Respiratory - Alveolar diffusion Flashcards
What is Fick’s law
Fick’s law states that the rate of diffusion across a unit area (such as a surface or membrane) is protportional to the concentration gradient.
What is Graham’s law
Graham’s law states that the rate of diffusion of a substance is inversely proportional to the square root of its molecular weight.
What factors affect the rate of diffusion across a semi-permeable membrane. Rate an equation to summate the relationship of these factors with the rate of diffusion.
- Concentration grad. (Fick’s)
- Square root MW. (Graham’s)
- Surface area
- Membrane thickness
- Solubility
Rate of diffusion = 1 x 3 x 5
_______
2 x 4
Which of the 5 factors that determine rate of diffusion is alterable and why?
- Concentration gradient (Fick’s)
Soulbility and sqaure root MW are inherent properties of the substance itself
Membrane thickness and surface area are inherent properties of the diffusion barrier
Concentration gradient can be altered.
How is the lung alveolus designed for efficient gas exchange. Give numbers to demonstrate this
- Surface area of 300 million alveoli = 70m2
2. Alveolar capillary barrier is 200nm thick
Why is hypoxaemia less likely to be from a diffusion defect versus a V/Q mismatch
RBC transit time: 0.75s
O2 diffusion time: 0.25s
This creates a 3 fold safety factor for diffusion.
Therefore hypoxaemia is more likely to be from a V/Q mismatch
How does the diffusion of O2 and CO2 differ in the lungs.
Give a clinical scenario to demonstrate your answer
O2 and CO2 have similar MWs (32 Da and 40 Da respectively)
CO2 diffusion rate is 20 times higher than O2 because it has a much higher SOLUBILITY coefficient
Pulmonary fibrosis (diffusion defect due to thickened diffusion barrier) –> Low O2 and normal CO2 as CO2 can still diffuse out but O2 inward diffusion is thwarted. So pulmonary fibrosis will lead to type 1 respiratory failure.
Clinically significant hypercapnoea is never caused by impaired diffusion.
Draw the graph and explain the difference between diffusion limited and perfusion limited substances.
Page 41 of Chambers
DIFFUSION LIMITED
- CO binds Hb 250 x more readily than O2
- Almost no CO dissolved, as all bound to Hb
- Therefore diffusing CO never reaches equilibrium with alveolus CO
- It is called diffusion limited because the transfer of CO is said to be limited by the rate of diffusion rather than the amount of blood available.
PERFUSION LIMITED
- N2O (and volatiles) don’t bind to Hb
- N2O and volatiles are relatively insoluble and can only be carried in plasma in a dissolved form, an equilibrium is rapidly reached between alveolus and plasma, well before the the RBC has traversed the pulmonary capillary
- Therefore N2O is perfusion limited because more N2O would dissolve from the alveolus if there was more blood available.
With regards to the N2O / O2 / CO diffusion across the alveolar capillary barrier graph, why does N2O / CO start from 0 and O2 start from higher up on the y axis?
Mixed venous blood already contains O2. But not N2O and not CO, initially.
With regards to the N2O / O2 / CO diffusion across the alveolar capillary barrier graph, why does CO never reach plateau
CO binds with 250 x greater affinity to Hb and hence almost no CO is contained dissolved in plasma. Therefore, an equilibrium is never reached between capillary and alveolus and diffusion continues regardless of perfusion (therefore is diffusion limited)
With regards to the N2O / O2 / CO diffusion across the alveolar capillary barrier graph, why does N2O reach plateau so quickly? How long does N2O take to reach equilibrium between plasma and alveoli
N2O is not bound to Hb and is relatively insoluble in plasma. Therefore, equilibrium between partial pressure of N2O in capillary and alveolus is reached quickly - 0.075s (transit time of RBC is 0.75s). It is therefore considered perfusion limited as it requires more blood to continue diffusing once equilibrium is reached.
Is the transfer of oxygen perfusion or diffusion limited. How do exercise and altitude affect this –> draw a graph to illustrate.
Under normal conditions O2 is perfusion limited (remember the graph). O2 dissolved in plasma reaches an equilibrium with the alveolus after 0.25s at rest. Therefore more blood required for further transfer of O2 from alveolus into capillary (perfusion limited).
EXERCISE
CO increases. During extreme exercise RBC transit time reduced to 0.25 s. If there is a problem with the alveolar-capillary barrier, under this conditions O2 becomes diffusion limited as plasma dissolved O2 will not reach equilibrium with alveoli and hypoxaemia will result.
ALTITUDE
Lower PB and therefore reduced alveolar PO2 –> Transfer of O2 becomes diffusion limited at a lower threshold. (See graph page 42/43 chambers)
What is meant by DLCO
Lung diffusion capacity.
A single vital capacity breath of CO 0.3% is taken.
Inspired and expired Partial Pressure CO are measured.
The difference is the amount of CO that has diffused across the alveolar capillary membrane and bound to Hb.
If decreased DLCO –> reflects disease of the alveolar-capillary barrier
What causes a decreased DLCO
- Thickened alveolar capillary barrier
- CHRONIC: Pulmonary fibrosis/other interstitial lung diseases
- ACUTE: Pulmonary oedema - Reduced Surface Area for gas exchange
- Emphysema
- PE
- Pneumonectomy / lobectomy
What is the transfer co-efficient: Kco
In patient’s with pneumonectomy and lobectomy a correction is made to account for the loss of alveolar volume, so that the diffusion capacity of the remaining alveoli can be assessed. This is called the transfer co-efficient Kco.
