Cystic Fibrosis

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
  1. Exocrine glands (pancreas)
  2. 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 
  • Bronchiactasis               
  • Lower respiratory tract infection
  • Nasal polyps        
  • Recurrent pneumonias
  • 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

Image result for CYSTIC FIBROSISImage result for CYSTIC FIBROSIS

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

  • Antibiotics
  • Pseudomonas treated with two drugs with different mechanisms to prevent resistance
  • e.g. cephalosporin + aminoglycoside
  • Use of aerosolized antibiotics
  • 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
  • Chest PT + antibiotics
  • Respiratory failure and cor pulmonale
  • Vigorous medical management
  • Oxygen supplementation
  • Only effective treatment for respiratory failure is lung transplantation
  • 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%
Don’t Forget to Solve all the previous Year Question asked on Cystic Fibrosis

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