Alveolar Diffusion Flashcards
Which factors affect the rate of diffusion across a biological membrane?
Fick’s law
◆ The rate of diffusion of a substance across a membrane is directly proportional to the concentration gradient (or partial pressure gradient for gases).
Graham’s law
◆ The rate of diffusion of a substance across a membrane is inversely proportional to the square root of its molecular weight (MW).
Surface area
◆ The rate of diffusion is directly proportional to the surface area of the membrane.
Membrane thickness
◆ The rate of diffusion is inversely proportional to the thickness of the membrane.
Solubility
◆ The rate of diffusion of a substance is directly proportional to its solubility.
Describe the alveolus anatomy that makes it efficient for gas exchange.
❖ A large surface area for diffusion. The lungs contain around 300 million alveoli, which provide a massive 70 m² surface area for gas exchange.
❖ A thin alveolar–capillary barrier, as little as 200 nm in some places.
What are the factors that affect diffusion of substances?
✤ Solubility
✤ Molecular weight
Compare the diffusion of O₂ to the diffusion of CO₂ in the lungs.
The rate of diffusion is affected by:
■ Solubility
■ Molecular weight
✤ O₂ and CO₂ have similar molecular weight;
✤ CO₂ has a higher solubility coefficient than O₂;
✤ This makes the diffusion rate of CO₂ 20 times higher than that of O₂.
In clinical situations where there is a diffusion defect (e.g. in pulmonary fibrosis), O₂ diffusion is more likely to be limited than CO₂ diffusion, resulting in type 1 respiratory failure.
Describe in details the diffusion of O₂ in the lungs.
Oxygen
✤ As O₂ diffuses into the blood (from the alveolar capillaries), most is bound to Hb, but some is dissolved in the plasma.
✤ The O₂ dissolved in the plasma determines its partial pressure PO₂.
✤ As the RBC goes through the pulmonary capillary, diffusion of O₂ into the plasma increases its PO₂, which in turn reduces the pressure gradient across the alveolar–capillary barrier.
✤ An equilibrium is reached between the alveolar and plasma PO₂ after 0.25 s, after which net diffusion ceases.
◉ The inspired gases relevant to anaesthesia (other than O₂) are:
■ N₂O
■ Volatile anaesthetics
■ Carbon monoxide
Describe the rate of diffusion of CO in the lungs.
◉ The inspired gases relevant to anaesthesia (other than O₂) are:
■ N₂O
■ Volatile anaesthetics
■ Carbon monoxide.
CARBON MONOXIDE
✤ MW is low;
✤ More water soluble than O₂;
✤ CO binds to Hb with an affinity 250 times greater than that of O₂ and because of this, only a very small portion of is dissolved in the plasma (it preferes to bind to Hb).
✤ Consequently, the plasma partial pressure of CO (PCO) is very low.
✤ An equilibrium is never reached between alveolar and plasma PCO.
✤ The transfer of CO is diffusion limited because transfer of CO is limited by the rate of diffusion rather than the amount of blood available.
Describe the rate of diffusion of N₂O & volatile anaesthetics in the lungs.
◉ The inspired gases relevant to anaesthesia (other than O₂) are:
■ N₂O
■ Volatile anaesthetics
■ Carbon monoxide
N₂O and volatile anaesthetics
✤ They do not bind to Hb, they are carried in plasma in a dissolved form.
✤ An equilibrium is rapidly reached between the alveolus and the plasma, well before the RBC has traversed the pulmonary capillary.
✤ N₂O reaches equilibrium the most rapidly, within 0.075 s.
✤ N₂O is therefore said to be perfusion limited because more N₂O would diffuse from the alveolus if there were additional blood available.
✤ The volatile anaesthetics behave in a similar manner, but equilibrium is reached slightly later than for N₂O.
✤ N₂O MW is low.
Is the transfer of O₂ perfusion or diffusion limited?
❖ The transfer of O₂ across the alveolar–capillary barrier is perfusion limited;
❖ An equilibrium is reached between the alveolar and capillary PO₂ before the RBC has traversed the pulmonary capillary (like N₂O).
In what situations/scenarios does the transfer of O₂ becomes diffusion limited?
Thickened alveolar–capillary barrier
✤ It decreases the rate of diffusion.
✤ Equilibrium between alveolar and capillary PO₂ is not achieved by the time the RBC reaches the end of the pulmonary capillary, resulting in hypoxaemia.
✤ E.g. pulmonary fibrosis.
Exercise
✤ Cardiac output increases during exercise, which reduces the length of time that an RBC spends in the pulmonary capillary.
✤ Extreme exercise can reduce RBC transit time to as little as 0.25 s (from normal 0.75s).
✤ Patients with a normal alveolar–capillary barrier, are able to reach equilibrium between alveolar and plasma PO₂ in the 0.25 s timeframe (just about).
✤ In patients with disease of the alveolar–capillary barrier, any exercise-induced reduction in RBC transit time results in hypoxaemia (it can’t reach equilibrium even at the end of the RBC pulmonary capillary transit time of 0.75s).
Altitude
✤ At high altitude, the lower barometric pressure PB causes a reduction in alveolar PO₂.
✤ This results in the transfer of O₂ becoming diffusion limited at a lower threshold.
✤ The patient with mild lung disease, where alveolar and plasma PO₂ barely reaches equilibrium at rest at sea level, will develop impaired O₂ diffusion at altitude.
Define what is lung diffusion capacity?
✤ The diffusion capacity of the lung for CO (abbreviated DLCO) is a measurement of the lungs ability to transfer gases.
✤ Is used to diagnose disease of the alveolar–capillary barrier.
✤ It is one of the measurements taken during pulmonary function testing.
✤ CO is a diffusion-limited gas (equilibrium is never reached between alveolar and plasma cause CO prefers Hg).
✤ The test involves a single vital capacity breath of 0.3% CO, which is held for 10s and then exhaled.
✤ The inspired and expired PCO are measured.
✤ The difference is the amount of CO that has diffused across the alveolar–capillary barrier and bound to Hb.
✤ The diffusion capacity is usually corrected for the patient’s Hb concentration, but is also affected by altitude, age and sex.
Describe and give examples of reduced lung diffusion capacity.
Thickened alveolar–capillary barrier
❖ Pulmonary fibrosis and other interstitial lung diseases (chronic);
❖ Pulmonary oedema (acutely).
Reduced surface area for gas exchange
❖ Emphysema;
❖ Pulmonary embolus;
❖ Following pneumonectomy or lobectomy;
❖ In patients who have previously undergone a pneumonectomy or lobectomy, a correction (called the transfer coefficient KCO) is made to account for the loss of alveolar volume so that the diffusion capacity of the remaining alveoli can be assessed.
Describe and give examples of increased lung diffusion capacity.
❖ Exercise following recruitment and distension of pulmonary capillaries.
❖ Pulmonary haemorrhage.
❖ Asthma, but DLCO may also be normal.
❖ Obesity.
Describe the management of a patient with diffusion impairment.
❖ The consequence of impaired alveolar diffusion is hypoxaemia.
❖ Of the 5 factors that govern the rate of diffusion, solubility and MW of O₂ are fixed, but the anaesthetist has a degree of control over the other 3 factors:
➜ Pressure gradient: The reduction in the rate of diffusion due to a thickened alveolar–capillary barrier can be offset by increasing FiO₂, thus increasing the O₂ pressure gradient.
➜ Surface area/thickness of alveolar–capillary membrane: In the specific case of acute pulmonary oedema, raised pulmonary venous pressure results in fluid extravasation into the alveoli and pulmonary interstitium. The alveolar– capillary barrier is thickened and the area available for gas exchange is reduced, both of which reduce the rate of diffusion. In addition to increasing the FiO₂, PEEP can be applied, which:
■ Recruits collapsed alveoli, thus increasing the surface area for diffusion.
■ Increases alveolar pressure to redistribute alveolar oedema, thus reducing the thickness of the alveolar–capillary barrier.
Describe the evaluation lung function tests for lung resection procedure.
✤ As part of the preoperative assessment, it is important to be able to predict a patient’s post-operative lung function.
✤ Post-operative pulmonary function is estimated using a calculation based on the measured preoperative forced expiratory volume in 1s (FEV₁) and DLCO, and then comparing these with predicted values.
✤ By considering both the mechanical abilities of the lung and chest wall (FEV₁) and a gross measure of the alveolar/capillary function (DLCO), patients can be categorised as being at low or high risk of death and post-operative pulmonary complications.
