Cystic Fibrosis Flashcards
What is Cystic Fibrosis?
Chronic, multisystem disease
Primary morbidity and mortality: Respiratory complications
Additional manifestations: Digestive, reproductive, and integumental system
Autosomal Recessive
What is the CFTR protein?
CF gene encodes for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein
- Ion channel that controls movement of Na and H2O into and out of cells
–> mutations alter this function
What are the types of CFTR mutations?
Class I: lack of protein production
Class II: Protein trafficking defect - early degeneration
Class III: Defective regulation
Class IV: Reduced chloride transport through CFTR
Class V: reduced production
Class VI: decreased stability of CFTR
How is a diagnosis of CF made?
If the patient has One of these:
>=1 typical phenotypic features of CF
- Sibling with CF
- Positive newborn screening test
- *PLUS** one of these:
- Elevated sweat chloride on 2 occasions
- 2 known disease-causing CFTR mutations
- Abnormal nasal potential difference
What are the two primary systems involved in CF?
Respiratory system
Digestive system
What is the characteristic presentation of respiratory disease in CF?
Lung infection and inflammation can occur shortly after birth
- Cycles of infection and inflammation damage the lungs and decrease lung function (FEV1)
Incidence of pulmonary exacerbations increases with age
Progressive lung diseasse is the leading cause of death in CF
What are the pulmonary manifestations of CF?
- Chronic cough
- Sputum production
- recurrent infection
- bronchiectasis
- hemoptysis
- Pneumothorax
- Allergic bronchopulmonary aspergillosis
- Pulmonary arterial HTN
- Respiratory insufficiency/failure
What is the pathogenesis of Lung disease in CF?
Abnormal CFTR gene –> abnormal CFTR protein –> Abnormal Salt transport –> abnormal mucus –> impaired clearance –> infection –> inflammatory response –> bronchiectasis
How does CF affect lung clearance?
Normally, mucociliary transport in the lungs is dependent on movement of mucus by ciliated airway epithelial cells
–> cilia beat freely within an airway surface fluid layer which is maintained through a balance of chloride secretion and Na absorption
In CF, too little chloride is pumped out of the epithelial cells and too much Na is reabsorbed; H2O follows Na and the mucus becomes depleted
–> cilia are compressed and can no longer beat freely, and mucostasis occurs
What happens to mucus producing goblet cells in CF?
They undergo both hyperplasia and metaplasia, with extension into bronchioles where they are not usually seen
Submucosal glands are also hypertophied, leading to increased mucus production
How does infection affect mucus in CF patients?
Chronic inflammation, with neutrophilic invasion and lyses within CF mucus, as well as chronic infection, result in highly thickened secretions
–> adding to the already thickened mucus
–> this thickened secretions and mucus lead to increased susceptibility to bacterial infection, further affecting the lungs of a CF patient
When do structural changes in CF lung disease begin to occur?
Early!
In mild forms of CF, changes are seen as early as 6yrs old
How can airway clearance be improved with CF?
High frequency chest wall oscillation
–> literally shake mucus loose, then “huff cough” to remove mucus
What are the common phenotypic features of CF?
CF PANCREAS
- *C**hronic respiratory disease
- *F**ailure to thrive
- *P**olyps (nasal)
- *A**lkalosis, metabolic
- *N**eonatal intestinal obstruction
- *C**lubbing of fingers
- *R**ectal prolapse
- *E**lectrolytes increased in sweat
- *A**spermia/absent Vas Deferens
- *S**putum - S.aureas/P.aeruginosa
What is the sweat test used for diagnosis of CF?
Mild electrical current pushes medicine into skin to cause sweating
–> sweat is collected and salt content is measured
Results:
> 60mmol/L = CF
40-60mmol/L = borderline-further investigation needed
>29 mmol/L in infants is borderline
What is the nasal potential difference used to diagnose CF?
Measures Cl ion secretion of CFTR protein after isoproterenol challenge
–> absent in CF nasal epithelium
- Technically challenging; lab must do regularly to be good at it
What is the newborn screening used to screen for CF?
Immunoreactive trypsinogen (IRT)
–> cutoff varies by state
IRT (pancreatic enzyme precursor, elevated in CF) –> if elevated, get Mutation analysis –> if positive get Sweat test because there are many normal mutations of CFTR
How are CF patients’ respiratory disease monitored?
Isolation of organisms from sputum cultures is completed on a regular basis
- -> Must tell the lab it is a CF patient
- Specimen will be handled differently
- All Gram(-) isolates will be identified
- Mucoid samples will be processed by hand
