Transcript Slide 1

ALOK SINHA
Department of Medicine
Manipal College of Medical Sciences
Pokhara, 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 become
Thick and sticky
• gene is called
CFTR Gene
(cystic fibrosis transmembrane conductance regulator)
This is also known as delta-F508 mutation
The CFTR gene is found on the
long (q) arm of human
chromosome 7
• This gene makes a protein-CFTR Protein
• It controls movement of salt and water in
and out of the cells in body
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
INCIDENCE
One of the most common inherited
diseases among Caucasians
About 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 lungs
Pneumothorax may occur
Aspergillus fumigatus and allergic broncho
pulmonary aspergillosis may occur in some (20%)
Nasal polyposis
Eventually pulmonary fibrosis may lead to death
from
– cor pulmonale
– ventilatory failure
OTHER SYSTEM INVOLVEMENT
Gastrointestinal manifestations
Pancreatic insufficiency leading to
malabsorption and failure to thrive
Acute pancreatitis
Intrahepatic 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 equivalent
Rectal prolapse - due to bulky stools
Biliary stricture
Gallstones, cholecystitis
Intussusception
Complications 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 pilocarpine
Chloride 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 walls
cystic shadows with fluid levels
1. Bilateral diffuse
Multiple cavities
2. Bronchiectasis
3. Peribronchial fibrosis
4. Prominent hilum
5. Hyperinflated lungs
sputum culture
skin test for aspergillus as 20% develop
allergic bronchopulmonary aspergillosis
in severe cases arterial blood gas
sampling shows chronic hypoxia and
hypercapnia
glucose tolerance test
malabsorption screen: fecal fat estimation
full blood count - macrocytosis suggests
vitamin B12 or folate deficiency
calcium - low in vitamin D deficiency
albumin - protein losing enteropathy; for
corrected calcium
severe bronchiectasis
regular chest physiotherapy
more frequently during exacerbations
infections with Staph. aureus can often be
managed with oral antibiotics
I.V. treatment needed for Pseudomonas
Nebulised 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 required
Diabetes 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 delivered
to the respiratory epithelium by inhaled therapy
to correct the genetic defect
Future is always hopeful
Humanity will keep on wining