Cystic Fibrosis

Cystic Fibrosis Study Notes

Definition

• Cystic fibrosis (CF) is described as an autosomal recessive disease.

• It is caused by mutations in a gene that codes for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein located on chromosome 7.

• The primary pathological mechanism involves the abnormal transport of chloride and bicarbonate across epithelial surfaces.

Autosomal Recessive Etiology

• CF is inherited in an autosomal recessive manner, meaning two copies of the defective gene must be present for the disease to manifest.

Pathogenesis

• The pathogenesis of cystic fibrosis can be classified into five categories, highlighting various defects in the CFTR protein function:

  • Category I: Protein production defect

  • Category II: Protein processing defect

  • Category III: Gating defect

  • Category IV: Conduction defect

  • Category V: Insufficient protein defect

Pathophysiology

• Patients with cystic fibrosis experience:

  • Excessive production and accumulation of thick, tenacious mucus on the mucociliary escalator, which is due to dehydration of the sol layer.

  • Impaired ability to clear secretions leads to:

  • Increased Raw (airway resistance)

  • Decreased airway radius, resulting in:

    • Inflammation

    • Bronchospasm

  • Partial bronchial obstruction can lead to:

  • Air trapping/hyperinflation

  • Total bronchial obstruction results in atelectasis.

  • Patients are more susceptible to frequent pulmonary infections due to compromised mucociliary function.

Clinical Manifestations

• Clinical symptoms typically present in infancy and include:

  • Symptoms:

  • Fatty, foul-smelling stools

  • Failure to thrive

  • Bowel obstructions

  • Dyspnea

  • Abdominal/GI discomfort

  • Increased appetite

  • Signs:

  • Increased vital signs

  • Pursed lip breathing

  • Cyanosis

  • Digital clubbing

  • Peripheral edema

  • Jugular venous distension (JVD)

• Chest Assessment findings reveal:

  • Palpation:

  • Increased anterior-posterior (AP) diameter

  • Decreased chest wall expansion

  • Use of accessory muscles during exacerbations or acute illness

  • Auscultation:

  • Diminished breath sounds

  • Presence of crackles

  • Wheezing

  • Sputum characteristics:

  • Copious and tenacious

  • High white blood cell (WBC) count

  • Evidence of bacterial colonization

Secondary Conditions

• CF often leads to several secondary conditions, including:

  • Bronchiectasis

  • Cor pulmonale

  • Pulmonary hypertension

  • Lung abscesses

  • Atelectasis

  • Spontaneous pneumothoraxes

  • Pulmonary infections

  • Sinusitis

  • Malnutrition

  • Bowel obstructions

  • Diabetes

  • Appendicitis

  • Pancreatitis

  • Gall bladder disease

  • Infertility

  • Decreased bone density

  • Anemia

Diagnostic Testing

• Diagnostic procedures for cystic fibrosis include:

  • Arterial Blood Gases (ABG):

  • Mild to moderate cases may show uncompensated or partially compensated respiratory alkalosis.

  • Severe cases may present with respiratory acidosis, potentially accompanied by hypoxemia.

  • Sputum Culture:

  • Frequent bacterial colonization observed.

  • Complete Blood Count (CBC) with Differential:

  • May reveal increased WBC count indicative of inflammation.

  • Possible findings of polycythemia or anemia.

  • Electrolyte Panel:

  • Assessment for electrolyte imbalances.

  • Pulmonary Function Testing:

  • Direct and indirect spirometry shows primarily obstructive disease or mixed disease characteristics.

  • Chest X-ray (CXR):

  • Findings may include:

    • Translucent lungs

    • Depressed or elevated hemidiaphragm

    • Right ventricular enlargement

    • Possible atelectasis

    • Bronchiectasis

Diagnosis

• Diagnosis of cystic fibrosis involves several screening and testing methods:

  • Newborn Screening

  • Sweat Chloride Test

  • Genetic Testing

  • Stool Fat Concentrations

  • Nasal Action Potential Difference testing

Treatment

• Current treatment options for managing cystic fibrosis include:

  • Administration of pancreatic enzymes

  • Provision of nutritional supplements and support

  • Delivery of preventative vaccinations

  • Implementation of aggressive airway clearance therapy

  • Use of bronchodilators

  • Application of mucolytics

  • Supplemental oxygen (O2)

  • Use of nebulized and systemic antibiotics

  • Recently developed medication Trikafta

  • In advanced cases, lung transplantation may be considered.

Prognosis

• The prognosis for cystic fibrosis patients is highly dependent on the category of mutation involved.

• Current projections indicate that those born with CF since 2020 are expected to live beyond the age of 65.

• The most common causes of death in CF patients tend to be respiratory or cardiac failure.