Cystic Fibrosis

Vinay Kumar M
176312990003
A chronic, progressive, and frequently
fatal genetic disease of the bodys
mucus glands.
Affects the respiratory and digestive
systems in children and young adults.
An average person has a lifespan of
40 years with the right treatment.
Cystic Fibrosis: How Common?
Cystic Fibrosis is the most common serious
inherited disease
The most common cause of exocrine pancreatic
insufficiency in children
The most common cause of chronic lung
disease in children
Autosomal recessive
Incidence 1:3200 live births (Caucasians)*
1:28 Caucasians are carriers



Cloning of the Normal Gene
In 1990, scientists cloned the normal
gene, adding it to the CF cells in the
laboratory where it corrected the
defective transport mechanism.

Causation
Cystic Fibrosis is caused by a defective CFTR
gene which codes for a Na+ and Cl- transporter
found on the surface of epithelial cells of lungs
and other organs. As many as 1300 mutations in
the CFTR gene have been observed worldwide.
The severity of the disease is directly related to
the characteristic effects of the particular
mutations that have been inherited by the
individual sufferer.
Pathophysiology
CFTR mutations affect epithelial cells, thus
affecting:
Airways (sinuses, lungs)
Pancreas (endocrine and exocrine)
GI tract (liver/biliary system, intestines)
Reproductive organs
Skin

CF Lung
Chloride does not get into airway;
more sodium leaves; mucus is thick

CF: Lung lesions


Result from a combination of:
Abnormal concentrations of ions and water
in the airways.
Increased binding of bacteria.
Uncontrolled oxidation of fatty acids in the
cell membranes.


CF: Symptoms
The body produces thick, sticky mucus in the
lungs which becomes a breeding ground for
infection.
The pancreas becomes blocked by mucus,
unable to release digestive enzymes into the
intestines needed for digestion and
absorption of nutrients.
Excess mucus production impairs
reproductive organ functions in both males
and females.
Clinical Manifestations
Respiratory Tract
Cough is the most constant symptom.
Wheezing
Recurrent chest infection
Cyanosis is a late sign
Atelactasis, hemoptysis, pneumothorax,
and cor pulmonale
Sinusitis, nasal polyps

Clinical Manifestations.
Intestinal Tract
1. Meconium ileus 10-20%
2. Meconium plug syndrome (meconium
ileus equivalent)more than 85% of
patients showed evidence of
maldigestion from exocrine pancreatic
insufficiency.
3. Intussception

Clinical Manifestations
4. Bile or acid reflux with oesophagitis
5. Sub acute appendicitis
6. Rectal prolapse
7. Failure to thrive
8. Fat-soluble vitamin deficiency
manifestation.
Clinical Manifestations
Biliary Tract
Biliary cirrhosis symptomatic in 2-3% .
Ascitis, Jaundice, hematemesis,
esophageal varices
Neonatal hepatitis

Clinical Manifestations
Diabetes Mellitus 8% after the age of
10.
95% of males are azoospermic because of
failure of development of wolffian duct
structure.
Secondary amenorrhea
Cervicitis
Hypochloremic alkalosis
Presenting features of more than 20,000 CF
patients in USA
Feature %
Acute or persistent respiratory symptoms 50.5
Failure to thrive 42.9
Abnormal stool 35.0
Meconium ileus, Intestinal obstruction 18.8
Family history 16.8
Electrolytes, Acid-base abnormality 5.4
Rectal prolapse 3.4
Nasal polyps, sinus disease 2.0
Hepatobiliary disease 0.9
Other 1-2
Diagnosis of Cystic Fibrosis
Sweat test
Blood tests
Chest x-rays


Sputum cultures
Pulmonary
function tests
Stool evaluations
Pancreatic
function tests
The Sweat Test

Gold Standard for testing over 40 years
- painless
- inexpensive
- gives definite answers
The Sweat Test

Cl
-
60 mEq/L

40-60 mEq/L ?
MANAGEMENT
Cystic Fibrosis: A
Disease for a
Multidisciplinary Team
CF Team

Clinic coordinator
Social worker
Respiratory therapist
Nurse
Registered dietitian

MANAGEMENT
The Principles:
1. To Allow the child and his family, as far as
possible, to enjoy a normal lifestyle.
2. To minimize the emotional problems that
invariably develop.
3. To prevent, or at least retard as far as
possible, progressive lung disease.
4. To achieve optimal nutrition and maintain
normal growth
Management of Lung Disease
The aim is:
1.Clear secretions
2.Control infection
Management of Lung Disease
1. PHYSIOTHERAPY and physical activity
Chest physiotherapy
Postural drainage
Positive expiratory pressure
Agents to promote airway secretion clearance
-Hypertonic saline
-DNase I (dornase alfa)
-N-acetylcysteine


Management of Lung Disease

ANTIBIOTIC THERAPY

1. IV Antibiotics
2. Aerosolized Antibiotics
3. Oral Antibiotics
Antibiotics
Often unable to eradicate the organism
Determining optimal delivery mode for a
drug is difficult
CF patients require higher doses
Altered volume of distribution
Rapid clearance of drugs

IV Antibiotics
Indications:
1.Severe exacerbations
2.Bacterial resistance to all orally
administered antibiotics
3.Failure of oral antibiotic therapy to resolve
symptoms
Management of Lung Disease
BRONCHODILATOR THERAPY
Beta2 agonist

ANT-INFLAMMATORY AGENTS
Corticosteroids for Bronchopulmopnary
aspergillosis

TREATMENT OF PULMONARY
COMPLICATIONS
Management of G.I.T.
Manifestation
Nutrition is closely tied to overall health
Malnutrition in CF associated with
Stunted growth
Pubertal delay
Deterioration of lung function
Early death

G.I.T. Management
Pancreatic enzyme replacement (enteric
coated granules)
Lipase, Amylase, Protease
Not more than 2500 lipase units/kg/meal

Vitamin and Mineral supplements
Fat-soluble vitamins (A, D, E, K)



G.I.T Management
Treatment of G.I.T complications
-Meconium ileus
Meconium ileus Equuivalent
GER
Rectal Prolapse
Liver Disease
The most common complications
are chronic respiratory infections
Pneumonia, recurrent
Pneumothorax
Coughing up blood
Chronic respiratory failure
Cor pulmonale
Liver disease
Diabetes
Osteoporosis and arthritis