CYSTIC FIBROSIS
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Transcript of CYSTIC FIBROSIS
ALOK SINHADepartment of Medicine
Manipal College of Medical SciencesPokhara, Nepal
Cystic fibrosis (CF) is an inherited disease of mucus glands of body causing progressive disability due to multisystem failure Affects mostly Lungs: chronic suppurative lung disease Pancreas:chronic exocrine pancreatic insufficiency liver intestines sinuses reproductive organs
• An abnormal gene causes mucus to becomeThick and sticky • gene is called CFTR Gene(cystic fibrosis transmembrane conductance regulator) This is also known as delta-F508 mutation
• This gene makes a protein-CFTR Protein • It controls movement of salt and water in
and out of the cells in body
The CFTR gene is found on the long (q) arm of human chromosome 7
Basic defect • Defective channel leads to a high concentration
of sodium & chloride in exocrine secretions (normally Chloride > Sodium in sweat but in CF Sodium > Chloride. Their level is half of Serum and K+ is double)
• Leading to thick viscous & difficult-to-clear
secretions in lungs and other orgnas mentioned earlier
• Patients with CF present with multi systemic disease involving several or all of the organs mentioned
Autosomal recessive disorder
INCIDENCEOne of the most common inherited diseases among CaucasiansAbout 1 in every 3,000 babies born in the United States has CF
heterozygotes (carriers) is estimated to be 5%
CF is much less common among:– Africans – Asians – 10 times less
Previously, CF was a childhood disease, it has become an adult pulmonary condition
Currently, one third of the population with this paediatric disease is adult, and patients as old as 60 years are seen
Median survival now 29-31 years
70% of patients, diagnosed prior to 1 year
In 8% of patients, the diagnosis is not established until after the age of 10 years
Diagnosed in an increasing number of adults
Features at the time of presentation
Meconium ileus: 10% of newborns present as intestinal obstruction in the first days of life– meconium ileus equivalent may occur in later life
Recurrent respiratory infections: common presenting feature
Failure to thrive affects about 50% of CF patients in childhood and infancy; as a result of pancreatic insufficiency
Respiratory manifestations
Thick mucus blocks the airways
Leads to bacterial growth, colonization & repeated serious lung infections leading to lung damage
Lungs are infected with – Staph. aureus initially– Pseudomonas aeruginosa by the time
they reach adolescence
There is frequent colonization and persistent infection by these bacteria
Chronic inflammation promotes tissue destruction via the excessive release of elastase by recruited neutrophils
Bronchiectasis with progressive productive cough and green/brown sputum multiple chest infections– initially in the upper lobes then through out
both lungsPneumothorax may occur
Aspergillus fumigatus and allergic broncho pulmonary aspergillosis may occur in some (20%)
Nasal polyposisEventually pulmonary fibrosis may lead to death from –cor pulmonale –ventilatory failure
OTHER SYSTEM INVOLVEMENT
Gastrointestinal manifestations
Pancreatic insufficiency leading to malabsorption and failure to thriveAcute pancreatitisIntrahepatic bile duct obstruction caused by abnormal inspissated bile causes– Liver cirrhosis– Portal hypertension
gynaecomastia and other signs of chronic liver disease eg hepatosplenomegaly
Distal ileus obstruction syndrome - meconium ileus equivalentRectal prolapse - due to bulky stoolsBiliary strictureGallstones, cholecystitisIntussusceptionComplications secondary to fat-soluble vitamin deficiency
Other manifestations
Infertility due to failure of development of the vas deferens - obstructive azoospermia
Affected females are subfertile
Hypertrophic pulmonary osteoarthropathy
Cystic fibrosis arthropathy
Diabetes mellitus - in 10-20% of adult patients – – a result of blockage of the pancreatic ducts due to
abnormal pancreatic secretions and autodigestion of the pancreas
Vasculitis, purpura
Salt loss syndrome - Acute salt depletion and chronic metabolic alkalosis
CLINICAL FEATURES
• Clubbing- constant feature• Features of hyperinflation
• Increased AP diameter of chest • Decreased expansion of lung• Hyperresonant percussion note & obliternation of
hepatic and card. dullness• Vesicular br. Sound with prolonged exp
• Features of bronchiectasis• clubbing & persistent coarse crepts
• Features of malabsorption
Lab investigations
Sweat test:Diagnostic of cystic fibrosis Induced by intra-dermal injection of pilocarpineChloride concentration > than 60 mmol/l Sodium concentration is greater than 70 mmol/l Sodium concentration is greater than chloride concentration in the sweat
Nasal potential difference testing
Individuals with cystic fibrosis have a raised potential difference across the nasal respiratory epithelium; 45 mV in comparison with 15 mV in normal individuals
ABG analysis- Hypoxemia Compensated resp Acidosis
P.F.T. Mixed Obstructive & Restrictive pattern
fecal fat and pancreatic-enzyme secretion tests
Semen analysis – azoospermia
Ultrasound abdomen – for pancreatitis and cirrhosis
Chest radiography
Chest radiographs may be normal in patients with CF who have mild lung disease
Hyperinflation is the earliest change initially reversible with treatment later becomes persistent
flattening of the diaphragm – classic sign caused by mucus plugging of small bronchioles
• as the disease progresses, bilateral, irregular, fine, blotchy shadowing appears in the middle and upper zones
• more advanced disease yields the radiological features of bronchiectasis, with:
thickened bronchial wallscystic shadows with fluid levels
1. Bilateral diffuse Multiple cavities 2. Bronchiectasis 3. Peribronchial fibrosis 4. Prominent hilum 5. Hyperinflated lungs
sputum cultureskin test for aspergillus as 20% develop allergic bronchopulmonary aspergillosisin severe cases arterial blood gas sampling shows chronic hypoxia and hypercapnia
glucose tolerance testmalabsorption screen: fecal fat estimationfull blood count - macrocytosis suggests vitamin B12 or folate deficiencycalcium - low in vitamin D deficiencyalbumin - protein losing enteropathy; for corrected calcium
severe bronchiectasis regular chest physiotherapymore frequently during exacerbationsinfections with Staph. aureus can often be managed with oral antibioticsI.V. treatment needed for PseudomonasNebulised antibiotic therapy with – Colomycin – Tobramycin
is used between exacerbations to suppress chronic Pseudomonas infection
bronchi of many CF patients become colonised with pathogens resistant to most antibiotics
strains of P. aeruginosa, Stenotrophomonas maltophilia require prolonged treatment with unusual combinations of antibiotics
oral macrolides such as azithromycin also reduce exacerbations and improve lung function in patients with Pseudomonas colonisation
coexistent asthma, which is treated with inhaled bronchodilators & corticosteroids
(allergic bronchopulmonary aspergillosis occasionally occurs in CF)
Nebulised recombinant human deoxyribonuclease (DNase)
liquify the CF sputum by breaking up the excess of viscous DNA derived from disintegrated inflammatory cells significant improvement in pulmonary function and a reduction in the number of infective exacerbations in a subgroup of patients treatment is very expensive
non-respiratory manifestations of CF clear link between good nutrition and prognosis Malabsorption is treated with oral vitamins and pancreatic enzyme supplements increased calorie requirements: supplemental feeding including nasogastric or gastrostomy tube feeding if requiredDiabetes often requires insulin therapy
Osteoporosis secondary to malabsorption and chronic ill health should be sought and treated
somatic gene therapy
Manufactured normal CF gene can be deliveredto the respiratory epithelium by inhaled therapyto correct the genetic defect
Future is always hopeful
Humanity will keep on wining