Cystic Fibrosis Pathophysiology

What is cystic fibrosis?

a rare, autosomal recessive genetic disease which can affect lung function, digestion, endocrine function, sweat production, and reproductive function

What causes cystic fibrosis?

a pathogenic mutation in a single large gene located on human chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein

What is the root cause of cystic fibrosis?

altered chloride transport out of cells (dependent on the class of the mutation)

What race are most of the cystic fibrosis population?

white

True or False: the CF population is growing more diverse every year

true

How many people have CF in the US?

~30,000

How many children are born with CF in the US annually?

~1,000

What does morbidity and mortality outcomes in CF depend upon?

disease genotype/severity, patient management, and compliance with therapies

What is the prevalence of the different CFTR mutations?

class II >>> Class I > Class III ~ Class IV > Class V/VI

In general, which mutations cause more severe disease?

Class I to Class III

How many CFTR mutations have been identified since the discovery of the gene?

more than 2,000

What is the normal physiology?

CFTR is created, reaches cell surface and functions properly, allowing transfer of chloride and water

What is a class I mutation?

no functional CFTR created

What is a class II mutation?

CFTR protein is created, but misfolded, keeping it from reaching the cell surface

What is a class III mutation?

CFTR protein is created and reaches the cell surface, but the gate does not function properly

What is another name for a class III mutation?

Gating mutation

What is a class IV mutation?

the opening of the CFTR protein ion channel is faulty

What is a class V mutation?

CFTR is created in insufficient quantities

What organs are involved/affected by cycstic fibrosis?

sinuses, lung, skin, liver, pancreas, and intestine

How does CF affect the lungs?

leads to frequent lung infections, an enlarged heart, and trouble breathing

What is the median FEV1 for 10/18/30 year olds with CF according to 2023?

102/102/84

What is the pathophysiology of pulmonary disease in CF?

mutated CFTR gene → loss of CFTR function → impaired bacterial eradication → infection → inflammation → airway remodeling → airway obstruction → bronchiectasis

What symptoms are associated with CF pulmonary disease?

cough, sputum production, shortness of breath/difficulty breathing

What signs are associated with CF pumonary disease?

reduced FEV1 and FVC, crackles/rales, rhonchi, wheezing, recurrent pneumonia, hyperinflation and atelectasis, late stage: pulmonary hypertension (cor pulmonale)

How does CF effect the pancreas/ exocrine functions of the body?

trouble digesting food, abnormal pancreas function, fatty bowel movements

What exocrine deficiencies are seen in CF patients?

protease, amylase, lipase, and bicarbonate

What does long term exocrine dysfunction in CF lead to?

acinar cell destruction → fibrosis → progressive adipose replacement of pancreatic tissue

What do acinar cells do?

secrete digestive enzymes

What does exocrine dysfunction in CF lead to acutely?

poor absorption of fat-soluble vitamins (ADEK) and zinc

What symptoms are associated with poor digestion in CF?

abdominal distention, increased stool frequency with loos consistency, increased fecal fat content/foul odor

True or False: there is an association between optimal BMI and better pumonary function

true

What is CFRD (cystic fibrosis related diabetes) caused by?

abnormal pancreas function; diminished insulin and glucagon secretion; insulin resistance is dynamic, variable, and progressive