Cystic fibrosis

Pathogenesis: –

Cystic fibrosis (CF) is the most common lethal genetic disease in white populations. It is caused by a mutation in a gene that encodes cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is expressed in many epithelial and blood cells.

The primary function of the CFTR protein is as an ion channel that regulates liquid volume on epithelial surfaces through chloride secretion and inhibition of sodium absorption. It is also involved in bicarbonate-chloride exchange. A deficiency of bicarbonate secretions leads to poor solubility and aggregation of luminal mucins.

Decreased hydration of mucus makes it stickier to bacteria, resulting in infection and inflammation as well as obstruction of glandular ducts. It also results in viscid secretions in the respiratory and Gastrointestinal (GI) tract, pancreas, sweat glands and other exocrine tissues. The increased viscosity of these secretions makes them difficult to clear.

Respiratory system

Viscous secretions and poor clearance lead to colonization with pathogenic bacteria. The most common infecting bacteria are: –

Pseudomonas aeruginosa
Staphylococcus aureus
Haemophilus influenza
Stenotrophomonas maltophilia
Burkholderia cepacia complex organisms
A typical mycobacteria

Almost 1 in 5 adults with CF will suffer a secondary spontaneous pneumothorax. The cause of death in 90% of patients with CF is respiratory infection and the most common colonising bacteria are P aeruginosa and S aureus.

The musculoskeletal system

Poor nutrition and vitamin D deficiency, chronic inflammation, reduced weight bearing exercise and steroid use results in osteoporosis. Adults with CF have twice the risk of fractures

Gastrointestinal system

Abdominal pain is a frequent complaint in CF and the second most common reason for admission. Of all the causes only distal intestinal obstruction syndrome (DIOS) is unique to CF. GORD, biliary disease and constipation are more common in patients with CF due to abnormal motility.

90 % of CF patients have pancreatic insufficiency. Abnormal CFTR function in the pancreatic ducts causes loss of enzyme rich digestive secretions and bicarbonate. Ductal obstruction and proximal inflammation contributes to destruction and fibrosis of pancreatic tissue. Consequently, absorption of lipids and fat-soluble vitamins (A, D, E, and K) is reduced, which can lead to steatorrhoea, malabsorption and malnutrition.

This pancreatic destruction leads to a loss of secretory cells, including insulin-producing cells in the Islets of Langerhans. The resulting CF-related diabetes (CFRD) is also aggravated by peripheral insulin resistance.

Faecal loss of bile acids is increased in CF, leading to a reduction in the bile-salt pool. About 30% of adult CF patients have a small, poorly functioning gallbladder and may develop gallstones.

In summary, Clinical manifestations of CF are: –

Organ System	Clinical Manifestation
Respiratory	Pulmonary exacerbation – Pulmonary infection – Bronchiectasis – Respiratory Failure Pneumothorax Haemoptysis Asthma – Sinusitis, nasal polyposis – Allergic Bronchopulmonary Aspergillosis (ABPA)
Gastrointestinal	Constipation – Distal Intestinal Obstruction Syndrome (DIOS) – Intussusception Pancreatitis (in pancreatic sufficient patients) – Gastro Oesophageal Reflux Disease (GORD) Gastritis, peptic ulcer disease Biliary fibrosis, cirrhosis Portal Hypertension, variceal bleeding Appendiceal disease GI cancer Colonic strictures, fibrosing colonopathy Clostridium difficile colitis
Musculoskeletal	Osteoporosis – Pathological fractures Arthropathy – CF related Arthritis
Other	Renal calculi – Renal failure CF Related Diabetes (CFRD) Port (Totally Implantable Venous Access Device) 98% Male infertility – Reduced female fertility – Delayed puberty

Notes on the Management of CF presenting patient: –

Discuss patients with CF presenting to the ED with the regional CF centre.
Consider a diagnosis of CF in adults presenting with recurrent respiratory infections or pancreatitis.
TIVADs should only be accessed by staff that are trained to do so
Chest x-rays are useful in the diagnosis and evaluation of respiratory complications of CF, however comparison with previous films is often required.
Pulmonary exacerbations may present without pyrexia, new x-ray changes or leucocytosis. So, consider respiratory infection in the absence of new chest signs, and in the absence of any new chest X-ray changes.
Antibiotic treatment is required for most respiratory complications of CF. Be aware of drug allergies and recent sensitivities when selecting the appropriate antibiotic.
DIOS and fibrosing colonopathy are unique to CF all other causes of abdominal pain in the general population also present in patients with CF and with the same signs and symptoms.
CF is one of a few conditions where plain abdominal x-rays are recommended for evaluation of abdominal pain.
DIOS is managed medically in most cases, with surgical treatment generally resulting from failed, delayed or inappropriate medical therapy.
Have a high index of suspicion for fractures in patients with CF presenting with seemingly innocuous mechanisms of injury.