20.7
Fibrosi cistica: patogenesi
La fibrosi cistica (FC), una malattia autosomica recessiva, colpisce significativamente la funzione delle ghiandole esocrine. Questa malattia ereditar…
La fibrosi cistica, o FC, è una malattia autosomica recessiva che deriva da mutazioni nel gene CFTR sul cromosoma 7.
La fibrosi cistica deriva da oltre 2000 mutazioni all'interno del gene CFTR.
La proteina CFTR funziona come un canale ionico, regolando il trasporto di ioni cloruro e sodio nelle cellule produttrici di muco.
Le mutazioni possono causare una diminuzione della secrezione di cloruro e un aumento dell'assorbimento del sodio, producendo muco più denso e influenzando il sistema respiratorio.
Inizialmente, i polmoni di un paziente con FC sembrano normali, ma un effetto a cascata seguito da infezione e infiammazione porta all'ostruzione del muco all'interno dei bronchioli, causando una malattia polmonare ostruttiva.
La FC può assomigliare clinicamente alla bronchite cronica, alle bronchiectasie, all'asma atipico, all'aspergillosi broncopolmonare allergica e alle infezioni come Pseudomonas aeruginosa.
Lo screening diagnostico prevede test del cloruro nel sudore, del DNA e della differenza di potenziale nasale con conferma attraverso test di mutazione correlati alla FC.
I test di funzionalità polmonare sono fondamentali per monitorare la progressione della malattia.
View the full transcript and gain access to JoVE Core videos
Q1: What genetic mutation causes cystic fibrosis?
Cystic fibrosis results from mutations in the CFTR gene on chromosome 7, with over 2,000 known mutations identified. The most common mutation is ΔF508. These mutations disrupt the CFTR protein, which normally functions as an ion channel regulating chloride and sodium transport in mucous-producing cells, leading to thick, sticky mucus production.
Q2: How do CFTR mutations affect ion transport and mucus production?
CFTR mutations cause decreased chloride secretion and increased sodium absorption in mucous-producing cells. This ion imbalance reduces water secretion into mucus, resulting in thicker, more viscous secretions. The abnormal mucus accumulates in airways and ducts, obstructing normal function across multiple organ systems.
Q3: What happens to the lungs in cystic fibrosis patients?
Initially, CF lungs appear normal, but mutations trigger a cascade of infection and inflammation. Thick mucus plugs the bronchioles, causing obstructive lung disease. CF lung disease clinically resembles chronic bronchitis, bronchiectasis, and can involve colonization with Pseudomonas aeruginosa, leading to progressive airway damage.
Q4: Which organs are most commonly affected by cystic fibrosis?
CF primarily affects exocrine glands and multiple organ systems. The most commonly affected organs include sinuses, lungs, pancreas, liver and biliary systems, intestines, and sweat glands. Pancreatic involvement causes insufficiency and early-onset diabetes, while hepatobiliary manifestations include cirrhosis and portal hypertension.
Q5: How is cystic fibrosis diagnosed?
CF diagnosis requires clinical symptoms, positive family history, and confirmatory tests. The sweat chloride test measures elevated chloride levels in sweat. DNA testing identifies two disease-causing CFTR mutations, and nasal potential difference testing measures abnormal ion transport. Pulmonary function tests monitor disease progression and lung involvement.
Q6: What respiratory complications can develop from cystic fibrosis?
CF can clinically resemble chronic bronchitis, bronchiectasis, atypical asthma, and allergic bronchopulmonary aspergillosis. Mucus plugging in bronchioles causes obstructive airway disease and chronic infections. Abnormal pulmonary function tests reflect progressive lung damage, and bacterial colonization, particularly Pseudomonas aeruginosa, accelerates respiratory decline.
Q7: Why is cystic fibrosis classified as an autosomal recessive disorder?
CF is autosomal recessive because the CFTR gene mutation on chromosome 7 requires two mutated copies—one from each parent—for disease expression. Individuals with one mutated copy are carriers but typically asymptomatic. This inheritance pattern means affected individuals have carrier parents, and siblings have a 25% chance of inheriting the disease.