CYSTIC FIBROSIS

INTRODUCTION:
  • Cystic fibrosis is an inherited disease of the mucus and sweat glands.
  • Cystic fibrosis follows on autosomal recessive transmission.
  • The most common inherited disorder of cholangiocyte injury is Cystic fibrosis
  • Staphylococcus aureus, Hemophilus influenzae, and Pseudomonas aeruginosa are common causes of respiratory infections in cystic fibrosis
  • There is a defect in ion transport of epithelial cells that affects fluid secretion in
  • Exocrine glands (pancreas)
  • Epithelial lining of respiratory, gastrointestinal and reproductive tract.
PATHOPHYSIOLOGY:
  • In normal duct epithelia, chloride is transported by plasma membrane channels (chloride channels)
  • The primary defect in cystic fibrosis results from abnormal function of an epithelial chloride channel protein encoded by the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q 31.2.
  • Protein encoded by CFTR is a chloride channel through which chloride passes
  • In cystic fibrosis activity of chloride channel is decreased.
  • Along with chloride channel, CFTR can regulate other channel also, for example epithelial sodium channels (ENaC).
  • ENaC is inhibited by normally functioning CFTR; hence, in cystic fibrosis, ENaC activity increases, markedly augmenting sodium uptake across the apical membrane (especially in respiratory and gastrointestinal system).
  • Normal CFTR gene product Defective (mutated) Crl R gene product in cystic fibrosis
  • Induce Cl- conductance through itself (chloride channel) → Reduced or lost Cl conductance
  • Inhibits Na+ conductance through → Augmented sodium uptake across apical membrane ENaC
CLINICAL FEATURES:
  • Functions of CFTR are tissue specific, i.e. its functions signify whether the epithelium is secretory (secrete Cl- into lumen) or absorptive (reabsorb Cl- from lumen). Therefore clinical features are tissue specific:
  • Lungs and sinus disease
Rhinosinustis
  1. Bronchiactasis
  2. Lower respiratory tract infection
  3. Nasal polyps
  4. Recurrent pneumonias
  5. Chronic lung disease
  • Pulmonary abscesses(P. aeruginosa infection)
  • Pulmonary hypertension can cause heart failure
  • Allergic bronchopulmonary aspergillosis
  • The earliest chest X-ray change in cystic fibrosis is Hyperinflation

GIT, Liver and pancrease
  • Meconium ileus
  • Rectal prolapse
  • Malabsorption
  • Pancreatitis
  • Constipation or diarrhea
  • Steatorrhoea
  • Intussusception
  • Meconium peritonitis
  • Bile duct obstruction and biliary cirrhosis
  • Cystic Fibrosis Related Diabetes Diagram

Endocrine(least affected)and growth
  • Diabetes
  • Xerophthalmia Osteoporosis
  • Poor growth
  • Exocrine pancreatic insufficiency
Infertility
  • In men due to absence of vas deference
  • In women due to thick cervical mucus
  • Azoospermia
  • Sweat glands
  • Loss of CFTR function leads to decreased reabsorption of NaCl→ Hypertonic sweat with increased Na+ and Cl in sweat
  • Sweat gland ducts are not obstructed in cystic fibrosis
DIAGNOSIS:

Risk Factor For CF Laboratory Evidence of CFTR Dysfunction
Presence of one or more typical clinical feature(> 1 phenotypic symptom) Positive sweat chloride test(>60 mcq/l on two occasions)
OR
History of CF in sibling Identification of 2 CF mutations
OR
Positive Neonatal screening test Abnormal Nasal Potential Difference
TREATMENT:
Lung
  1. Antibiotics
  2. Pseudomonas treated with two drugs with different mechanisms to prevent resistance
  3. e.g. cephalosporin + aminoglycoside
  4. Use of aerosolized antibiotics
  5. Increasing mucus clearance
  • N-acetylcysteine not clinically helpful
  • Long-term DNAse treatment increases time between pulmonary exacerbations
  • Inhaled b-adrenergic agonists to control airway constriction
  • Oral glucocoticoids for allergic bronchopulmonary aspergillosis
  • Studying benefits of high dose NSAID therapy for chronic inflammatory changes
Atelectasis
  1. Chest PT + antibiotics
  2. Respiratory failure and cor pulmonale
  3. Vigorous medical management Oxygen supplementation
  4. Only effective treatment for respiratory failure is lung transplantation
  5. 2 year survival >60% with lung transplantation
Gastrointestinal
  • Pancreatic enzyme replacement
  • Replacement of fat-soluble vitamins- especially vitamin E & K
  • Insulin for hyperglycemia
  • Intestinal obstruction
  • Pancreatic enzymes + osmotically active agents
  • Distal- hypertonic radiocontrast material via enema
  • End-stage liver disease- transplantation: 2 year survival rate >50%
  • Hepatic and gallbladder complications treated as in patient without CF
Exam Question
  • Cystic fibrosis can cause diarrhea
  • Staphylococcus aureus, Hemophilus influenzae, and Pseudomonas aeruginosa are common causes of respiratory infections in cystic fibrosis
  • Rhinosinustis is a common finding in CF
  • The most common cause of pulmonary abscesses in Cystic Fibrosis is Pseudomonas aeruginosa
  • Cystic fibrosis affects Respiratory, Hepatobiliary & Genitourinary systems
  • Most common organism associated with cystic fibrosis is Pseudomonas aeruginosa
  • Meconium ileus is associated with Cystic fibrosis
  • Sweat chlorides are increased in Cystic fibrosis
  • Cystic fibrosis (CF) is an Autosomal Recessive Disorder
  • Cirrhosis is an established complication of CF
  • The earliest chest X-ray change in cystic fibrosis is Hyperinflation
  • Steatorrhoea, Hypochloremia, Recurrent pneumonias are seen in a patient with cystic fibrosis
  • The most common inherited disorder of cholangiocyte injury is Cystic fibrosis
  • Intracanalicular hepatic apparatus is affected by Cystic fibrosis
  • Cystic fibrosis is Associated with CFTR gene
  • Cystic fibrosis is associated with Infertility, Azoospermia, Nasal polyps
  • Chromosome defective in cystic fibrosis is Chromosome 7
  • 3 episodes of chest infection and passage of foul smelling stools is diagnosed with Cystic Fibrosis
  • Cause of thick pancreatic secretions in cystic fibrosis Defect in chloride channel leading to water reabsorption
  • Most common pathogen causing, pulmonary infection in cystic fibrosis in infants & young children is Staphylococcus Aureus
  • Xerophthalmia is caused by cystic fibrosis
  • Exocrine pancreatic insufficiency is caused by cystic fibrosis
  • Central bronchiectasis is seen with Cystic fibrosis
  • Sweat gland ducts are not obstructed in cystic fibrosis
  • Chance of having cystic fibrosis if only one parent is affected and other is normal is 50%
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