Cystic Fibrosis | Cystic Fibrosis made easy

 Cystic Fibrosis. if you want to understand the topic of cystic fibrosis, then this is best place for you. Because we teach medicine for preparation of exams. we will teach you core concepts of cystic fibrosis...!

What is Cystic Fibrosis?

Cystic fibrosis is an inherited disorder that damages your lungs, digestive tract and other organs.

Genetics:

Autosomal recessive defect in CFTR gene on chromosome 7, commonly a deletion of Phe508. Most common lethal genetic disease in Caucasian population.

Pathophysiology:

CFTR encodes an ATP-gated Cl− channel that secretes Cl− in lungs and GI tract, and reabsorbs Cl− in sweat glands. Most common mutation is misfolded protein  leading to protein retained in RER and not transported to cell membrane, causing decreased  Cl− (and H2O) secretion, increased intracellular Cl− results in compensatory increase in Na+ reabsorption via epithelial Na+ channels (ENaC)  leading to H2O reabsorption , hence abnormally thick mucus is secreted into lungs and GI tract. Increased Na+ reabsorption also causes more negative transepithelial potential difference.

Clinical Symptoms:

• Recurrent sinopulmonary infections
• Intestinal obstruction (eg, meconium ileus)
• Pancreatic insufficiency & diabetes
• Male infertility . 

Pancreatic Insufficiency:

The most common gastrointestinal manifestation of CF is pancreatic insufficiency.  Pancreatic duct obstruction from viscous mucus prevents digestive enzymes from reaching the intestines and leads to progressive pancreatic inflammation and fibrosis.  Fat and protein malabsorption occur, leading to steatorrhea (bulky, greasy stools), growth failure, and fat-soluble vitamin deficiencies (ie, A, D, E, and K). 

Growth:

A typical CF growth chart shows normal birth measurements with subsequent failure to thrive, characterized by weight deceleration crossing ≥2 major percentiles (eg, 25th, 10th) followed by a deceleration in linear growth velocity.  In addition to malabsorption, recurrent sinopulmonary infections impair growth due to poor appetite and increased metabolic needs during illness. 

Infertility: 

Patients with obstructive azoospermia generally have normal spermatogenesis, but sperm cannot be ejaculated due to impaired transport.  Disorders of sperm transport primarily include abnormalities of the epididymis and vas deferens. 

Congenital absence of the bilateral vas deferens is characteristic of cystic fibrosis (CF) 

The accumulation of inspissated mucus in the fetal genital tract obstructs the developing vas deferens.  As a result, almost all men with CF are infertile without assisted reproductive technology (eg, sperm aspiration).  

Women with CF may have decreased fertility due to thickened cervical mucus but can get pregnant.

Pneumonia:

Most patients have chronic malabsorption and diarrhea as well as recurrent pneumonias that lead to irreversible bronchiectasis, chronic hypoxia, and progressive respiratory failure.  Hyperinflation of the lungs causes the rib cage to remain partially expanded, giving the appearance of a "barrel chest".  Bulbous enlargement of the tips of the digits (clubbing) occurs as well. 

The most common pathogen isolated from sputum cultures in infants and young children is Staphylococcus aureus, a gram-positive coccus that grows in clusters.  S aureus colonization decreases with age but remains a significant source of disease in adults with CF. 

Colonization and infection with Pseudomonas aeruginosa  can occur as early as infancy and is the most common cause of CF-related pneumonia in adults. 

Diagnosis:

• Elevated sweat chloride levels
• CFTR mutation on genetic testing
• Abnormal nasal potential difference

Management:

• Nutritional support
• Airway clearance
• Antibiotic coverage (Staphylococcus aureus, Pseudomonas aeruginosa)