Cystic Fibrosis & Sarcoidosis Flashcards
Cystic Fibrosis (CF) is an autosomal recessive condition
resulting in increased sodium absorption and abnormal chloride secretion in the epithelial cells lining the airways. This leads to thicker mucus impairing the function of cilia.
Describe the main innate defence mechanisms of the respiratory tract against inhaled pathogens
Mechanical
* Nasal Hair: Blocks and collects dust, pollen and other particles that could enter the lungs. Coated by a thin layer of mucus which helps those particles stick to the hair. These trapped particles are either swallowed or sneezed
* Mucociliary System
Chemical
* Lysozymes: An enzyme that hydrolyses the polysaccharides of bacterial cell membranes.Found in bodily secretions such as saliva and mucus
* Lactoferrin: Prevents transport of extracellular virus into host cells
* Defensins: Multiple antiviral mechanisms
* Surfactant: Opsonisation
Cellular
* Phagocytes (Alveolar Macrophages) – phagocytosis
* Dendritic Cells – antigen presenting cell
Normal Flora
* Provides competition for nutrients
* Production of toxic compounds
Describe the main adaptive defence mechanisms of the respiratory tract against inhaled pathogens
- Dendritic cells present antigen to
- T cells which become activated
- CD4 cells can generate specific immune response
- CD8 cells can lyse infected cells
- NK Cells produce IL-4, IFN gamma
Describe the mucociliary system function
The mucociliary transport system is another one of the lung’s mechanical innate defences. It protects the conducting airways by trapping and removing bacteria, inhaled particles, and cellular debris from the lung.
Effective clearance requires both ciliary activity and respiratory tract fluid (periciliary fluid and mucus). Inhaled material is trapped in tenacious and viscous mucous. The watery periciliary fluid allows the cilia to move freely with only their tips contracting the mucus and propelling it towards the mouth. Cilia moves the mucus up the tract by coordinated contraction called cilia beating.
Discuss the basic epidemiology of cystic fibrosis
CF is the most common inherited lethal disease.
1 in 2500 babies born in the UK have CF - 5 per week
1 in 25 carry the CF gene
Highest prevelance in Europe, N Ameria & Australia
Discuss the basic genetics of cystic fibrosis
Cystic Fibrosis (CF) is an autosomal recessive condition caused by a mutation in chromosome 7 at the CF transmembrane conductance regulator (CFTR) gene.
The result of this mutation is increased sodium absorption and abnormal chloride secretion in the epithelial cells lining the airways. This leads to thicker mucus impairing the function of cilia.
Discuss the basic pathophysiology of cystic fibrosis
- CFTR gene is rendered ineffective or damaged due to mutations
- This results in impaired ion [Chloride, Sodium] transport across membranes.
- This causes dehydration of the airway surface liquid, which in turn results in thick, viscous mucus → Obstructs airways
- This may lead to the introduction, colonisation and proliferation of bacteria in the bronchi → Bronchiectasis
- Chronic inflammation causes progressive loss of lung function
- CFTR dysfunction in the pancreas
Viscous secretions obstructing pancreatic ducts → Damage + Pancreatic insufficiency → Malabsorption, especially fat-soluble vitamins + fatty acids → Failure to thrive - CFTR dysfunction in the biliary epithelium → Cholestasis, bile duct construction + liver damage
- Men with CF may have a bilateral absence of the vas deferens → Infertility
Discuss the basic presentation & investigations of cystic fibrosis
PC
* neonatal period (around 20%): meconium ileus, less commonly prolonged jaundice
* recurrent chest infections (40%)
* malabsorption (30%): steatorrhoea, failure to thrive
* other features (10%): liver disease
*
newborn screening programmes or early childhood
5% of patients are diagnosed after the age of 18 years.
Other
* short stature
* diabetes mellitus
* delayed puberty
* rectal prolapse (due to bulky stools)
* nasal polyps
* male infertility, female subfertility
IX
* Sputum culture or throat swab: if symptomsof RTI
* Blood: Full Blood Count; Urea and Electrolytes; Liver Function Tests; Clotting studies; Vitamin A, D, E, K and Glucose levels
* Glucose tolerance test (to identify diabetes mellitus)
* Spirometry: obstructive defect
* Aspergillus skin prick test or serology
Imaging:
* Abdominal ultrasound: Distal Intestinal Obstruction; liver cirrhosis; chronic pancreatitis
* Chest X-ray: Hyperinflation, bronchiectasis
Discuss the basic management & prognosis of cystic fibrosis
The average life span for people with CF who live to adulthood is about 44 years
Management
* Fertility and genetic counselling
* Dietician
* Psychosocial counselling
* Chest physiotherapy: postural drainage & active cycle breathing
* Screening for complications of Cystic Fibrosis such as osteoporosis
* Potential surgical management - Lung Transplant
Infective exacerbations are treated with:
* antibiotics
* recurrent chest infections prophylactic long-term antibiotics may be prescribed.
* Nebulised mucolytics (Dornase Alfa)
* Bronchodilators (Inhaled corticosteroids or B2-agonists)
Everything else is treated as it comes
What is Sarcoidosis?
Sarcoidosis is a rare condition that causes small patches of swollen tissue, called granulomas, to develop in the organs of the body. It often affects the lungs and lymph nodes, and can also affect your skin.
It has no cure
Discuss the basic epidemiology & pathophysiology of sarcoidosis
- Second-most common chronic respiratory disease in the under-40s
- Most-often diagnosed between 25-40
- 30% of cases diagnosed in the over-65s
- Aetiology poorly understood; genetic predisposition plus exposure to antigen
- Disease involves the formation of non-necrotizing granulomas
- Can affect any organ system
- These granulomas are infiltrated by Th1 lymphocytes and macrophages, which fuse to form multinucleated epithelioid cells.
Pulmonary Pathology - Bilateral hilar lymphadenopathy in up to 90% of affected individuals
- Predominately upper lobe parenchymal infiltration
- Airway hyperresponsiveness leads to increased sensitivity to inhaled triggers
- Pulmonary hypertension -> cor pulmonale
Discuss the basic presentation of Sarcoidosis
Varies by organ & may be asymptomatic
* Peripheral lymphadenopathy
* Fatigue, weight loss
* Erythema nodosum
* Arthralgia
* Dry eyes
* Lower Respiratory Manifestations
o Wheezing, Cough
o Dyspnoea
o Chest pain
o Haemoptysis
o Crackles
* Uveitis & Vision Loss
* Cardiac Collapse
* Seizures & Aseptic Meningitis
Can be acute (flu-like symptoms & good prognosis) or chronic (progressive symptoms with multiple organ involvement)
Discuss the basic investigations of Sarcoidosis
Blood tests
* FBC – normocytic anaemia
* U&Es – Renal dysfunction
* LFTs – Derangement (obstructive or hepatitic)
* Serum calcium – Granulomas secrete Vit D causing hypercalcaemia
* Serum Angiotensin Converting Enzyme (sACE) – elevated commonly but not specific – used to monitor disease activity
* Immunoglobulins – Association with Ig deficiencies (particularly IgA)
Pulmonary function tests - Any pattern can occur (obstructive most common)
CXR then CT chest
Radiographic Stages;
0 Normal
1. Bilateral Hilar lymphadenopathy
2. BHL & pulmonary infiltrates
3. pulmonary infiltrates without BHL
4. Advanced pulmonary fibrosis
ECG – heart block
Bronchoscopy for pulmonary sarcoidosis – GOLD standard for diagnosis
Discuss the basic management & prognosis of sarcoidosis
Most patients will not require immediate treatment; those with more severe disease will require early treatment
Treatment is indicated to improve quality of life or because of danger of damage to organs
First choice drug; Prednisolone
Second choice; Methotrexate
Others; Azathioprine, Mycophenolate, Hydroxychloroquine, Anti-TNF
Prognosis
* Usually considered a benign condition
* Life expectancy not considered to be any different from the general population, although quality of life can be impaired with major organ involvement
* Acute and incidental presentations have better outcomes
* CXR presentations also predicts outcome:
* Stage I – 60% resolution at 2 years
* Stage II – 46%
* Stage III – 12%
Mortality rate varies between 1-8% however with significant disease manifestations this can increase to around 25%
