Diffusing Capacity and Limitation
Explain perfusion-limited and diffusion-limited transfer of gases
Define diffusing capacity and its measurement
Describe the physiological factors that alter diffusing capacity
Rate of diffusion of gases is given by Fick's Law:
, where:
- is the pressure gradient across the membrane
- is the area of the membrane
- is the solubility of the substance
- is the thickness of the membrane
- is the molecular weight of the substance
These can be divided into pressure, lung factors, and substance factors:
- Pressure gradient
In the lung, this is a function of:- Partial pressure of the gas in the alveolus
This is affected by:- Atmospheric pressure
- Ventilation
Alveolar hypoventilation will:- Increase PACO2
- Decrease PAO2
- Partial pressure of the gas in blood
This is affected by:- Solubility of the gas in blood
CO2 is ~20 times as soluble as O2 in blood. - Binding of gas to protein:
- Particularly haemoglobin
Affects the rate of uptake of O2 and CO, and is why calculated DLCO is corrected for haemoglobin.- The shape of the oxy-haemoglobin dissociation curve allows a large volume of oxygen to be bound before PaO2 begins to rise substantially.
- Formation of carbamino compounds
- Anaesthetic agents to plasma contents
e.g. albumin, cholesterol.
- Particularly haemoglobin
- Solubility of the gas in blood
- Partial pressure of the gas in the alveolus
- Lung factors
- Surface Area
Affected by:- Parenchyma volume
- Body size
- Pathology
Many lung diseases will reduce surface area for gas exchange.
- V/Q mismatch
Both shunt and dead space reduce the surface area available for gas exchange. - Pulmonary blood volume
Vascular distension and recruitment also affects surface area. Factors affecting pulmonary blood volume include:- Cardiac output
- Increased recruitment of vasculature in high output states
- Decreased recruitment and increased V/Q mismatch in shock states.
- Posture
Increased surface area when supine relative to sitting or standing.
- Cardiac output
- Parenchyma volume
- Thickness
Increasing alveolar-capillary membrane thickness impedes gas exchange. Causes of this include:- Pathology
e.g. Pulmonary oedema and cardiac failure.
- Pathology
- Surface Area
- Substance factors
- Solubility
More soluble substances will diffuse more quickly. - Molecular weight
Smaller substances will diffuse more quickly.
- Solubility
Diffusion and Perfusion Limitation
Limitation refers to what process limits gas uptake into blood:
- Gases which are diffusion limited fail to equilibrate, i.e. the partial pressure of a substance in the alveolus does not equal that in the pulmonary capillary
- e.g. Carbon Monoxide
- Gases which are perfusion limited have equal alveolar and pulmonary capillary partial pressures, so the amount of gas content transferred is dependent on blood flow
- e.g. Oxygen
Oxygen
- Oxygen diffusion takes ~0.25s
- Pulmonary capillary transit time is 0.75s
- Therefore, under normal conditions oxygen is a perfusion limited gas
- However, oxygen may become diffusion limited in certain circumstances:
- Alveolar-capillary barrier disease
Decreases the rate of diffusion.- Decreased surface area
- Increased thickness
- High cardiac output
Decreases pulmonary transit time. - Altitude
Decreases PAO2.
- Alveolar-capillary barrier disease
- Reduced diffusion capacity leads to Type 1 respiratory failure as oxygen is affected to a greater extent than carbon dioxide
Carbon Dioxide
- Carbon dioxide is an exception to these categories and limited by ventilation, rather than diffusion or perfusion.
- This is because CO2 is constantly being produced by the body, and needs to be removed - it therefore moves in the opposite direction to the other gases.
- There is a large amount of carbon dioxide in venous blood, present in various forms:
- Dissolved in plasma (CO2 is 20x more soluble in blood than oxygen)
- Bicarbonate ions (part of the CO2 and pH buffer system)
- Carbamino compounds (largely bound to Hb for carriage to the alveolus)
- This means that although CO2 readily diffuses into the alveolus, the partial pressure in the blood does not change because it is constantly being replenished both from the above stores, and ongoing production by cellular metabolism.
- If equilibrium is reached across the alveolar-capillary membrane, CO2 transfer will stop regardless of speed of diffusion or ongoing perfusion.
- Therefore, the only way to ensure ongoing removal of CO2 from the blood is to clear it from the alveolus i.e. by maintaining alveolar ventilation.
Other Gases
- Carbon monoxide
Diffusion limited due to:- High affinity for haemoglobin
Continual uptake into Hb results in a low partial pressures in blood.
- High affinity for haemoglobin
- Nitrous oxide
Perfusion limited as equilibrium between alveolus and blood is rapidly reached as it is:
- Not bound to haemoglobin
- Relatively insoluble
Diffusion Capacity
- Measurement of the ability of the lung to transfer gases
- Measured as DLCO or diffusing capacity of the lung for carbon monoxide
Carbon monoxide is used as it is a diffusion limited gas. - Process:
- DLCO is decreased in:
- Thickened alveolar-capillary barrier
- Interstitial lung disease
- Reduced surface area
- Emphysema
- PE
- Lobectomy/pneumonectomy
- Thickened alveolar-capillary barrier
- DLCO is increased in:
- Exercise
Recruitment and capillary distension. - Alveolar haemorrhage
Hb present within the lung binds CO. - Asthma (may be normal)
Potentially due to increased apical blood flow. - Obesity (may be normal)
Potentially due to increased cardiac output.
- Exercise
References
- Brandis K. The Physiology Viva: Questions & Answers. 2003.
- Lumb A. Nunn's Applied Respiratory Physiology. 7th Edition. Elsevier. 2010.
- ANZCA March/April 1999
- Yartsev, A. Carbon Dioxide Storage and Transport.