Surfactant and Resistance Flashcards
what is the elastic properties of the lung & thoracic cage?
If we consider a point when no air flow is occurring:
Distending pressure is equal but opposite to Intrapleural pressure
As when there is no air flow alveolar pressure = 0 (relative to barometric pressure)
Therefore, Distending pressure = Pin (0) - Pout (intrapleural pressure) = - Intrapleural pressure (Ppl)
E.g., Ppl = -0.5 π‘ͺ Distending pressure = 0 - -0.5 = 0.5
Distending pressure is generated by the elastic recoil forces of the lungs and chest wall (both looking to move towards equilibrium volumes so are exerting recoil pressure)
Lung/chest wall volume is determined by the distending pressure that acts across the structure
The Compliance of the structure determines volume for any given distending pressure
what does compliance of the chest wall depend on?
The compliance of the chest wall depends on rigidity and shape of the thoracic cage
Therefore if we distort the rigidity of the thoracic cage or change its shape β> change in chest wall compliance
Most efficient breathing occurs in an upright position, any other change in shape of thoracic cage results in a decrease in chest compliance.
E.g. A decrease in chest wall compliance is caused by arthritis spondylitis, kyphoscoliosis and by spasticity/rigidity of thoracic or abdominal musculature
There are lots of factors that can cause decrease chest wall compliance however there are no diseases associated with an increase in chest wall compliance.
what would difference in lung compliance result in?
A more compliant lung will have greater volume at any distending pressure than a less compliant lung
what is one of the things lung compliance is determined by?
Lung compliance is determined by a number of things:
The elastic properties of lung tissues determine compliance (e.g. collagen, elastic fibres)
When they reach their elastic limit at higher lung volumes the compliance curve flattens out
what is another thing lung compliance is determined by?
explain graph
Surface tension forces due to the air-liquid interface
Dashed line with positive gradient β> compliance around FRC
Line 1 = fluid filled lung
Line 2 = air filled lung
Fluid filled lung: lung surrounded with liquid and being filled with liquid
A Fluid filled lung has much greater compliance than air filled lung - due to removal of air liquid interface - no surface tension
Surface tension: the force found at air-liquid interface trying to collapse the lung
60-75% of the elastic recoil of the lung is caused by surface tension effects
Shaded pink area (includes area under stripes): The work required to inflate an air-filled lung, i.e., work required to both stretch the elastic properties of the lung and work against the surface tension.
Stripey area: work required simply to stretch elastic properties of lung. There is no air liquid interface so no surface tension.
what is surface tension and how does it arise?
Surface tension: the force found at air-liquid interface trying to collapse the lung
How does it arise:
Throughout the liquid water molecules attracted to each other in all directions (shown by small black arrows). Therefore, they are held together.
At the air-liquid interface there are no water molecules in the air to attract water molecules at surface
Therefore the net attractive force of water molecules at surface is inward β> pulling liquid interface inward β> Forms tension (βskinβ)
what causes the alveoli to be pulled inwards?
Lung alveoli are fluid-lined, spherical bubbles (NOT flat surface like a pond!)
Water molecules at the surface of a bubble (i.e. at the air-liquid interface) pull on each other and thus create a tangential component (T) which generates wall tension which pulls the bubble inwards, collapsing the bubble (red arrows)
This generates an internal positive pressure (P) in the gas phase of the bubble.
Therefore, a bubble, with a certain diameter exists at equilibrium (not fully collapsed) when the tangential collapsing force is to equal and opposite to internal positive pressure (P) being generated in the gas phase.
what is Laplaceβs Law (for spherical vessels)?
Pressure inside the bubble is = 2 x wall tension / radius
Therefore if surface tension is constant (which is usually is for the same strucutres) then as radius decreases (bubble gets smaller, collapsing), internal pressure within bubble increases to counteract and keep it inflated
what is alveolar Interdependence?
common misconception?
Different alveoli of different sizes can coexist, due to alveolar inter-dependence
Alveolar interdependence: Each alveolus is surrounded by other alveoli - tendency of one to collapse prevented by tendency of surrounding others not to collapse
Misconception: The reason why different alveoli can co-exist is because smaller bubble have larger pressure, but within lung this is not significant for why bubbles can co-exist
Think of alveoli as βfrothy foamβ (share wall) and not a bunch of grapes (separate walls):
why do calculations using an air-interstitial fluid interface show a very high surface tension?
calculations using an air-interstitial fluid interface show a very high surface tension
This reduces compliance of lungs significantly, making breathing difficult, if not impossible
But breathing is not normally impossible so it canβt just be normal air-interstitial fluid interface in the lungs.
There must be something there that is acting to increase compliance considerably.
There is in fact a chemical in the interstitial fluid called surfactant (surface acting substance)
what is surfactant?
Surfactant: detergent-like substance that acts to greatly reduce surface tension in alveoli
Surface tension of pure interstitial fluid = ~70 mN/m
Surface tension of interstitial fluid with lung surfactant: can drop lower than 2 mN/m (typically ~10x reduction)
So, surfactant increases compliance by lowering surface tension.
what is surfactant made up of?
Surfactant made up of:
35-40% dipalmitoyl phosphatidylcholine (DPPC), a phospholipid
DPPC is the most important phospholipid for reducing surface tension.
30-45% other phospholipids
5-10% protein (SP-A, B, C + D)
Cholesterols (neutral lipids) + trace amounts of other substances
what is surfactant secreted by?
structure of surfactant molecule?
Surfactant secreted by alveolar type II epithelial cells
Structure of a surfactant molecule: glycerol back bone with phosphate and choline residues on one side and palmitate residues (tails) on other side
Palmitate is oily and therefore hydrophobic - when placing surfactant into liquid (alveolar fluid), palmitate residues must stick out of water away from liquid
While hydrophilic elements (charged choline and phosphate) will orientate and place into liquid
Therefore surfactant will always line air-liquid interface due to hydrophobic/hydrophilic components.
how does surfactant prevent surface tension?
Interstitial fluid has high surface tension
Lung-surfactant has detergent effect, decreases alveoli surface tension. This increases lung compliance and therefore reduced the work of breathing
Mechanism of surfactant: Surfactant prevents water molecules from getting to air-liquid interface => prevent such a high surface tension.
what is the area dependent effect of surface tension being altered?
Lung-surfactant can alter its surface tension lowering effect depending on the surface area (red sloped line)
So, in a smaller area you have a greater reduction in surface tension,
Mechanism: Smaller the radius (lower SA) the greater the density of DPPC therefore greater surface tension lowering effect. This is because at a higher density less water molecules can get to air-liquid interface
what is hysteresis of pressure-volume curve for lung?
Hysteresis of pressure-volume curve for lung: if you inflate the lung and measure pressure and volume the curve moves along a different trajectory than when you deflate lung. Particularly if going from Residual volume β TLC and back.
This is due to area-depending effect of lung surfactant.
graph:
Arrow forward = breathing in, Arrow backwards = breathing out.
NB: Saline Inflation (when no air-fluid interface is present) there is no area dependent effect of lung surfactant so no hysteresis
what disease is lung compliance affected by?
how?
Lung compliance is affected by bronchopulmonary diseases
β in compliance (e.g. emphysema) - harder to exhale as there is less elastic recoil
β in compliance (e.g. pulmonary fibrosis/congestion) β stiff lung because tissue is harder to inflate
(in contrast to the chest wall where you can only decrease its compliance)
Both β/β compliance lead to complications β harder to breathe
what is Infant Respiratory Distress Syndrome (IRDS)?
RDS is one of most common cause of β lung compliance
The foetus makes no gas exchange across lungs (gas exchange occurs at placenta)
There the foetus has no air-liquid interface so no need for surfactant.
Surfactant only appears late in gestation, from 25 weeks reaching high concentrations by 32-36 weeks (term = 40 weeks)
It lines the alveolar surface in preparation for air breathing at birth
There are various aetiologies β1000s of infants born with lack of surfactant
Maternal diabetes mellitus - lack of surfactant
Babies born prematurity β> the more premature, the less surfactant
what are the consequences of IRDS?
Alveolar Surface tension is very high
These infants therefore have lungs of low compliance (10x stiffer) and alveoli not stabilised (using surfactant density effect) , with smaller alveoli collapsing as infant expires.
Low compliance also makes Breathing in harder as well β requires a lot of energy
Fibrinous membrane (hyaline membrane) can sometimes forms on alveolar membranes, hindering diffusion of gases across alveolar-capillary membrane
As a result of all of this the infant must expend a lot of energy to inflate lungs, which quickly deflate to low volumes at end inspiration due to stiffness
Infants become increasingly hypoxic, hypercapnic, acidotic and exhausted
how to prevent IRDS?
Assay for phosphatidyl cholines in amniotic fluid before elective induction and caesareans to assess lung maturity β if possible then delay procedure (elective induction/caesarean)
If infant has immature lung, give glucocorticoids to accelerate maturation and endogenous surfactant production.
In infants who develop RDS after birth it is possible to instil surfactant into trachea
All about time: giving enough time for infant to produce their own surfactant (may be necessary to ventilate infant during this time)
what is Adult Respiratory Distress Syndrome (ARDS)?
consequences?
Causes a decrease in lung compliance
It is associated with a large number of disorders, including pneumonia, sepsis, smoke inhalation (fire)
These causes damage to alveolar-capillary interface and therefore damage to alveolar type II cells β can no longer produce surfactant
Similar consequences to IRDS: difficulty to breathe (requires a lot of energy to breathe due to increased surface tension and therefore deceased compliance)
explain respiratory Dynamics β resistance to airflow
Airflow resistance: the pressure difference that is required for a given flow.
The lower the resistance, the lower the pressure difference required for given flow and vice versa
In this context pressure difference is difference between alveolar pressure and barometric pressure
This difference is generated by respiratory muscles
Therefore the lower the airflow resistance the lower work required for a given flow
Higher resistance - more work required to get air to flow at a given rate.
Normal airflow resistance is relatively low: 0.2 kPa.L.s-1
Increased resistance to breathing is most frequent cause of ventilatory impairment (asthma most common cause of increased air resistance)
what would a typical lung compliance curve look like?
Dot at bottom = residual volume
In order to increase the volume of the lungs from dot 1 to dot 2 we need to work to stretch the lung.
If you ask patient to breathe to certain lung volume and then hold their breath (no air movement) we can measure change in distending pressure - indication of work required
Green arrows show work requires to stretch lungs
However, if we do this measurement when air is moving (second curve) instead of two static components, in order to go from dot 1 to dot 2 we require greater work (respiratory muscles have had to work harder)
2nd green line represents extra work required to move air.
This extra work is required to overcome dynamic resistance that is seen when air is moved.
So the work of breathing is into two components
Work required to overcome:
1. Work required to stretch elastic components of lung
2. Extra work required to move air and overcome dynamic resistance
Resistance made up of:
- Airway resistance 80-90% total
This is resistance to flow caused by air molecules rubbing alongside air ways causing friction
Most of work is therefore required to move air against these resistances
- Viscous resistance 10-20% total
Resistance to flow caused by lung tissue friction (movement of lungs themselves)
how do you calculate resistance through airways?
Grey rectangle = airways
ΞP = Barometric pressure vs Alveolar pressure
Air Flow for given delta P dependent on resistance:
what is Poiseuilleβs equation?
L = length of tube
n = viscosity of fluid
8 + Ο are constants
Length (L) is variable, but in terms of airways, pretty constant from breath to breath
Viscosity effectively stays constant
Can alter artificially: giving different gas to breathe e.g. Heliox: helium and oxygen mixture which has lower viscosity so easier to breathe - used in patients who have difficulty in breathing due to increased resistance.
Therefore, you can break down this equation to:
Airway resistance: proportional 1/r4
If you double the radius it will decrease the resistance by 16 (24)
Power relationship - small changes in radius, make large changes to resistance
Therefore, airways diameter will impact on resistance and therefore work of breathing considerably
where is most of the airway resistance?
Trachea has the largest individual cross-sectional area and the respiratory bronchiole a has smaller individual cross-sectional area.
Therefore, using the above equation smaller airways such as bronchioles and alveolar ducts all individually have much higher air way resistance than larger airways like the trachea.
However, the branching of the airways means we do not have only one respiratory bronchiole or a single alveolus therefore we must consider total cross-sectional area
Due to branching the Trachea has a smaller total cross-sectional area whereas the bronchioles and alveoli have a much larger total cross-sectional area (right graph)
Consequently, the vast majority (80%) of airway resistance is highest in the upper airways where the total cross-sectional area is the lowest.
Larynx/pharynx + large airways make up 80% of total airway resistance
Smaller airways: make up 20% of total airway resistance
This mean blocks in small air ways e.g. due to mucus will have lesser effect on air way resistance than blocks in larger airways.
If air ways are narrowed e.g bronchitis, mucus block, asthma (bronchoconstriction) we get higher resistance β more difficulty breathing.
give an example of different effects on resistance?
Breathing through a hosepipe vs breathing through a straw of the same length
Clearly the resistance is greater in the straw as it is much smaller in diameter (cross sectional area) .. but now imaging bundling 200 straws together to make a big tube and breathing through them. They will have a big total surface area and a much smaller resistance now than the hose even though each one is of higher resistance.
what is the significance of airway resistance in clinical settings?
in clinical situations: increases in airway resistance can increase work of breathing to the point where patients are unable to supply sufficient ventilation for metabolic needs.
what are pathological factors increasing airways resistance in the upper airways?
Most frequently caused by intraluminal airways obstruction
Aspiration of foreign material (especially in children)
Regurgitation of gastric contents or blood can also block airways
Coughing may clear obstruction (forced expiration). If not:
Bronchoscopic removal
Heimlich manoeuvre (forcing diaphragm upwards - airways pressure increases distal to obstruction - this causes airflow to move out and clear obstruction.) (done in emergency where medical intervention not possible)
Resistance in upper airways can also be caused by bronchospasm (asthma), mucus secretion (bronchitis) and oedema (liquid formation) by blocking airways.
In patients who are sleep or unconsciousness, severe obstruction may occur from tongue falling back
Recovery position is to account for tongue falling back
what are pathological factors increasing airways resistance in the lower airways?
Increase in airway resistance in Lower airways caused by Chronic Obstructive Pulmonary Disease (COPD)
Low resistance in lower airways means COPD can progress quite far without patient aware, as has little effect on total airway resistance, therefore disease progresses to profound stage before diagnosed (silent zone)
Therapeutic approaches to small airways obstruction relatively poor compared to upper airways obstruction
what is the bronchial diameter controlled by?
Smooth muscle in airways is under control of ANS
- Bronchoconstriction is caused by:
Vagal parasympathetic activity (30% vagal tone to airways at rest, but can be β causing bronchoconstriction)
Vagal parasympathetic activity also induces mucus secretion which also causes β in airway resistance
Local chemical mediators, e.g. histamine, leukotrienes (released in response to inflammatory or infective disease) - Bronchodilation is caused by sympathetic activity:
Activation of Ξ²2-adrenoreceptors by circulating adrenaline or sympathomimetics (drugs)
Non-adrenergic, non-cholinergic (NANC) innervation can cause bronchodilation.
