorylation of MLCK >> smooth muscle relaxation