Cystic Fibrosis Flashcards
What type of genetic condition is cystic fibrosis?
Autosomal recessive condition where there is a mutation on chromosome 7 in the CFFTR gene for phenylalanine , encoding for ATP-gated Cl- channel. In the sweat glands, this causes reduced absorption of Cl- and loss of sodium and water on skin surface and in the GIT, lungs and pancreas, reduced secretion of Cl-.
On which chromosome is the CFTR gene located?
Chromosome 7
What does the CFTR gene encode for?
ATP-gated Cl- channel
What occurs in the sweat glands due to cystic fibrosis?
Reduced absorption of Cl- and loss of sodium and water
What is a common complication in the lungs due to cystic fibrosis?
Lung damage and fibrosis from elastase release
What is the Neonatal screening for cystic fibrosis?
heel-prick skin test.
Which two bacteria are commonly associated with recurrent infections in cystic fibrosis?
- Staphylococcus aureus
- Pseudomonas aeruginosa
What is the pathophysiology of cystic fibrosis?
Inflammatory response with proteases and cytokines causes lung injury, worsened by IL-8. This can result in Bronchieactasis overtime. Hypoxia can occur which results in pulmoanry hypertension and cor pulmonale
There is obstruction in pancreatic duct secretion, resulting in auto-digestion of the pancreas by digestive enzymes, increasing risk of diabetes mellitus in adults.
Thicker secretions in hepatobiliary secretions results in biliary obstruction and fibrosis.
Viscous intestinal secretions increases the risk of meconium ileus -> intestinal obstruction in neonates and adults
Majority of males are infertile due to poor development of vas deferens
Minority of female patients are infertile
What inflammatory response is worsened by IL-8 in cystic fibrosis?
Lung injury
What are the clinical signs of cystic fibrosis?
- Recurrent infection
- coughing
- wheezing
- disturbed sleep
*haemoptysis - steatorrhea
- malnutrition
*meconium ileus in neonates causing vomiting and abdominal distention
*clubbing and bilateral nasal polyps
What condition can develop over time due to lung damage in cystic fibrosis?
Bronchiectasis
What complication can occur due to obstruction in pancreatic duct secretion?
Auto-digestion of the pancreas
What is meconium ileus?
Intestinal obstruction in neonates caused by thick intestinal secretions
What is a common clinical sign of cystic fibrosis in males?
Infertility due to poor development of vas deferens
What are common clinical signs of cystic fibrosis? (List at least three)
- Recurrent infections
- Thick cough
- GI malabsorption
What are the complications with cystic fibrosis?
*Obstructive lung disease causes chronic respiratory acidosis, loss of fluid in sweat and the kidney attempts to compensate with contraction metabolic alkalosis
*Chronic inflammation of sinuses from increased mucous viscosity results in bilateral nasal polyps (soft growths), which increases the risk of pseudomonas aeruginosa infection
- Constipation and this increases risk of rectal prolapse
Infection with Burkholderia results in poor prognsois for lung transplant - Risk of pneumonia with pseudomonas aeruginosa
Obstruction of biliary system, that can lead to obstructive cirrhosis and post-hepatic hyperbilirubinaemia. There is also risk of portal hypertension
*Pancreatic insufficiency assoicated with diabetes
*Clubbing and cyanosis
*Electrolyte abnormalities with low sodium, chloride and potassium with possible metabolic acidosis
What is CFTR-related diabetes?
Cystic fibrosis related diabetes occurs due to abnormal glucose metabolism, due to CFTR mutation causing abnromal beta-cell function and structural damage from the auto-digestion of the pancreas, resulting in cyst formation and progressive fibrosis. First indication is failure to maintain or gain weight, with polyuria and polydipsia being less common.
Management is withn insulin therapy similar to type 1 diabetes using insulin doses for meals, with rapid-acting insulin and long-acting insulin. Thy rarely present with diabetic ketoacidosis and have lower insulin requirements than type 1 diabetics
Which airway condition are patients with cystic fibrosis at greater risk for?
Cystic fibrosis pulmonary sepsis is at greater risk in these patinets due to airways chronically colonised by pathogenic bacteria from an early age, due to impaired mucociliary clearance which can result in dyspnoea, increased volume of purulent sputum, haemoptysis, wheeze and chest ache. FEV1 levels are a marker for infection and decreases during these periods and improve with antibiotic therapy.
How does cystic fibrosis change with age?
There is a progression of airway colonisation over time, as organisms become more resistant to antibiotic from staphylococcus aureus, haemophilius influenzae and pseudomonas aeruginosa.
Most patients with CF by their early teens are chronically infected with pseudomonas aeruginosa intermittently. They are at more risk of respiratory infection with non-tuberculous mycobacteria abscessus, typically found in the environment.
How is cystic fibrosis diagnosed?
*Evidence of dysfunctional CFTR gene variants
*Heel prick immunoreactive trypsinogen newbornscrenening
Sweat testing for chloride, pancreatic elastase to measure disease progression
*CT imaging and spirometry
*Bronchoalveolar lavage will show high neutrophil count, due to inflammation from mucus obstruction
*Pulmonary function tests showing low FEV1/FVC ratio
*Regular physical exercise
What is the purpose of sweat testing in cystic fibrosis diagnosis?
To measure chloride levels
How is cystic fibrosis managed?
Management of cystic fibrosis surrounds maintaining lung function, nutritional support, GI screening for biliary cirrhosis and portal hypertension includes
vaccination and screening for diabetes.
airway clearance with nebuliser hypertonic saline and chest physiotherpay
Pulmonary management for acute cystic fibrosis exacerbation with pseudomonas aeruginosa using fluroquinolones such as ciprofloxacin
nutritional support and laxatives for constipation
pancreatic enzyme replacement
Optimising breathing with nasal cannula oxygen supplementation to improve exercise insurance and sleep quality
What is the typical FEV1/FVC ratio in cystic fibrosis patients?
Low
What is a key aspect of management for cystic fibrosis?
Maintaining lung function
