Lecture 10 - Respiratory System and CF Flashcards
Order of branches in the lungs 1) 2) 3) 4) 5) 6) 7) 8)
1) Upper airways
2) Trachaea
3) Bronchi
4) Bronchioles
5) Terminal bronchioles
6) Respiratory bronchioles
7) Alveolar ducts
8) Alveoli
What are acini? (singular: acinus) 1) 2) 3) 4)
1) Respiratory bronchioles
2) Alveolar ducts
3) Alveolar sacs
4) Alveoli
Stages of lung development 1) 2) 3) 4) 5)
1) Embryonic
2) Pseudoglandular
3) Canalicular
4) Sacular/Alveolar
5) Postnatal
Which lung development period is between 0 and 6 weeks of gestation?
Embryonic
Which time is the embryonic period of lung development?
0 to 6 weeks gestation
Which time is the pseudoglandular period of lung development?
6 to 16 weeks gestation
Which stage of lung development is between 6 and 16 weeks development?
Pseudoglandular
Which time is the canalicular period of lung development?
16 to 26 weeks gestation
Which stage of lung development is between 16 and 26 weeks of gestation?
Canalicular
Which time is the sacular/alveolar period of lung development?
26 to 36 weeks gestation
Which stage of lung development is between 26 and 36 weeks of gestation?
Sacular/alveolar
Which stage of lung development is between birth and teenagehood?
Postnatal
When do lung buds first appear?
Day 20-26 (embryonic period)
Which germ layer do the lungs originate from?
Endoderm
What happens in the embryonic period?
1)
2)
3)
1) Lung buds form
2) Ventral outpouching of primitive foregut
3) Endoderm pushes out proximally into surrounding mesoderm
What happens in the pseudoglandualr period?
1)
2)
1) Airways branch until terminal bronchioles
2) This entails 16 divisions of airways
What are terminal bronchioles?
Pre-acinar bronchi
What happens in the canalicular period?
1)
2)
3)
1) Acini form
2) Epithelium thins
3) Pneumocytes form (type I and type II)
What happens in the sacular/alveolar period? 1) 2) 3) 4)
1) Sacules form into alveolar ducts and alveoli
2) Interstitial tissue decreases markedly
3) Septation of alveoli makes more alveoli
4) Walls of sacules become thin
Number of alveoli at birth
10^8
Number of alveoli in adulthood
3 x 10^8
Lung surface area at birth
4M squared
Lung surface in adulthood
10M squared
Functions of the lungs 1) 2) 3) 4) 5) 6) 7)
1) Gas exchange
2) Defence
3) Acid-base balance
4) Heat exchange
5) Water balance
6) Phonation
7) Metabolic
Lung defence mechanisms 1) 2) 3) 4) 5)
1) Upper airway filter
2) Reflexes (sneeze, cough)
3) Mucociliary elevator
4) Alveolar macrophages
5) Surfactant
Airways surface liquid layers
1)
2)
1) Periciliary layer
2) Mucus layer
What coats the mucociliary elevator?
Airways surface liquid
Rate of mucus movement in mucociliary elevator
~1mm/minute
What secrete mucus in airways?
Goblet cells
Function of type I pneumocytes
Make wall of alveoli
Across these O2 is exchanged with alveolar capillaries
Function of type II pneumocytes
Surfactant secretion
How can O2 more easily cross between alveoli and blood?
Fused basal laminae of type I pneumocyte and endothelial wall of alveolar capillary
Lung volume used at rest
Tidal volume
Amount of air that you can breathe in over tidal volume
Inspiratory reserve
Amount of air you can breathe out under tidal volume
Expiratory reserve
What is inspiratory capacity?
Inspiratory reserve + Tidal volume
What is vital capacity?
Inspiratory reserve + Expiratory reserve + Tidal volume
What is residual volume?
Amount of air in lungs that can not be exhaled
What is functional residual capacity?
Expiratory capacity + Residual volume
What is the air that can not be breathed out of the lungs?
Residual volume
What is inspiratory reserve + tidal volume?
Inspiratory capacity
What is inspiratory reserve + expiratory reserve + tidal volume?
Vital capacity
What is expiratory capacity + residual volume?
Functional residual capacity
What is FEV1?
Volume exhaled in 1 second
What is forced vital capacity?
Total volume exhaled in spirometry
What is the total volume exhaled in spirometry?
Forced vital capacity (FVC)
How is lung capacity measured?
With a spirometer
FEV1
Difference between normal flow-volume curve and CF flow-volume curve
With CF, expiratory flow drops very quickly, a airways are narrower.
Takes longer to empty, reinflate lunge
Main cause of morbidity and mortality in CF
Lung infections
Which cell types in the lungs is CFTR expressed on? 1) 2) 3) 4) 5)
1) Ciliated epithelial cells
2) Serous cells of submucosal glands
3) Alveolar type II pneumocytes
4) Alveolar macrophages
5) Neutrophils (role on macrophages and neutrophils not well understood)
Important CFTR function in normal lung
Modulate airway surface liquid
By Cl- secretion, inhibiting Na+ absorption (by inhibiting ENaC)
ASL reabsorption occurs by ENaC actively taking Na+ into epithelial cell, with Cl- moving passively after
When ASL is depleted, CFTR transports Cl- out of epithelial cell and inhibits ENaC from removing Na+ from lungs.
What happens in CF to airway surfactant liquid? 1) 2) 3) 4)
1) Cl- can’t exit type I pneumocytes
2) EnAC Na+ reabsorption isn’t inhibited by CFTR.
3) This results in higher osmotic pressure in pneumocyte
4) Water enters pneumocyte, airway surface liquid is dehydrated, decreases in volume
Result of decreased airways surfactant liquid volume
1)
2)
3)
1) Mucus layer sits on cilia, preventing cilia from beating
2) Mucus isn’t lubricated, so forms plaque on ciliated epithelium
3) Bacteria colonise newly-formed anaerobic environment
How can antimicrobial function be impaired in CF airways?
1)
2)
3)
1) Defective CFTR transport of bicarbonate, pH regulation
2) Inhibits correct function of immune system in airways
3) CFTR might be involved in binding microbes, drawing them into epithelial cells to be killed
Which two important antioxidants does CFTR regulate?
Glutathione
Thiocyanate
Result of impaired CFTR regulation of glutathione and thiocyanate
Glutathione and thiocyanate are important antioxidants
Increases oxidative stress in airways, leading to inflammation
How is an anaerobic environment formed in CF airways?
1)
2)
1) Mucus plaque formed
2) Ciliated epithelium uses more oxygen, as has to work harder
Bacterium which likes to grow in anaerobic parts of CF lungs
Pseudomonas aeruginosa
Which type of inflammation is predominant in CF?
Neutrophilic inflammation
Lung defence against neutrophil-released proteaes
Antiproteases
Overwhelmed with large neutrophil response in CF
Cause of lung inflammation in CF 1) 2) 3) 4) 5)
1) Bacteria grow in anaerobic environments, byproducts include oxygen radicals
2) Oxygen radicals breathed in normally
3) Neutrophils release radical oxygen species, might be overactive in CF
4) Accumulation of abnormally-folded CFTR in cells can lead to apoptosis
5) Abnormal intracellular processes of epithelial cells lead to cell stress, release of cytokines
What is ceramide?
A secondary messenger, a breakdown product of sphingomyelin, which is found in cell membranes, endosomal walls
Excess ceramide leads to apoptosis
What is bronchiectasis?
Dilation of bronchi
What is dilation of bronchi called?
Bronchiectasis
Common pathogen in children with CF
Staph aureus
Common pathogens in adults with CF
Pseudomonas
Burkholderia cepacia
Stenotrophomonas maltophillia
Rising microbe infecting CF lungs
Mycobacteria abcessis
Resistant to many drugs
What does 100% lung function mean?
Mean lung function for a population
Normal range of lung functions
80% - 120% lung function
When does CF lung function begin to deteriorate?
Around teenage years
What is a breakdown product of sphingomyelin, involved in apoptosis?
Ceramide
What information foes FVC give?
Total lung capacity
Doesn’t give information about narrowing of airways
Proportion of CF mortality and morbidity caused by lung disease
90%
Airway surface liquid volume regulation
1) When ASL levels are too high - ENaC actively pumps Na+ into cell. Cl- follows passively.
2) When ASL levels are too low - CFTR inhibits ENaC. Cl- pumped out of cell.
