Flashcards in Lecture 10 - CF: Respiratory System Deck (65):
Describe the anatomy of the respiratory system
Series of branching tubes:
• Upper airways
• Terminal bronchioles
• Respiratory bronchioles
• Alveolar ducts
What is the difference between the conducting and respiratory zones?
Conducting: mucosa lined, no gas exchange
Respiratory: simple squamous epithelium for gas exchange
What are the phases of lung development?
1. Embryonic: lung bud appears, out pouching from foregut
2. Pseudoglandular: branching of airways up to terminal bronchioles
3. Canalicular: development of acinar region & type I and II pneumocytes
4. Sacular / alveolar:
• sacules form into alveolar ducts
• decrease in interstitial tissue, septation
• alveoli start to develop
What is the tissue origin of the lungs?
What is the acinus?
Of what is it composed?
This is the gas exchange region of the lung
• respiratory bronchioles
• alveolar ducts
• alveolar sacs
What is septation?
Septa form between alveoli to form more alveoli
What are some functions of the lungs?
• Gas exchange
• Acid-base balance
• Heat exchange
• Water balance
What are the defences in the lung?
• cough reflex
• mucociliary escalator
• turbinates, filter
• alveolar macrophages
What is ASL and what is it composed of?
Airway surface liquid:
• periciliary layer
• mucous gel layer
Describe the function of the mucociliary escalator
ASL present on cells in lumen
Cilia on apical surface beat 12-15 times per second
Describe gas exchange in the lungs
• Takes place at the level of alveoli
• Alveoli filled with air upon inspiration
• Gas diffuses in solution across the single celled wall of the alveolus into the capillary
• Basement membrane between alveolus and capillary
What is the measurement of 'Flow'
Volume / time (of air)
Which parameters do we measure to determine lung function?
What are the various lung volumes and capacities of the lungs?
Total lung capacity
Expiratory reserve volume
Inspiratory reserve volume
Describe how FEV and FVC are measured
1. Maximal inspiration
2. Forced expiration until residual volume
First second: FEV
Until residual volume: FVC
When is most of the air exhaled when performing Spirometry?
What happens with reversible intrathoracic airway obstruction?
Air can't be exhaled as quickly
What are some pulmonary complications of CF?
• Poor lung function, progressive decline
• Cough and sputum production
• Need for transplantation; death
• Respiratory failure
What causes lung disease in CF?
The CFTR mutation(s)
Which cells in the respiratory system express CFTR?
Epithelium of respiratory tract
Serous cells of submucosal cells
Type II pneumocytes
What is the role of CFTR in the epithelium of the respiratory tract?
Describe what happens to this process in CF
Modulates the composition of ASL
1. Cl- secretion through CFTR
2. Na+ and H20 absorption through ENaC
1. No Cl- secretion
2. No ENaC inhibition; increased Na+ and H2O absorption
3. Decrease in ASL volume
What are the sequalae of reduced ASL volume?
• Reduced ciliary beating in periciliary layer
• Decreased lubrication, adherence of mucous plaque
→ Promotes chronic infection
Discuss the interaction between CFTR and Bicarbonate ions
CFTR important for bicarbonate ion transport
Mutation leads to:
→ improper pH regulation of ASL (airway surface liquid)
→ inhibits antimicrobial function
What are the thick mucous plaques in the airways of CF patients?
Adhere to airway epithelial surface
Describe the anaerobic milieu
Increased oxygen consumption of epithelial cells
→ anaerobic environment
This anaerobic environment is ideal for the growth of bacteria
→ Pseudomonas aeruginosa converts to anaerobic biofilm mode of growth
What is the common feature of lung inflammation in individuals with CF?
Describe the effect of this
Presence of great n°'s of neutrophils, causing:
• tissue damage
• neutrophils possess large amount of oxidants and proteases that damage tissue when the cells are present in too large numbers (regurgitation, etc.)
Why are the lungs of individuals w/ CF under such great oxidative stress?
What is the effect of this?
Oxygen radicals from:
• host immune response
• pulmonary deterioration
• oxidation of airway proteins
What is bronchiectasis?
Dilation of part of bronchial tree, caused by muscle and elastic tissue damage
What causes the release of large amounts of pro-inflammatory cytokines in the lungs?
Epithelial innate and apative immune cells constantly triggered by:
• infectious agents
What is the role of NF-κB in CF?
(Nuclear factor - κB)
Transcription factor, which is dysregulated in CF
Respiratory epithelium is increasingly pro-inflammatory
What is ceramide, and where is it found?
What is its role in CF?
• Ceramide is a breakdown product of Sphingomyelin
• plasma membrane
• endosomal compartments
Role in CF:
1. Triggers apoptosis & pulmonary inflammation
2. Deposition of DNA from apoptotic cells
What are the triggers of inflammation in the airways in CF?
• CFTR dysfunction
• Unfolded CFTR
• TLR signalling (from microbes)
Describe the role of pulmonary inflammation in CF and pathogens
The pulmonary inflammation may facilitate pathogenesis of organisms:
• Pseudomonas stimulates lipid raft formation
• Lipid rafts contain CFTR and cave-in-1
• Lipid rafts stimulate uptake of the bacterium into epithelial cells
Describe the vicious cycle of pulmonary dysfunction in CF
• Mutation in CFTR gene → viscous mucous
• Viscous mucous → airway obstruction & predisposes infection
• Infection → inflammation
• Inflammation → favours thick mucous production
And the cycle continues...
What can infection, obstruction and inflammation of the airways lead to?
(dilation & damage of bronchi)
• neutrophilic inflammation in and around bronchi
• enlargement of lungs
Which infectious agents are individuals with CF particularly susceptible to?
• S. aureus
• Haemophilus influenza
Describe what happens to lung function over the years in individuals with CF
• Slow decrease in lung function
• Measured as decreased FEV1
NB better outcomes now, as compared to 20 years ago
When does the lung bud first appear during development?
What is being referred to when people say: 'lung function is 80%'?
What is the normal effect of CFTR on ENaC in the lungs?
Normally inhibits ENaC, reducing the Na+ that can come into the epithelial cells
What are the two important antioxidants?
Discuss the interaction between CFTR and antioxidants
CFTR important in Glutathione and Thiocyanate maintenance in epithelial fluid lining
With CFTR mutation, we see increased:
• oxidative stress
• lung inflammation
Which bacteria commonly infect the CF lung?
• P. aeruginosa
• S. aureus
• H. influenzae
What is bad about P. aeruginosa infection in the body?
They form biofilms
Makes it hard for the immune system to clear
Resistant to antibiotics
Is CF obstructive or restrictive?
What happens to FEV1 in CF?
Decreased: not as much volume can be exhaled in the first second as predicted
When performing spirometry, does it take longer or shorter for a person w/ CF to empty their lungs?
What is the tissue origin of the lungs?
Out-pouching of the primitive foregut
When is the embryonic phase?
When does the epithelium of the lungs thin?
When does septation occur?
Alveoar / sacular
When do the lungs start to resemble the lungs in babies and adults?
When do the pneumocytes start to thin?
When does the acinar region develop?
When is the pseudo glandular phase?
When is the sacular phase?
What is this also called?
When do the pneumocytes form?
Describe the connections between the following terms:
• respiratory bronchiole
• alveolar duct
• alveolar sac
Alveolar ducts are tiny ducts that connect the respiratory bronchioles to alveolar sacs, each of which contains a bunch of alveoli (the balls)
When do the alveoli start to develop?
Sacular / alveolar
When is there a decrease in interstitial tissue in development?
Sacular / alveolar
When is the canalicular phase?
How many alveoli in a baby?
1/3rd of the number present in adults
i.e. 100 million
Compare the surface area of the respiratory surface of the lung in babies and adults
Babies: 4 m squared
Adults: 10 m squared
What happens in the post-natal phase?
When is this?
Birth to unknown
Lungs continue to develop after birth, but it is unclear when it finished (at least into the teenage years)