Respiratory Flashcards
What are the main muscles of inspiration?
- Diaphragm - contracts to force abdominal contents downwards, increasing vertical chest dimension
- External intercostals - bucket handle movement to lift ribs outward and upwards, increasing transverse diameter
What are the accessory muscles of inspiration?
- Scalenes - elevate 1st 2 rib
- SCMs - lift sternum
During quiet breathing, expiration is
passive. The elastic lung and chest wall return to their equilibrium positions after being actively expanded during inspiration.
What are the muscles of active expiration?
- muscles of abdominal wall - RA, IO, EO + TA
- Internal intercostals
What are the antiexpansion forces (resistance to inspiration)?
Elastance
Tissue resistance (pleural sliding)
Airway resistance
What are the key pressures to consider in respiration?
Intraalveolar pressure
Intrapleural pressure
External chest surface pressure (atmospheric)
Transmural pressures - transpulmonary, transthoracic, transrespiratory
How are the transmural pressures calculated?
Transmural pressure = P inside vs P outside. Ie:
P Transpulmonary = Palv - Ppl
P Transthoracic = Ppl - Patm
P Transrespiratory = Palv - Patm
What does it mean for a transmural pressure (e.g. transpulmonary pressure) to be positive or negative?
The transmural pressure determines if the structure is inflating (+ve) or deflating (-ve)
The inflation and deflation P-V curves are different, this is called
Hysteresis - the deflation lung volume is greater than the inflation volume for a given pressure.
What is lung compliance?
Compliance is the volume change of the lung per unit pressure change (the slope of the P-V curve = DV/DP).
At what range of expanding pressures is the lung very compliant?
In the normal breathing range - pressures -5 to -10 cm H2O.
What is the compliance of the normal human lung?
Approx 200 ml/cmH2O. Note that at high expanding pressures the lung is stiffer and compliance is smaller
What pathology reduces lung compliance?
Pulmonary fibrosis
Pulmonary oedema
Atelectasis + increased surface tension in the poorly ventilated lung
What processes increases lung compliance?
Normal aging lung
Emphysema
What is surface tension?
The tension of a surface film of liquid (e.g. H20 in the alveoli), caused by the attraction of the surface layer to the bulk of the fluid (unopposed downwards + inwards attraction), which tends to minimise surface area.
What is the collapsing pressure?
It is a measure of the tendency of an alveolus to collapse, proportional to the surface tension and inversely proportional to radius (P= 2T/r)
What does the collapsing pressure equation imply about alveolar stability?
The alveolar system is inherently unstable
- the collapsing pressure is related to the radius, the smaller alveoli will have larger pressure - and tend to empty into larger alveoli
- hence the larger alveoli will be overventilated, and smaller alveoli underventilated
What problems does surface tension create?
1) Tendency of collapse
2) Alveoli become unequal
3) Alveoli become wet (high T pulls transudate)
How is surfactant produced?
It is made + stored in Type 2 pneumocytes as lamillar bodies, and then secreted as tubular myelin.
What is surfactant?
Dipalmitoyl phosphatidylchloline - A molecule with hydrophobic (2x palmitoyl) + hydrophilic (phosphate, choline + apoproteins) regions.
How does surfactant decrease surface tension?
The DPPC molecules insert themselves into the H20 layer, therefore disrupting the unopposed H20 attractions (intermolecular forces - hydrogen bonding) that lead to surface tension.
What is the special defence function of the A+D apoproteins?
A+D apoproteins of the DPPC molecule are opsonins - they bind bacteria to facilitate phagocytosis by macrophages
What are the physiological advantages of surfactant?
By decreasing surface tension, surfactant:
- increases lung compliance => reduces WOB
- Stabilises alveoli (decreases collapsing pressure (P=2T/r) and reduces tendency of smaller alveoli to empty into larger)
- Keeps alveoli dry (prevents transudation of capillary fluid)
What are the consequences of loss of surfactant? And what is a pathological example of this?
- stiff lungs (low compliance)
- atelectasis
- oedema (transudate into alveoli)
Occurs in neonatal Respiratory Distress Syndrome
What is alveolar interdependence?
Interdependence refers to the support offered to lung units by those surrounding them, which resists collapse of individual units.
CO2 + O2 TRANSPORT
-
What volume of O2 is delivered to the tissues per minute?
250ml/min of O2
What volume of CO2 is produced by tissues per minute?
200ml/min of CO2
GAS DIFFUSION
All gases move across the alveolar wall (blood-gas barrier) by passive diffusion
What is Fick’s Law?
Fick’s Law states that the rate of transfer of a gas through a sheet of tissue is:
proportional to the tissue area, partial pressure gradient and solubility of the gas
inversely proportional to tissue thickness and molecular weight of the gas
What are some key features and measurements of the blood-gas interface?
Extremely thin - 0.2-0.3 um
Enormous surface area - 50-100m2 - by having 500 million alveoli
So thin that large increases in capillary pressure can damage barrier.
What layers does O2 cross when diffusing across the blood-gas barrier from alveolar gas to Hb?
surfactant, epithelial cell, interstitium, endothelial cell, plasma, RBC membrane
What are some key features of pulmonary capillaries?
They form a dense network in the alveolar walls.
Capillary diameter is 7-10 um, just enough for RBC
RBC spends 0.75 s in the capillaries
What are key features of the conducting zone?
- Consists of trachea, bronchi, bronchioles to terminal bronchioles (first 16 generations).
- cartilage in walls
= anatomic dead space = 150ml - blood supply from bronchial circulation (mere fraction of pulmonary circulation)
- convectional airflow
What are key features of the respiratory zone?
- Consists of respiratory bronchioles, alveolar ducts + alveolar sacs (each unit called acinus), gens 17-23
- smooth muscle walls
- 2.5-3L volume
- Gas movement by diffusion
What has been shown about regional differences in ventilation?
In subjects who inhale radioactive xenon gas, ventilation per unit volume -
lower> upper lung (standing)
posterior > anterior (supine)
Explain the helium dilution technique
FRC and RV cannot be measured with simple spirometry - to measure FRC, subject is connected to spirometer with known Conc of helium (insoluble in blood).
After some breaths, helium concentration in lung + spirometer equilibrate.
What is alveolar ventilation equation and it’s importance?
Alveolar ventilation VA = VCO2/PCO2 x K
In normal subjects PACO2 + PaCO2 are identical, so arterial can be used.
VA is inversely proportional to PCO2 - i.e. halving the alveolar ventilation with double PCO2 (assuming constant CO2 production)
Which gases are diffusion or perfusion limited?
CO - diffusion limited
NO - perfusion limited
O2 - perfusion limited under normal conditions (diffusion limited at altitude)
What is the Hb molecule?
Hb is a tetramer - each monomer is made up of:
a protoporhyrin ring with central ferrous iron (Fe2+)
globin protein tail
Describe the 3 main types of haemoglobin
HbA - 2 alpha + 2 Beta chains (Adult)
HbA2 - 2 alpha + 2 delta chains (normal variant present in low levels in adults)
HbF - 2 alpha + 2 gamma (fetal, replaced over first 6 months of life)
What is methemoglobin?
Normal HbA can have its ferrous ion (Fe2+) oxidised to ferric form (methemoglobin) by various drugs/chemicals - nitrites, sulphonamides, acetanilide.
Congenital deficiency of methemoglobin reductase - imparts oxygen binding/release to tissues
How is oxygen carried in the blood?
In 2 ways - dissolved O2 + Hb bound
Dissolved O2 obeys Henry law, which means that..
the amount dissolved is proportional to partial pressure.
For each mmHg PO2, there is 0.003ml O2/100ml blood.
So normal arterial blood contains how much dissolved O2?
At PaO2 100: 0.003 x 100 = 0.3ml O2/100ml blood
How much O2 can 1g Hb bind?
1.39 ml / g
What is the oxygen carrying capacity of Hb in 100ml arterial blood?
If a person has Hb concentration 15 g/100ml
15 x 1.39 = 20.85 ml O2 / 100ml.
(One can then add 0.3 ml dissolved O2 to calculate total O2 concentration in 100ml blood)
In general, O2 concentration in the blood is given by..
(1.39 x Hb x Sat/100) + (0.003 x PO2)
Compare the normal O2 saturations + volumes, in arterial + mixed venous blood.
What is the minute delivery of O2 to tissues (resting state)?
Arterial P02 100 mmHg - 97.5% - approx 20ml O2
Venous PO2 40 mmHg - 75% - approx 15ml O2
So 5ml O2 is delivered to tissues / 100ml blood.
If resting CO is 5L/min, 50 x 5 = 250ml O2/min
What is positive cooperativity?
O2 binding at the Fe2+ site, increases affinity of next site for O2
What are the key anchor points on the Oxygen dissociation curve?
PO2 100 mmHg => SO2 97%
PO2 40 mmHg => SO2 75%
P50 = 27 mmHg => SO2 50% (useful measure of L or R shift)
What are the physiological advantages of the shape of the oxygen dissociation curve?
The flat upper portion - falls in PO2 have little effect on SO2
The steep lower portion - peripheral tissues can withdraw large amounts of O2 for only small drop in PO2
What factors shift the oxygen dissociation curve to the right?
Right shift (reduced Hb-O2 affinity) is caused by: Increased H+, PCO2, temperature and 2,3-DPG in RBC - enhances O2 delivery to metabolically active tissues
What factors shift the oxygen dissociation curve to the left?
Left shift (increased Hb-O2 affinity) is caused by: Decreased 2,3-DPG, HbF
What factors alter production of 2,3-DPG?
2-3-DPG is produced by RBC in chronic hypoxia - e.g. high altitudes, chronic lung diseaseWIt’s levels are low in stored blood for transfusions
What is the effect of carbon monoxide on the oxygen dissociation curve?
CO has 240 x more affinity than O2 for Hb - so even a small amount of CO will bind up significant amounts of Hb in the blood.
COHb (carboxyhemoglobin) is not able to carry O2 - hence it will shift the curve downwards
Hb concentration and PO2 will remain normal, but SO2 will be significantly reduced.
COHb also impairs oxygen unloading, so shifts curve left
How do anaemia and polycythemia affect the curve?
Anaemia - decreased Hb = decreased O2 carrying capacity, curve shifted down
Polycythemia - increased Hb = increased O2 capacity, curve shifted upward
What is the Bohr effect?
The Bohr effect describes the rightward shift of the oxygen dissociation curve with increased PCO2 - mostly attributable to the rise in H+ - acidic Hb has lower affinity for O2 (favours O2 dissociation + release to tissues)
How is CO2 carried in the blood?
In 3 forms -
1) Dissolved CO2 (24 x more soluble than O2, 0.067 ml/100ml/mmHg, also obeys Henry law)
2) Bicarbonate HCO3-
3) Carbamino compounds (CarbaminoHb)
