Gas Transfer in the Lung and Lung Function Testing Flashcards
What is the Fick Principle in relation to gas transfer in the lung?
- This says that the volume of gas per unit time which diffuses across a membrane is:
o Proportional to the area of the membrane
o Inversely proportional to the thickness
o Proportional to the difference in partial pressure of the gas on the two sides
o Dependent upon the permeability coefficient for that gas in the membrane (related to the solubility) - Gas transport is maximised in the lung by having a) a large exchange area, b) a thin diffusion membrane, c) a high partial pressure difference, and d) a high permeability coefficient
- According to the Fick principle, when is gas transfer from alveoli to capillaries reduced?
When there is:
o Reduced effective membrane surface area, (eg reduced effective membrane area with pneumonia)
o Decreased diffusion across membrane (eg with pulmonary fibrosis or acute lung injury)
o Decreased partial pressure of oxygen (as in high altitude)
o Collapse of alveoli during expiration (due to lack of surfactant)
o Ventilation-perfusion mismatch (which reduces effective partial pressure difference across membrane)
What commonly causes reduced effective membrane surface area? How does this occur? How does this affect diffusion?
1) Reduced effective membrane surface area; commonly due to lung infections
- In bacterial pneumonia alveoli become inflamed due to the presence of bacterial toxins. Fluid leaks in from the capillaries and can fill up some alveoli, reducing the total alveolar surface area available for gas exchange. Extra fluid lines the walls of other alveoli, reducing the effective diffusion coefficient.
- Remember that macrophages are present in alveoli that phagocytose invading bacteria. They are one of the main defence mechanisms against bacterial lung infection. Conditions that reduce white cell count (e.g. HIV, radiotherapy etc) reduce macrophage numbers and make a person vulnerable to bacterial (or viral) lung disease
How might bacteria in the lungs be dealt with?
- Chemicals in the Surfactant secreted by type 2 pneumocytes help the macrophages engulf and phagocytose bacteria. (see later slide)
- Proteins in surfactant can bind to sugars on the surface of pathogens and thereby opsonize* them. The opsonization attracts the macrophages which can then engulf the bacterium.
- Surfactant degradation or inactivation may contribute to enhanced susceptibility to lung inflammation and infection.
- *Opsonization is the process of coating an antigen on a pathogen with an opsonin molecule, which increases the ability of immune cells to bind to and phagocytose the pathogen
What happens if the macrophages in the lungs cannot cope with the numbers of bacteria?
- If the macrophages cannot cope with the numbers of bacteria, they recruit neutrophils from the blood (by releasing interleukin signalling molecules). (cytokines). The neutrophils enter the alveoli and attack the bacteria, causing pus to form which can further reduce effective membrane area and gas transfer
What can cause decreased diffusion across the alveolar membrane? How does this occur? What effect will it show upon imaging?
- Pulmonary fibrosis occurs when fibroblasts proliferation in the lungs.
- This increases the thickness of the interstitium between the alveolar wall and capillary membranes, greatly reducing gas diffusion and thus gas exchange
- Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. A chest X-ray may or may not be abnormal, but high-resolution CT will frequently demonstrate abnormalities.
What happens at altitude in relation to partial pressure oxygen? What pathologies can this result in?
3) Decreased partial pressure of oxygen at altitude
- Oxygen fraction stays constant but total pressure decreases with height; therefore oxygen partial pressure decreases with height; lower partial pressure of inspired air – lower partial pressure of alveolar air – less saturation of haemoglobin in lungs. Can get altitude sickness if respiration rate not increased
- For oxygen to diffuse into the pulmonary capillary blood there has to be a difference in partial pressure between oxygen in the alveoli and in the pulmonary capillaries.
- At sea level inhaled oxygen is about 20 kPa, but when the gas reaches the alveoli the addition of water vapour has reduced the pressure of oxygen to about 13.3 kPa.
- Blood entering pulmonary capillaries has oxygen levels similar to mixed venous blood, about 5.3 kPa, so the partial pressure difference (the driving force for oxygen uptake) is about 8 kPa.
- When you ascend a mountain, the atmospheric pressure decreases and so does the partial pressure of oxygen.
- At 5000m the atmospheric oxygen partial pressure has halved to 10 kPa and alveolar oxygen will also have halved to about 7 kPa. So the oxygen gradient is now only (7-4.5) 2.5 kPa.
- This drastically reduces the oxygen saturation of the arterial blood resulting in severe hypoxaemia and generalised tissue hypoxia.
- At high altitudes, the low partial pressure of oxygen and resulting hypoxaemia will initially stimulate increased ventilation via the hypoxia detectors in the carotid bodies.
- However, this hypoxia-driven hyperventilation response is antagonised by the more powerful depression of ventilation caused by excess blow off of CO2.
- This CO2 loss causes alkalosis at the central nervous system chemoreceptors, which then prevent the hypoxia driven increase in respiratory drive.
What happens during the collapse of alveoli during expiration? What causes this?
- Without enough surfactant alveoli can collapse and ’stick together’ at expiration; some of these alveoli may not open during inspiration, leading to a reduced surface area for gas exchange.
- Bacterial or viral disease can also affect type 2 pneumocyte function and thus surfactant release
- There are different forms of surfactant (with different proportions of lipoproteins type A, B,C, D) which make with different properties:
o Surfactant containing lipoproteins B &C reduces surface tension and ensures proper lung function.
o Surfactants containing lipoproteins A & D coat bacteria and viruses (opsonization) and help the resident macrophages deal with them
Why does ‘infant respiratory distress syndrome’ occur?
- Developing fetal lungs are unable to synthesize surfactant until late in pregnancy (24-28 weeks)
- Premature babies (before ~28 weeks) may not have enough pulmonary surfactant
- This causes respiratory distress syndrome (IRDS) of the new born; lungs are hard to inflate and some alveoli may fail to open at all during inspiration
- Due to lack of surfactant the baby has to make very strenuous inspiratory efforts in an attempt to overcome the high surface tension and inflate the lungs.
- Treatments for RDS include surfactant replacement therapy and breathing support from a ventilator or nasal continuous positive airway pressure (NCPAP) machine.
Why might ventilation perfusion mismatch occur with chronic lung disease?
5) Ventilation perfusion mismatch a) due to chronic lung disease
- Gas transfer is reduced when there is ventilation/perfusion mismatch. Remember an ideal ventilation/perfusion (V/Q) ratio would be 1 (unity) throughout the lungs.
- Normal lungs have V/Q ratios ranging from >3 at apices to ~0.5 at base.
- Chronic lung disease can reduce compliance of airways; this particularly affects the gas exchange at the base of the lungs as it reduces airflow into alveoli at the base of the lungs and thus reduces V/Q.
- Reduced compliance of airways at base of lungs decreases ventilation at base of lungs and worsens V/Q ratio.
Why might ventilation perfusion mismatch occur with pulmonary arterial constriction?
- ‘Persistent fetal circulation’ is a condition caused by a failure in the systemic circulation and pulmonary circulation to convert from the antenatal circulation pattern to the “normal” pattern at birth. In the fetus the pulmonary capillaries are severely constricted by tonic arteriolar smooth muscle contraction and very little blood flows through the pulmonary artery to the lungs
- Instead, almost all of the output of the right heart shunts into the systemic circulation via the foramen ovale between the two atria and the ductus arteriosus between the pulmonary artery and aorta
- Normally the first breath the neonate takes triggers a dramatic fall in pulmonary vascular resistance and this allows most of the cardiac output from the right heart to now circulate through the lungs; the ductus arteriosus closes naturally in 1-2 hours after the pulmonary circulation is established: the foramen ovale more slowly.
- Persistent fetal circulation is often associated with pulmonary hypertension. Because of this, the condition is also widely known as persistent pulmonary hypertension of the newborn (PPHN).
- For some reason in some neonates the pulmonary vascular smooth muscle does not relax completely after the first breaths and so blood from the right heart stays shunted into the left. This leads to severe hypoxaemia as there is very little lungs perfusion.
- The ductus arteriosus however may start to close. This leads to severe pulmonary hypertension
- PPHN can nowadays be reduced or eliminated by the addition of nitric oxide gas to the inspired gas in the infant ventilator. The nitric oxide relaxes the vascular smooth muscle and normalises pulmonary perfusion
Which tests are used to assess lung function?
- Tests of lung volumes (spirometry)
- Tests of total lung capacity using helium
- Tests of airflow (peak flow meter/vitalograph)
- Tests of V/Q mismatch using isotopes
- Tests of gas transfer (compare PO2 at different sites)
- Tests of challenge by exercise
Why might spirometry be used?
- Spirometry is used to:
o Assess the prognosis of respiratory disease in a patient.
o Assess whether lung disease is present at an early stage, i.e. prior to overt clinical disease.
o Assist in quantifying the severity of airway disease.
o Assess the effect of therapy, such as corticosteroids, bronchodilators
o Delineate risk factors, e.g. the odds of developing future respiratory disease, or operative risks.
o Monitor whether the pattern of lung growth or aging is normal.
How might total lung capacity be measured/calculated?
- TLC, the total volume of the lungs, cannot be measured directly by spirometry.
- It is measured by a dilution method. A fixed volume of a gas mixture which includes helium is inspired, followed by rebreathing the mixture until the helium is evenly distributed in the lung gases. Helium does not get absorbed into the blood, so if we sample the rebreathed gas it will contain a lower concentration of helium than the original inspired gas as it has penetrated the residual volume.
- Let C1 be concentration of helium in inspired gas & V1 volume of inspired gas. Similarly let C2 be concentration in rebreathed gas and V2 the volume (ie V2 = TLC)
Then TLC = V2 = (C1*V1)/C2
How is peak flow measured?
- Simple GP/DIY test: obstruction of airways (eg in asthma) reduces peak flow
- Most useful as serial measurements (each morning & evening)
- Can be used to monitor the effectiveness of treatment
- The peak flow rate assess airway resistance
- The test is useful in patients with obstructive lung disease (e.g. asthma and COPD)
- It is measured by the patient taking a full inspiration and then giving a short sharp blow into the peak flow meter
- The average of three attempts is usually taken
- The peak flow rate in normal adults vary with age and height
