Respiratory #2-4 Flashcards
What are the 5 different stages of lung development?
What type of cell is found in each stage?
- Embryonic (directiculum) → Only progenitor cells
- Pseudoglandular →Progenito cells become Columnar cells
- Canicular → Ciliated cells (1st respiratory epithelial cells) + Columnar cells
- Saccular → Ciliated cells + Columnar cells differentiate into AT1, AT2 and basal cells
- Alveolar → Only AT1, AT2
*Epithelium gradually differentiates
Where do the lungs initially develop from?
Foregut
1. Respiratory diverticulum buds off early on → Gives rise to lungs
Respiratory system shares features that are similar to intestin (both derived from the gut) → Musclar walls in the aways (smooth muscles)
What are the Tracheo-esophageal ridges?
Longitudinal ridges that eventually fuse to separate trachea from esophagus
Failure in splitting keads to communication (fistula) between the 2 structures which requires surgical intervention
Infant would choke on milk if don’t dissociate
What is bronchopulmonary dysplasia?
Can occur in extreme cases of premature birth
- Reduced alveolarization
- Abnormalities of vascular development
What do the right and left lungs develop from?
Lung buds
What are basal cells?
Progenitors of airway epithelium
- Can differentiates into any cells (including cilliated cells) → repair the protective functions of the airway epithelium
What is the importance of type 2 alveolar cells in the alveolar phase and late?
- Become the new progenitor cells
- Replace dammaged AT1 and AT2 cells
- Proliferate in the context of injury (specifically alveolar tissue damage)
- Produce surfactant
What are the main respiratory muscles appart form the diaphragm?
External intercostals → mostly inspiratory in action (pull up the ribs to extend rib cage)
Internal intercostals → mostly expiratory in action
Parasternal area of internal intercostals → inspiration in action
Posterior of external → expiratory in action
*Required for proper diaphragmatic function
What are the main accessory muscles?
- Sternocleidomastoid → elevates the strenum
- Scalenes (anterior, middle, posterior) → elevates and fix upper ribs
- Abdominal muscles (recits abdominis, oblic and transverse) → expiratory in action
- *Tone in abdominal muscles prevents excessive diaphragm shortening
Why is it important to limit diaphragm shortening?
Diaphragm acts just like other skeletal muscles
Respiratory muscle has force-length relationship with optimal length (too much shortening → loss of force)
*By the time the muscle is at 60% of optimal length, lost ability to generate active force
Transdiaphragmatic pressure curve follows force-length relationship —> has optimal length of diaphragm for max Pdi
Velocity-force relationship:
The greater the load, the slower tha ability of the muscle to contract when maximally stimulated (Less load = faster contraction)
How can diaphragm force be assessed?
Placing ballon cathter in the stomach → measures intra-abdominal pressure + one in the lower esophagus → pleural pressure
Difference between both pressures = transdiaphragmatic pressure → declines with increasing lung volume (proves the force-length relationship)
What are the zones of aposition?
Where the diaphragm is in direct contact with the rib cage (no lung between them)
What is the effect of contraction of the diaphragm on the abdominal pressure and the pleural pressure?
Lowers pleural pressure
Increases abdominal pressure → not compressable → abdominal walls move outwards + pushing out the lower rib cage
What happens if diaphragm is only muscle to contract?
Upper part of rib cage would be pulled in (atm pressure > pleural pressure) without action of intercostal
What is bucket handles movement and pump handle movement?
Bucket handle = Contraction of the external intercostals raises the lateral part of the ribs causing a bucket handle motion that increases the transverse diameter of the thorax (rotation)
Pump handle = lateral movement of ribs, when sternum is lifted
How many generation of airways does an airway tree contain?
Up to 23 generations, but path to final alveolar compartement can vary in number
Not perfect symmetrical dichotomous branching
Is the draphragm stimulated unilaterally or bilaterally
Normally stimulated bilaterally, but can be stimulated unilaterally (can breathe normally with 1 side of diaphragm if no lung disease)
What are the characteristics and effects of the airway smooth muscles?
- Narrow the airways when activated
- Same characteristics are skeletal muscles, but slower velocity of contraction and sustained contractions
- Can get active force down to very very short lengths compared to skeletal muscles (not great, because can have closing of the airways)
- have force-length and force-velocity properties
- Innervated by cholinergic (ACh) system (Vagus nerve from CNS)
- Irritant receptors in ariways react and send message through vagues to CNS, get response back
- No dilation innervation (only constricting)
- Spiral around the airways
*No sympathetic innervation to airways (only to vasculature), no nerves dilate airways
How does the length of the diaphragm changes with increasing lung volume?
Diaphragm shortens at higher lung volume
Equilibrium between operating lung volume and operating length of diaphragm
What is the importance of abdominal muscles?
- Role in posture
- Optimizing function of diaphragm → resist descent of the diaphragm during inspiration (relaxation) → facilitate inspiration
- When breathe out → push diaphragm back to resting position
*Maintain length of diaphragm for optimal length
What would hapen to someone with complete paralysis of diaphragm whilst laying down?
Can’t use gravity pull diaphragm down so can’t breathe
Could breathe standing up because gravity pulls diaphragm down and abdominal muscles pushes back
How does the cross-sectional area change across the respiratory system?
Cross-sectional area of repiratory zone/ terminal bronchioles = much greater than Conducting zone
*Exponential curve
Where in the respiraotry system, is the resistance to airflow the greatest?
In larger airways because their cross-sectional area is smaller
What are the layers of the airway tissue?
Surface → deeper
little foldings at the epithelium (with ciliated cells and their contractile apparatus) → basal cells (give rise to new epithelial cells if needed) → connective tissues → muscles
What occurs with airway narrowing?
- More infolded epithelium
- Airway recoil becomes outwards (instead of inwards)
- Alveolar SEPTA → aiway walls can transmit negative pressure from the pleural space into the lungs to pull airways open
- Some airways have cartilage which prevents narrowing
What are the function of lymphatics?
Remove excess fluid to keep alveolar compartements relatively dry
How do airways get nourishment?
Through bronchial circulation → Small shunt of blood that is not oxygenated
Bronchial also helps to heat (conservation of heat) and humidify the inspired air (add water vapour) → add on the way in, take back on the way out (take back the heat which makes water vapour condense)
What is an acinus?
What is the purpose of the holes in alveoli?
Functional unit of the peripheral lung
Holes allow air drift from 1 alveoli to another = Collateral ventilation → increase in number with age
How is the internal surface area of the lung related to the height of a person?
The taller the person, the greater the total surface area of the lungs → not very strong correlation
Other determinants that relate to height that increase surface area
What are the pressure of the systemic and peripheral circulation?
Pulmonary = 25/8 → mean = 15
Systemic = 120/80 → mean = 100
What are lamellar bodies?
Part of the type 2 alveolar cells that produce surfactant
What are the characteristics of type 1 alveolar cells?
Thin, flat cover most of the surface
Responsible for gas exchange
- important to permeability barrier function of alveolar membrane
What are the characteristics of the right ventricle?
- Thinner walled than left ventricle
- Suited to increase in volume
- Unsuited to increase in pressure acutely
- Adapts to pressure chronically by hypertrophy
What are characteristics of lymphatic flow?
- Increased by increased filtration pressure
- Increased by altered pores sizes
- Increased by reduced plasma oncotic pressure
What does the static pressure-volume relationship of the respiratory system show?
S-curve
At extreme volumes → more pressure
What are the different subdivisions of lung volume? (TLC, IC, FRC, IRV, Vt, ERV, RV, VC)
TLC = empty lungs → max insp. = FRC + IC
FRC = empty lungs → quiet exp.
IC = quiet exp. → max insp.
RV = empty lungs → max exp.
ERV = max exp. → quiet exp.
Vt = quiet exp. → quiet insp.
IRV = quiet insp. → max insp.
VC = max exp. → max insp. = ERV + Vt + IRV = TLC - RV
What does the body plethysmograph allow?
Plethysmograph as a device measures flow → in respect to time → gives volume
Measures lung volume changes, changes in the chest wall volume
What are the determinants of static lung volumes? (VC, TLC, RV)
VC is defined by max and min lung volume (TLC - RV)
Determinants of TLC = inspiratory muscle force (neuromusclar diseases) against chest wall and lung recoil forces (emphysema, lung fibrosis)
Determinants of RV = Expiratory muscle force (neuromusclar diseases) against outward recoil of forces of chest wall and airways resistances (obstructive airway diseases, aging)
How is pleural pressure a bit different or similar to measured esophageal pressure?
Inspiration → negative side → pleural pressure = esophageal pressure
Expiratory → positive side → pleural pressure doesn’t quite follow the E.P. line as it can’t go as positive
How can absolute volumes be measured?
With Boyle’s law: PV = kT
PV = (P + ∆P)(V - ∆V) where P = Patm and V = thoracic gas volume at point of occulsion of the airway opening
Patm*Vtg = (Patm + ∆P)(Vtg - ∆V) → Vtg = Patm(∆V/∆P)
How are the elastic properties of the lungs different in inspiration vs expiration?
P-V curve not the same for insp. and exp.
- During inspiration, higher pressure for same volume than during expiration
- During inspiration, as get close to max inspiration → V(y)/P(x) curve flattens at the top
- Linear relationship over good range
Hysteresis = when pathway up and down are not the same
What are the influences of the pressure volume relationship for the respiratory system (chest wall and lungs)
S-shaped
At very low volumes → chest wall outward recoil predominates (Plungs ~ 0, Pw ~ -40 cm H2O)
At very high volumes → The recoil of the lungs predominate (Plungs ~ + 40 cm H2O, Pw ~ + 10 cm H2O)
What happens to abdominal compartement pressure at very low lung volumes?
It becomes negative as the diaphragm is higher up (max ~ -20 cm H2O), ~ 0 cm H2O at 40% of VC
trans-diaphragmatic pressure also becomes negative, ~ 0 cm H2O at 27% of VC (thoracic - abdominal)
What is the effect of transpulmonary pressure on alveolar geometry?
At low transpulmonary pressure → alveolar ducts are narrow, interalveolar wall infolded
Pao = 10 cm H2O, alveolar duct is widened, collagen and elastin fiber system stretched
*Collagen and elastin in inter-alveolar septum controbutes to mechanical properties
Pressure responsible for inflation of lungs = Pleural pressure - alveaolar space pressure
What is a major portion of the elastic recoil of the lungs attributable to?
Air-liquid surface tension
*Seen as lungs inflate a lot easier in saline solution because there is no air-liquid surface
What is the importance of surfactant?
What is it disrupted by?
Reduces surface tension within lungs from 70 dyn/cm → <10 dye/cm
- Polar head (interacts with liquid), non-polar tail
- Principal component = dipalmitoyl-3-sn-phosphatidylcholine
- Surfactant proteins B and C → important for integration in the surface layer
- When surface increase, surfactant is recruited from reservoir, when decrease surfactant is squeezed out
- Small aggregates of surfactant are recycled via endocytosis inside the AT2 cells and re-cycled
Disrupted that cause leaking of plasma proteins into alveolar compartement disrupt surfactant’s function, also damaged by high O2 tensions
What happens to 2 close alveoli without surfactant?
The smaller (greater surface tension) one will recoil and poor into the larger one
Because they all have the same tension T, but different radius
P = 2T/r
Surfactant reduces T to a greater extent in smaller alveoli
What are the 4 major surfactant proteins and their roles?
A → activates macrophages → elicit uterine contractions + cause pro-inflammatory reactions
SPB → organizes into tubular structures that are much more efficient at reducing surface tension (specific deficiency in surfactant B → respiratory distress)
SPC → enhances function of surfactant phospholipids
SPD → important in host defense
What are the effects of prematurity on lungs?
- Lack of surfactant → respiratory distress syndrome (surfactant administration works, only natural surfactant and need presence of SPB and SPC for speading in vivo)
- Inadequately developped alveolar spaces
- Oxygen toxicity + mechanical ventilation → bronchopulmonary dysplasia (arrested dev. of the airways and all tissues)
How are the pressure-volume curves affected by Emphysema and Fibrosis?
Emphysema = loss of recoil → higher TLC, faster increase in volume of lungs with less increase in pressure (steeper slope)
Fibrosis = increased recoil → lower TLC, more increase in pressure needed for same increase in volume
What equations can give us the transpulmonary pressure?
*See the lung as 1 single big compartement from mouth to alveoli
PL = Pao - Ppl = Pfr + Pel = Vt/Cl + RawV’
Pfr = Pao + Pa = pressure drop across the airways = pressure needed to overcome flow resistance
Pel = Pa - Ppl = press difference between alveoli and pleural space (el for elastance on alveoli)
Raw = airway resistance = Pfr/V’ (V’ = flow)
Pel = C(L)/V(T)
What are the relationships between flow, volume and pressures?
Flow = insp → +, exp → -
Volume = increase during insp. decreases during exp.
Pfr = same as flow
Pel = same as volume
P total = offset from Pel curve because of Pfr
P L = P total = Pel + Pfr = Pao - Ppl
What equation measures dynamic lung mechanics? (not elastic work + dynamic work, but similar)
Single compartement model:
P lungs = transpulmonary pressure = ResFlow + Elastance(1/compliance)Volume
What is the equation/variables of passive emptying of the lungs?
Happens as the lungs don’t exactly behave as a homogenous unit
V = V0 e^(-T/τ) where τ = R*C
Different τ → different rates of filling and emptying
- Stiff compartements (lower C) will empty faster
- Lower resistance will lead to faster filling and emptying
*2 alveoli that empty at different rates will join in a common airway and travel at the same speed from that point on
How does dynamic compliance differ at different breathing frequencies?
For healthy subjects → constant ratio between dynamic and static compliance ~ 100% to quite high frequencies
Asthmatic subjects → dynamic compliance falls with increase frequency of breathing (static stays cste) → Heterogenous airway narrowing meaning that in the time avaliable alveoli don’t fill equally/inadequate filling of some airways (can be helped by collateral channels)
Dynamic compliance = difference between transpumonary pressure in inpiration and expiration vs static compliance = pressure at different volumes
What is collateral ventilation?
Prevents areas of lung collapsing when airways are obstructed → alveoli at the end of an airways that is obstructed can still get air and participate in ventilation through other airways
- Increases with age and disease
How is lung volume dependent on resistance?
Closer to TLC, resistance is at its lowest → as lung volume decrease, resistance increases exponentially (mostly after FRC) because airways narrow at lower lung volumes, elastic recoil will pull inwards (no negative pleural pressure to pull outwards)
*Resistive cost higher at lower lung volumes
Airways collapse before reaching RV
That’s why its not advantageous to try to breathe close to RV → takes much more energy
How is work of breathing measured/calculated?
In a fluid system → W = P*V = force over a certain length
Total work = Elastic work + Dynamic work
Dynamic work = needed to overcome resistance of airways
Elastic work = work against elastic recoil of the lungs → helped by outward recoil of the chest wall = space between static pressure-volume curve of lungs and of the chest-wall
What is the effect of Histamine?
Released during allergic reaction → broncho-constrictor
When given to subject → breathing frequency increases → FRC rises gradually → hyperinflation (lungs being pushed to higher volume)
*Increase the work of breathing (elastic work part)
Volume of rib cage increases, Volume of the abdomen (not actual volume, but displacement of abdominal walls) also pushed out
How does work of breathing changes as the lung gets closer to TLC? (During an asthma attack)
- Increase in FRC, higher general lung volume
- Greater swings in pleural pressure for same change in volume → Need greater work
As we get closer to TLC, chest wall starts having positive recoil so elastic work = Pcw + P lungs → much greater
Inspire at much more negative pressures, but expire around the same pressures
What happens to the diaphragm when the abdominal antero-posterior dimension increases?
Diaphragm length is inversly proportional to abdominal volume → increase in abd volume (with asthma for example) → less force from can be generated by diaphragm as it shortens (at 60% of optimal length, can’t generate any force)
Conclusion: maximal transdiaphragmatic pressure declines with shortening of diaphragm
*Force-length curve for skeletal muscle
What physiological circumstances would cause someone to breathe at lower lung volume?
When you lie down, FRC falls, breathe closer to RV. In healthy subject, not a problem
When exercise → breathe out below FRC but mean liung volume is still more elevated (NOT that)
Fibrotic lung → but not physiological
How does the Dynamic pressure-volume loop change with more rapid breathing?
It becomes larger as you need more transpulmonary pressure to overcome the resistance
*Loop around the static pressure-volume curve of the lung
How is work rate optimized?
It is optimized/minimized to different tidal volumes and frequencies at fixed alveolar ventilation and dead space → rate and depth of breathe chosen to minimize the work rate
Total work = Dynamic (resistive, viscous) work + elastic work
Work rate = work/breath * frequency
With high frequency → elastic work goes down and viscous work goes up
Optimized ~ 15 breaths/min
If more shallow breating → dead space takes greater proportion of ventilation → total ventilation must be higher)
If deep breathes → more elastic recoil at higher volumes for each breath (higher muscular cost) → more elastic work
*Optimization seen across different species
How is the work of breathing during asthma?
Work rate increases substantially
- FEV1 falls with more narrow airways
- Different persons experience different degrees of energy expenditure
How does the dynamic collapse of airways lead to limitation of flow?
When pleural pressure becomes very positive → equal pressure point after which aways collapse (pressure goes down gradually from alv → mouth during exp. because of resistance)
This point determines maximal expiratory flow
*Same gradient of pressure between alveolar compartement and choke point no matter the pleural pressure
*Happens even if alveolar pressure increases also in response to higher alveolar pressure
What determines maximal expiratory flow?
- Airway resistance upstream from choke point
- Recoil of the lungs
Dynamic collapse of the lungs → same no matter the pleural pressure
Also the properties of the lungs following this equation:
V max = Area of airways* srqt(A/gas density * transmural pressure difference/change in airway area (airway stiffness))
*Comes down to elastic recoil of the lungs
Choke point = area of airways where smallest expiratory flow is allowed
What are difference between male and femal for lung volume ratios?
Women generally have bigger airway:lung volume ratios → higher predicted FEV1/FVC
What is the typical value of tidal volume?
~ 500 mL
