Video 2 3D model of the trachea, bronchi and bronchioles. (Please note, this video has no audio.)
This is a “moving” picture, giving a rotating, stereoscopic-effect view of the lungs, bronchi and vertebral column.First view shows two pink lungs, viewed from the front. Between the lungs at their tops is the trachea (in yellow-grey) with stiffening cartilaginous rings. About one third the way down the lungs the trachea branches into the right and left bronchi. The vertebral column (in grey) lies behind the respiratory organs. The illustration rotates clockwise.Subsequent views show the lungs from the right and left sides, with the trachea entering between the lungs, and the vertebral column lying behind the respiratory organs.In a final view the lungs are removed to show the trachea, bronchi and the bronchi branching (in what would be within the lungs) in a ramifying system of bronchioles with smaller and smaller branches.The lungs are organised into lobes (the left lung comprises two lobes and the right lung has three lobes). Two thin membranes, the visceral and parietal pleura, cover the lungs and keep them attached to the thoracic wall. The base of each lung is concave and rests on the diaphragm (more on that in Section 1.2), whereas the heart sits within the cardiac impressions, or grooves, in each lung (Figure 1, repeated). Because they act as a conduit for air to move into and out of the lungs, the nasal passages, pharynx, larynx, bronchi and bronchioles are collectively referred to as the conduction zone of the respiratory system. Air then passes into progressively smaller structures deep in the lungs where gas exchange actually takes place in the respiratory zone, which you will explore in the next section. 1.1.3 Respiratory zoneThe terminal bronchioles each divide a further seven times into respiratory bronchioles, then alveolar ducts and finally into alveolar sacs (alveoli; singular, alveolus) that contain holes in their walls called alveolar pores (Figure 3).Similar to other organs in the body, the organisation of the bronchioles and alveoli allows a large surface area of cells to be contained within the tight space of the thoracic (chest) cavity. This large respiratory surface, which is about 140 m2 in the adult human (roughly the size of a tennis court), enhances the lungs’ capacity to exchange CO2 for O2. This exchange occurs in the respiratory bronchioles, alveolar ducts and alveoli, which collectively form the respiratory zones deep in the lungs.Alveoli are surrounded by a network of pulmonary capillaries that carry the blood (Video 3). Deoxygenated, CO2-rich blood coming into the lungs from the heart exchanges CO2 for O2 by diffusion, and oxygenated blood then leaves the lungs, returning to the heart to be pumped around the body. The walls of an alveolus and a pulmonary capillary are each only one cell thick, which allows diffusion of O2 and CO2 to occur very quickly (Figure 4).Because haemoglobin, the molecule that carries O2 in the blood (explored further in Section 4.2), changes colour when bound by O2, oxygenated blood is often depicted as bright red, whereas deoxygenated blood is shown as blue in colour. This course doesn't explore how blood circulates around the body, but it is important to note that the lungs differ from other organs in that deoxygenated blood is carried to the lungs via arterioles (and larger arteries), whereas oxygenated blood leaves the lungs along venules (and larger veins).
Video 3 Exchange of CO2 and O2 carried by blood in the pulmonary capillaries within the alveoli of the lungs. (Please note, this video has no audio.)
This is a “moving” picture, giving a rotating, stereoscopic-effect view of a respiratory bronchus, an alveolar sac and associated pulmonary capillaries. The figure shows a horizontal pink tube, a terminal bronchiole, with a respiratory bronchiole leading down from it into an alveolar sac (looking like a bunch of grapes), each alveolus being spherical. Over one side of the alveolar sacs are branching, bright red capillaries and on the other side (seen as the figure rotates clockwise) are bright blue capillaries.Activity 1 Ordering the air flowAllow about 5 minutesTo test your understanding so far, order the steps involved in the flow of air from the conduction zone through to the respiration zone.12345In the next section, you will explore the muscles that are involved in the expansion and contraction of the lungs. 1.2 Muscles of ventilationThe expansion and contraction of the lungs is controlled mechanically by the diaphragm and the intercostal muscles (Figure 1, repeated).The diaphragm is a dome-shaped muscle that sits underneath the lungs and separates the thoracic cavity from the abdominal cavity. It is innervated by the phrenic nerve, which originates in the medullary respiratory centre in the medulla of the brain.The intercostal muscles are located in the ribcage. They receive neuronal inputs from intercostal nerves that arise from the thoracic nerves of the spinal cord.The bronchi and bronchioles are also surrounded by smooth muscle cells that contract and dilate to regulate the amount of air that passes down to the alveoli.Activity 2 Diaphragm and intercostal muscles Allow about 20 minutesPart 1To explore the location and function of the diaphragm and intercostal muscles, take a look at the anatomical information and diagrams on this site (open the links in a new tab/window so you can easily return to this page):DiaphragmIntercostal musclesPart 2Now try matching each of these statements with the correct muscles.diaphragmexternal intercostal musclesinternal intercostal musclesinnermost intercostal muscles1.3 Mechanics of inhalation and expirationMovement of the diaphragm and intercostal muscles acts to expand and decrease the size of the thoracic cavity, creating pressure gradients that draw air into and force air out of the lungs, as described in Video 4.
Video 4 Mechanics of inhalation and expiration.
NARRATOR During inhalation, the diaphragm contracts, causing it to flatten out and move downwards. At the same time, the ribs are moved upwards and outwards by contraction of the external intercostal muscles. Contraction of the diaphragm and the external intercostal muscles increases the volume within the ribcage so that there is a larger area for the lungs to expand into. This creates a pressure gradient within the thoracic cavity that draws air into the lungs.Expiration is generally a passive event brought about by relaxation of the diaphragm and external intercostal muscles. The ribcage, diaphragm and lung tissue itself return by elastic recoil to their original pre-inspiratory positions. The consequent retraction of the chest wall forces air out of the lungs. Forced expiration is mainly achieved by contraction of the internal intercostal muscles, aided to some extent by contraction of the abdominal muscles.Most of the time, you will be unaware of the contraction and relaxation of the muscles that control respiration. They become much more noticeable when you cough or develop a bout of hiccups. In fact, hiccups are caused by a spasm of the diaphragm and intercostal muscles in response to increased activity of the phrenic nerve and vagus nerve (which innervates the muscles of the abdomen). The spasms cause the floor of the thoracic cavity to drop suddenly, which pulls air quickly and forcefully into the airways. Movement of the air past the closed vocal cords creates the characteristic ‘hic’ sound.Activity 3 Lung in a bottleAllow about 1 hourYou can explore the relationship between movement of the diaphragm and lung volume directly by making your own ‘lung in a bottle’ as shown in Video 5.
Video 5 ‘Lung in a bottle’ experiment.
CHERYL HAWKES Today I’m going to show you how you can make your own lung in a bottle to better understand how changes in pressure drive air into and out of the lungs. For this activity, you will need a clear plastic bottle, about 500 millilitres, two balloons, some Blu-Tack with a hole in the middle, two small straws, or one large straw, and one pair of scissors. The first thing to do is to cut your bottle in half with the scissors, which can be a little bit fiddly, so I’ve made one already. And we’re going to use the top of it to make our model. And next, take one of your balloons and cut the top of it off. I’m going to take this part of the balloon and wrap it around the base of the bottle. Next, we’re going to take the second balloon and insert it into the bottle. And then wrap the lip of the balloon around the top of the bottle. Then, you take the two straws and cut them about a quarter of the way down. Next, we’ll insert the straws into the hole in the Blu-Tack, and put both of these into the mouth of the balloon. And then squeeze the Blu-Tack down over the straws and the lip of the bottle just to make sure that you seal off the bottle completely. So here we have the model of the lung in the bottle where the straws represent the trachea, the balloon inside represents the lungs, the plastic represents the ribs and intercostal muscles, and the balloon at the bottom represents the diaphragm. Watch what happens when I pull up and down on the diaphragm-- you see that the balloon lung inside inflates as I pull down on the diaphragm. And that’s because when you do that the air pressure inside the lung is lower than the air pressure outside. And so the air flows down into the lungs. When you press the diaphragm inwards, the balloon collapses, because the pressure inside the ribs is higher than the pressure outside. And this drives the air out of the lungs. So there you have it, your very own model of a lung in a bottle. According to the video, what factors are responsible for the inflation and deflation of the balloon ‘lung’ inside the bottle? Pulling down on the blue balloon ‘diaphragm’ caused the air pressure in the ribcage to drop lower than the air pressure in the atmosphere. This drove air to flow down its pressure gradient into the balloon, causing it to inflate. Pressing up on the diaphragm increased the air pressure in the ribcage, driving air out of the balloon lung and causing it to collapse.1.4 Non-respiratory functionsThe respiratory system also performs important non-respiratory functions, for example:Vocalisation including speech and singing. The two bands of elastic tissue that lie across the opening of the larynx, called the vocal cords, can be stretched and positioned into different shapes by the laryngeal muscles. As air is passed over the vocal folds, they vibrate to produce characteristic patterns of sound.Detection of smells from airborne chemicals.Water loss and heat elimination. Inspired atmospheric air can be humidified and warmed by the respiratory airways; this is essential to prevent the alveolar membranes from drying out, which would significantly reduce diffusion of O2 and CO2.Facilitation of blood flow around the body. During inspiration, there is a fall in pressure in the chest cavity, which reduces the resistance of blood vessels. In a similar way, respiratory movements also aid the movement of lymph through the lymphatic system.Defence against foreign particulates or airborne infectious diseases via nasal hair and cilia lining the airways, and mechanisms including coughing and sneezing.2 Factors affecting pulmonary ventilation The previous section outlined the anatomical structures that are involved in ventilation. In this section, you will examine the factors that regulate pulmonary ventilation, including pressure gradients, surface tension, airway resistance and compliance of the lungs. 2.1 Atmospheric pressureIf you have recently taken a flight on a commercial airline, you will be familiar with the instructions that are given in the event of a change in cabin pressure, such as in Video 6 below.
Video 6 An Open University airline safety video.
FLIGHT ATTENDANTWelcome to OpenAir flight 299, en route to Milton Keynes. Please pay attention to the safety features of this Airbus 320, which are shown on the flight card in the seat pocket in front of you. In the event that the airplane loses cabin pressure, oxygen masks will drop down automatically. Remain seated with your seat belt fastened, pull down on the mask, and place it over your nose, using the elastic band to secure it to your head. Continue to breathe normally as oxygen will follow automatically into the bag. Remember to secure your own mask before assisting someone else. Thank you for choosing OpenAir. We wish you a safe and pleasant flight. These safety measures highlight the importance of pressures for gas exchange in the lungs. To understand this relationship, it is helpful to use Boyle’s law, which states that at a constant temperature (k), an increase in pressure (P) causes a proportional decrease in volume (V). Watch Boyle’s law in action in Video 7 below. (Make sure to open the link in a new window/tab so you can easily navigate back to this page.)Link to Video 7 – The effect of increasing pressure on volume.Question 2 Increasing pressureBy how much did the volume of air in the cylinder decrease when the surrounding water pressure increased from 1 bar to 2 bar? it did not changeby ¼by ½by ¾As the pressure increased by a factor of 2, the volume of the air decreased by ½, from 1 litre to 0.5 litre.In physiology, the unit of pressure is conventionally measured as millimetres (mm) of mercury (Hg). ‘Millimetres of mercury’ (mmHg) refers to the height of a column of mercury attached to an instrument that detects pressure (e.g. a sphygmomanometer). Other units of pressure, such as that used in Video 7, include bar, pounds per square inch (psi) and pascals (Pa). All units of pressure can be interconverted, so 1 bar = 14.5 psi, 1 psi = 51.7 mmHg and 1 mmHg = 133 Pa.At sea level, the atmospheric pressure (i.e. the pressure exerted by the gases in the Earth’s atmosphere) is about 760 mmHg. During inhalation, the volume of the lungs increases and the pressure inside the lungs decreases below that of atmospheric pressure. This creates a pressure gradient that draws air into the lungs. During exhalation, the lungs return to their original size, pressure in the lungs rises compared with the atmospheric pressure and air moves out.Question 3 Boyle's lawBoyle's law is described by the following formula:PV = k.Part 1How would you rewrite the formula to calculate pressure (P)?P = k/V. To calculate pressure (P), divide the constant (k) by the volume (V).Part 2i) If k = 1, what will be the pressure of the gases if the volume of the lungs is 6 litres?0.167 mmHg6 mmHg16 mmHgPart 3ii) If k = 1, what will be the pressure if the volume is 3 litres?0.333 mmHg3 mmHg13 mmHgPart 4Is the pressure in the lungs higher during exhalation or inhalation?ExhalationInhalationNeither, it is constantAs the volume of the lungs shrinks during exhalation, the pressure in the lungs increases above that of atmospheric pressure and air moves out of the lungs down the pressure gradient.If you are unfamiliar with rearranging equations you might find our Mathematics for science and technology course helpful for brushing up.Returning to the example of the aeroplane, the atmospheric pressure at cruising altitude (e.g. 243 mmHg at 30 000 feet or 9100 metres) is much lower than that at sea level (760 mmHg). If you were exposed to that same pressure as a passenger, the pressure in your lungs would be greater than that of the atmosphere, and you would be unable to draw a breath.In the next section, you will learn how differences in pressures of gases in the atmosphere versus pressures of those gases in the lungs also drive O2 and CO2 exchange.2.2 Partial pressurePressure is an important factor in O2 and CO2 exchange in the alveoli. The pressure of each individual gas in the atmosphere is described as its partial pressure.Partial pressure is calculated by multiplying the percentage of the particular gas in the atmosphere by the total atmospheric pressure. For example, O2 accounts for about 21% of the Earth’s atmosphere so the partial pressure of O2 (PO2) in the atmosphere is 0.21 × 760 mmHg = 160 mmHg. CO2 is present only in trace amounts, so the partial pressure of CO2 (PCO2) in the atmosphere is roughly 0.3 mmHg.Question 4 NitrogenNitrogen (N2) comprises 78% of the Earth’s atmosphere. What is the partial pressure of nitrogen (PN2)?The PN2 in the atmosphere is 0.78 × 760 mmHg = 593 mmHg.The difference in PO2 and PCO2 between fresh air and the blood drives the diffusion of O2 and CO2 down their respective concentration gradients, as described in Video 8.
Video 8 PO2 and PCO2 in lung and tissues.
SPEAKERAir that enters the lungs contains both oxygen and carbon dioxide that are present in the atmosphere. The partial pressure of oxygen as it enters the body, abbreviated as PO2, is around 160 millimetres of mercury. Within the moist environment of the alveoli, the PO2 decreases to 104 millimetres of mercury. The partial pressure of carbon dioxide as it enters the body, abbreviated as PCO2, is around 0.3 millimetres of mercury. The carbon dioxide delivered to the lungs from the blood raises the PCO2 in the alveoli to about 40 millimetres of mercury. De-oxygenated blood from the systemic tissues is carried to the lungs by the pulmonary arteries and has a PO2 of 40 and a PCO2 of 45 millimetres of mercury. As the blood enters the alveoli, the higher PO2 in the lungs drives oxygen shown in red out of the alveoli and into the blood. At the same time, the slightly higher PCO2 in the blood drives carbon dioxide, shown in blue, out of the blood and into the alveoli. Because this diffusion is fast, the PO2 and PCO2 of the blood rapidly matches the PO2 and the PCO2 of the air in the alveoli, at which point there is no more net movement of oxygen and carbon dioxide. Oxygenated blood is now carried by the pulmonary veins to the heart where it will be pumped out to the systemic tissues. Within the tissues, metabolically active cells consume oxygen and produce carbon dioxide. This results in a PO2 of about 20 millimetres of mercury and a PCO2 of about 46 millimetres of mercury in the cells. Within the surrounding tissue fluid, the PO2 is approximately 40, and the PCO2 is around 45 millimetres of mercury. Because the PO2 is highest in the blood, oxygen will diffuse from the blood into the tissue fluid and then into the cells. In parallel, carbon dioxide, whose partial pressure is highest in the cells, will diffuse down its pressure gradient from the cells into the tissue fluid and then into the blood. Again, this process occurs quickly so blood that is carried by the systemic veins has the same PO2 and PCO2 as that in the tissue fluid. And at this point, there is no more net movement of oxygen and carbon dioxide. De-oxygenated blood is now returned to the heart to be pumped out to the lungs, and the cycle of oxygen and carbon dioxide exchange between the tissues, blood and lungs begins again. Activity 4 O2 movementAllow about 5 minutes2.3 Decompression sicknessIf you think back to William Trubridge and his free-diving record in the Introduction, you will recall that he swam up from a depth of 102 metres in just over 2 minutes, a rate of 51 m min−1, without suffering any ill effects on his return to the surface. By contrast, scuba divers are advised not to ascend faster than 9 m min−1 to avoid developing decompression sickness (‘the bends’). This discrepancy between free-divers and scuba divers lies in the differences in partial pressures of gases that are inhaled under atmospheric pressure and under compression. When you breathe from a scuba tank, the air has the same pressure as the pressure of water at that depth. The pressure of water is much higher than air; for example, at 20 m below the surface of the water, the pressure exerted by water on the body is about three times that experienced on dry land. The high pressure can cause some of the N2 gas in the air to dissolve into the blood. As the diver swims back up to the surface, the PN2 in the blood is higher than in the surrounding water, so N2 will be released from the blood and into the alveoli to be exhaled. If the change in pressure happens too quickly, the N2 will not have time to be exhaled and instead will form air bubbles (similar to what happens when you open a shaken can of fizzy drink). These bubbles can cause severe pain in joints and muscles and in extreme cases, death due to embolism. Free-divers experience the same effects of PN2 as scuba divers at deep depths. However, because free-divers are not breathing pressurised air as they dive, their lungs actually get compressed (down to a quarter of their original size) by the high pressure of the water. As the divers ascend, their lungs will slowly expand back to their original volume.Question 5 Pressure in the lungsAccording to Boyle’s law, what will happen to the pressure in the lungs as the free-divers ascend (see Section 2.1)it will increaseit will stay the sameit will decreaseIt will decrease. According to Boyle’s law, P = k/V, so as the volume gets bigger, the pressure gets smaller.So, as the divers return to the surface, the PN2 in the lungs decreases relative to the PN2 in the blood and N2 diffuses into the alveoli, thereby decreasing the chances that it will form bubbles in the tissue.2.4 Surface tensionIn the previous section, you saw how partial pressure gradients drive the exchange of O2 and CO2 between the blood and the alveoli. Diffusion of the gases at this air–liquid interface is facilitated by a thin layer of water that coats the inner surface of the alveoli. Condensation of the water vapour that is exhaled when you breathe out is the reason why you ‘see’ your breath in cold weather. Individual molecules of water (H2O) bind together because hydrogen and oxygen atoms are strongly attracted to each other. This is why your hair sticks together when it’s wet. This force is called hydrogen bonding.Because hydrogen bonds are quite strong, when water molecules come into contact with each other, they will be held together tightly. This tight packing creates a surface tension in the water that forces it to adopt the smallest shape possible (e.g. a droplet) (Figure 6).However, because the alveoli are round in shape, the surface tension that holds the water molecules together also puts an inward pressure on the inside of the alveolus (Figure 7). As you have just learnt, if the pressure in the alveolus is higher than the atmospheric pressure, air from the atmosphere will not enter and the alveolus will collapse (a medical condition called atelectasis). How does the lung combat the surface tension of water to ensure that the alveoli can expand with each breath? Cells within the alveoli secrete surfactant, a substance that attaches to the water molecules and prevents them from interacting with each other. This reduces the surface tension in the alveolus to near-zero levels. This effect is nicely demonstrated in Video 9. Why not try this experiment yourself at home?
Video 9 Surface tension broken by surfactant.
SPEAKERWhen powder is sprinkled onto a beaker of green coloured water, it floats because of the surface tension of the water. A squirt of dish detergent acts as a surfactant, breaking the surface tension of the water and allowing the powder to sink.Surfactant also serves to prevent the collapse of the alveoli of newborn babies when they take their first breaths. Premature babies born before their surfactant production system is fully functional suffer from respiratory distress syndrome (RDS). Surface tension in the lungs of these babies is high and many alveoli fail to expand. Failure to produce enough surfactant may also be a problem in adult life; for example, surfactant production in the lungs of smokers is greatly reduced, increasing the likelihood of breathing difficulties compared to non-smokers.2.5 Compliance and airway resistanceThe ease with which the lungs and pleura expand and contract based on changes in pressure is called compliance. Low lung compliance means that the lungs and alveoli are ‘stiff’, so a higher-than-normal pressure gradient is needed to get the lungs to expand and contract. It can result from insufficient amounts of surfactant or fibrosis of the lungs due to prolonged inhalation of small particles such as asbestos or coal (e.g. black lung) (Figure 8). High compliance results when the lungs are too pliable and move in response to small changes in pressure. This makes exhalation difficult because the elastic recoil of the lungs (i.e. their ability to ‘snap back’ after inhalation) is decreased. High lung compliance is a characteristic of chronic obstructive pulmonary disease (COPD), a general term for a collection of diseases that are associated with lung damage, such as emphysema and chronic bronchitis, which are often associated with smoking (Figure 9).Activity 5 Comparing tissuesAllow about 10 minutesCompare the tissue sections in Figure 9. List the differences you observe between:1. the healthy lung versus the smoker's lungThe tissue from the healthy lung is uniform and pale in colour throughout. The lung from the smoker is bigger and contains large holes and has black-brown discolourations (probably due to tar and other particulates contained in cigarette smoke).2. the healthy alveoli versus the COPD alveoliThe alveoli in the healthy lung are well defined and interconnected. The alveoli in the lung affected by COPD have incomplete and thinner walls, do not make as many connections with other alveoli and have larger air spaces that reduce the respiratory surface.Pulmonary ventilation is also affected by the resistance of the airways to the flow of air. This resistance is caused by the friction that is generated when the air passes along the structures in the conduction and respiratory zones. Because the airways are made up of a series of tubes, resistance is largely affected by the diameter of the trachea, bronchi and bronchioles. Resistance is inversely proportional to radius, so structures with a small diameter have a higher resistance.Question 6 Airflow resistanceIs the airflow resistance in a bronchiole higher or lower than in a bronchus?higherlowerneither, they are the sameThe radius of a bronchiole is smaller than that of a bronchus. A smaller radius results in higher resistance. Therefore, the resistance to airflow is higher in the bronchiole compared with the bronchus.During an asthma attack, the airway resistance increases because the bronchial smooth muscle cells contract and reduce the diameter of the bronchi and bronchioles. This results in the characteristic wheezing, coughing and shortness of breath. Fast-acting reliever inhalers release drugs that relax the smooth muscle cells and thereby increase airflow.In the next section, you will see how lung capacity and function are measured and used as a guide for overall lung health.3 Lung function Changes in the compliance and resistance of the lungs can affect the capacity of the lungs to hold and exchange air. Lung capacity is calculated from the volume of air that is exchanged during normal and forceful breathing. The volumes that are used to calculate total lung capacity are described in Video 10.
Video 10 Calculating lung capacity.
SPEAKERLung capacity is calculated from the volume of air that is exchanged during normal and forceful breathing. Resting tidal volume refers to the amount of air entering or leaving the lungs in a single normal breath, and is about half a litre in adults. If you take a deep breath in, the extra volume of air inspired is called the inspiratory reserve volume. Likewise, if you breathe out for as long as you can after a normal intake of breath, the extra volume breathed out is the expiratory reserve volume.The average inspiratory volume for an adult is about 2 to 3 litres, while the expiratory reserve volume is about 1 litre. There is always a small amount of air left in the lungs in addition to the expiratory reserve volume. And this is known as the residual volume.Vital capacity is the sum of the tidal, inspiratory and expiratory volumes. Total lung capacity is the sum of all the volumes, including the residual volume. Total lung capacity represents the maximum amount of air that the lungs can hold.Activity 6 Lung capacityAllow about 10 minutesPart 1Match the volume with the corresponding definition: extra volume breathed out during forceful exhalationextra volume breathed in during forceful inhalationamount of air left in the lungs in addition to the expiratory reserve volumeamount of air entering or leaving the lungs in a single resting breathPart 2Which of the volumes are NOT used to calculate the vital capacity of the lungs? Select all that apply.tidal volumeinspiratory reserve volumeresidual volumeCorrect. The vital capacity is the sum of the tidal volume, inspiratory reserve volume and expiratory reserve volume. expiratory reserve volume3.1 SpirometryLung function can be measured using spirometry. A typical test involves blowing out into a spirometer as hard as possible until the lungs are empty (Figure 10). The forced vital capacity (FVC) is calculated as the total volume of air that can be forcefully blown out. Peak expiratory flow (PEF) measures the maximum speed at which air is forcefully expired (litres per second). The forced expiratory volume 1 (FEV1) is the amount of air that is forcibly blown out within the first second of the test. Plotting the FVC and PEF values generates a spirograph similar to the one shown in Video 7. The FEV1/FVC ratio (also calculated as a percentage) is used to evaluate lung function. In healthy individuals, the FEV1/FVC ratio is approximately 0.8, meaning that 80% of total volume of air is blown out within the first second.It is important to note that normal lung function is dependent on an individual’s age, height, sex, ethnicity and general fitness. An example of the predicted FEV1/FVC ratios for particular groups of men and women is shown in Table 1.
Table 1 Predicted FEV1/FVC ratios for asymptomatic, lifelong non-smoker Caucasian men and women over the lifespan.
FEV1/FVC (%) Male
Age
20
25
30
35
40
45
50
55
60
65
70
75
80
All heights
83.9
82.9
81.9
80.8
79.8
78.8
77.7
76.7
75.7
74.6
73.6
72.6
71.5
FEV1/FVC (%) Female
Age
20
25
30
35
40
45
50
55
60
65
70
75
80
All heights
86.6
85.5
84.4
83.4
82.3
81.2
80.2
79.1
78.1
77.0
75.9
74.9
73.8
Question 7 Lung function across agesLooking at Table 1, what happens to lung function with age in both men and women? It stays the same across all ages.It increases with age.It decreases with age.Correct. Lung function, as measured by the FEV1/FVC percentage, decreases with age in both men and women. 3.2 Lung function impairmentWhen lung function is impaired, the PEF, FEV1, FVC and FEV1/FEC values can be used to help determine the cause of the dysfunction; for example, decreased lung volume due to fibrosis or increased airway resistance due to asthma.Activity 7 Spirometry experimentAllow about 2 hoursIn this activity, you will use the spirometer application in the Open Science Laboratory to measure changes in FEV1/FEC over time between smokers and non-smokers. Here's the link to the application – open it in a new window or tab, so you can return to this page easily.Link to Spirometer applicationBefore you begin collecting data, watch the video in the Introduction tab of the spirometer to familiarise yourself with the application.Research studies that look at relationships between different groups of people can be categorised into cross-sectional or longitudinal studies. Cross-sectional studies compare different groups of people at one moment in time. Longitudinal studies analyse the same group of people across different points in time.Now go to the Spirometer tab in the application and set the following parameters:age: 20maleheight: 180 cmnon-smoker Start the measurement and record the output of the FEV1, FVC and FEV1/FVC (%) using the ‘Record data’ button. Repeat this measurement three times, remembering to record the data each time.Repeat the data collection for the same male individual at ages 40 and 80. Repeat both measurements three times, remembering to record the data each time.Then select the same parameters for age, sex and height, but choose ‘smoker’. This group smoked one pack of 20 cigarettes each day from the age of 20. Collect data for three ages – 20, 40 and 80 – repeating and recording the measurement three times.Select the ‘Export data’ button then copy and paste the results into a spreadsheet program such as Excel.Determine the mean (average) of the three values that you collected of FEV1/FVC (%) at each age for the non-smoker and smoker conditions.Plot a computer-generated x–y graph showing the mean FEV1/FVC (%) of the smoker and non-smoker at 20, 40 and 80 years of age. Make sure to plot this in chronological order.4 Gas exchangeIn this section, you will examine the chemical changes that underlie exchange of O2 and CO2 between peripheral tissues and the lungs. You will also learn about genetic mutations of haemoglobin and how the body senses and responds to changes in O2 and CO2 levels to maintain homeostasis.4.1 O2 and CO2 transport in the bloodYou've seen how gradients between PO2 and PCO2 drive gas exchange in the alveoli. But how are these gases carried in the blood? Small amounts of O2 (~0.3%) and CO2 (~3%) dissolve directly into the plasma. However, such concentrations are not sufficient to fulfil the metabolic demands of the body. The main transport of O2 and CO2 in the blood is mediated via haemoglobin molecules and bicarbonate ions, respectively.4.2 HaemoglobinMost O2 is carried in the blood by erythrocytes (red blood cells) which contain haemoglobin (Hb). In adults, Hb is a protein formed of four polypeptide chains, called globins – there are two alpha and two beta chains (Figure 11). Attached to the interior of each globin chain is a small non-protein structure known as a haem group. The haem group has at its centre an iron ion (Fe2+) that binds to one O2 molecule. As there are four globin chains and four haem groups, each with one Fe2+, one Hb molecule can carry four O2 molecules. When O2 is bound to Hb, the Hb is said to be oxygenated and the complex formed is called oxyhaemoglobin. Oxygenation occurs where there is a plentiful supply of O2; that is, in the capillaries surrounding the alveoli of the lungs.O2 binding to Hb is governed by positive cooperativity, meaning that once one haem group binds O2, it becomes progressively easier for the other haem groups to also bind O2. This ensures that the Hb molecule can become quickly saturated (i.e. with four O2 molecules bound). Oxygen saturation levels (‘sats’) are used by doctors to detect respiratory distress or illness.Binding of O2 to Hb is reversible, meaning that when oxyhaemoglobin reaches the capillaries within the tissues, where O2 is being consumed and the PO2 is low, the O2 is released and diffuses into the tissues. Hb that is not bound to O2 is termed deoxyhaemoglobin.Question 8 Pulmonary arteriesWhich form of Hb is predominant in the blood carried by the pulmonary arteries? (see Section 1.1.3)oxyhaemoglobindeoxyhaemoglobinPulmonary arteries carry blood coming from the peripheral organs into the lungs where CO2 will be exchanged for O2, so they carry CO2-rich blood. Therefore, the predominant form of Hb in the pulmonary arteries will be deoxyhaemoglobin.The binding and dissociation of O2 to and from haemoglobin is dependent on the PO2. This is not surprising, because as you saw in Section 2.2, differences in partial pressures between tissue capillaries and pulmonary capillaries drive the exchange of O2 and CO2. However, if you look at the oxygen–haemoglobin dissociation curve in Activity 8, you will see that O2 binding to haemoglobin is not a linear relationship. Rather, the amount of Hb bound to O2 over a range of PO2 has a sigmoidal ‘S’-shaped curve.Activity 8 Oxygen–haemoglobin dissociation curveAllow about 5 minutesTake a look at this dissociation curve, then place the marker as directed and click ‘Enter answer’. If you place it correctly, one more question will then be posed to you.Line graph showing percent of haemoglobin (Hb) saturated with oxygen (on a scale from 0% – 100%) on the vertical axis, and PO2 in mmHg from 0 – 100 mmHg on the horizontal axis.The oxygen dissociation curve is shown as a red line starting from the origin for both axes, rising to give a 70% Hb saturation at PO2 of 40 mmHg; the curve then rises less steeply, almost to plateau at about 95% Hb saturation at PO2 of about 90 mm Hg.At 30 mmHg an arrow notes that there is a low PO2 in tissue: less oxygen is attached to the Hb; at 78 mmHg an arrow notes that there is a high PO2 in the alveoli: lots of oxygen is attached to the Hb.The student is invited to drag a marker to the point in the curve where 50% of the Hb is saturated with O2.4.2.1 Influencing the curveA number of biological factors influence the oxygen–haemoglobin dissociation curve and shift it to the right or left. These factors are summarised in the following video.The term ‘affinity’ refers to the strength of binding between two particles or proteins. Low affinity means that the binding is weak and the particles can be easily separated. High affinity means that the binding is strong. In the context of Hb and O2, low affinity means that the O2 binds weakly to the Hb and is therefore easily transferred to the tissues.
Video 11 Factors influencing the oxygen–haemoglobin dissociation curve.
SPEAKERWhere the partial pressure of oxygen is high, such as in the pulmonary capillaries of the lungs, oxygen binds readily to haemoglobin. Here, the haemoglobin is almost 100% saturated, meaning that each molecule of haemoglobin contains four molecules of oxygen. As oxygenated haemoglobin moves through the tissue capillaries, it encounters decreasing partial pressures of oxygen and the affinity, or strength of binding between haemoglobin and oxygen, decreases. As a result, the percentage of haemoglobin saturated with oxygen falls as oxygen diffuses into the tissues. The partial pressure of oxygen, at which there is 50% saturation of haemoglobin, is called the P50, and under resting conditions is about 26.7 millimetres of mercury. The affinity of haemoglobin for oxygen increases and decreases to maintain homeostatic delivery of oxygen to cells depending on several biological factors. For example, during exercise, muscle cells become more active and produce more carbon dioxide and heat which, in turn, increase the acidity and content of the haemoglobin protein 2,3-diphosphoglyceric acid, or DPG. The active cells will also be using more oxygen. So the partial pressure of oxygen in the cells will drop. To meet the increased demands for oxygen, the affinity of haemoglobin for oxygen will decrease as the partial pressure of oxygen drops. This effectively shifts the P50 to the right, and means that haemoglobin becomes desaturated more quickly. Notice in this example how under conditions of increased exercise the same partial pressure of oxygen results in less haemoglobin saturation, as oxygen diffuses more easily into the active cells. Conversely, when levels of carbon dioxide are low, such as in the capillaries of the lungs, the affinity of haemoglobin for oxygen increases. This effectively shifts the P50 to the left, and means that oxygen diffusing from the alveoli binds tightly to the haemoglobin entering the lungs. This helps to keep oxygen bound to haemoglobin as it leaves the lungs to be carried to the peripheral tissues. An easy way to remember how the oxygen–haemoglobin dissociation curve changes based on metabolic demand is to use the mnemonic CADET face right, meaning that increasing the levels of CO2, Acidity 2,3-DPG, exercise and temperature will shift the P50 to the right, and vice versa. Question 9 Biological factorsHaving watched Video 11, note down the biological factors that affect the affinity of Hb binding of O2.CO2acidity2,3-DPGexercisetemperature4.3 BicarbonateIn the previous section, you saw how the affinity of Hb for O2 decreases in the presence of elevated CO2 and acidity. This is known as the Bohr effect. This is due to the chemical reaction that takes place between CO2 and water (H2O) to generate bicarbonate (HCO3−) and protons (H+). This reaction is represented by the equation:H_2O + CO_2 \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3 \ ^-In chemistry, the ⇌ arrow represents a reversible reaction, meaning it can go in the right or the left direction. In this case, adding more CO2 will push the reaction to the right and generate more H+ and HCO3− ions. H+ ions decrease the pH of a solution (make it more acidic) whereas HCO3− ions increase the pH and make it more basic.The reversible nature of this reaction is critical in allowing the body to transport CO2 from the tissues and be exhaled in the lungs. This process is detailed in Video 12.
Video 12 Bicarbonate buffering.
SPEAKERTissue cells that are metabolically active produce carbon dioxide that diffuses into erythrocytes in the systemic capillaries. Carbon dioxide combines with water in the erythrocytes to produce a weak acid called carbonic acid. This reaction is facilitated by the enzyme carbonic anhydrase, which acts to speed up the reaction. Carbonic acid dissociates into a bicarbonate ion and a proton. The proton binds to haemoglobin, forming protonated haemoglobin, or HHb. The bicarbonate ion diffuses down its concentration gradient into the blood, taking along its negative charge. To balance the charge in the erythrocyte, chloride ions, which are also negatively charged, move into the erythrocytes from the blood in a process known as the chloride shift. The reverse chemical reaction takes place in erythrocytes that move into the capillaries of the lungs. Bicarbonate from the blood moves into the erythrocyte and chloride leaves to balance the charge. Haemoglobin donates a proton, which combines with bicarbonate ions to produce carbonic acid. Carbonic anhydrase catalyses the conversion of carbonic acid into carbon dioxide and water, allowing the reaction to take place quickly. Carbon dioxide then diffuses down its concentration gradient across the alveolar walls and is exhaled. In Video 12, you saw that protons (H+) generated during bicarbonate buffering of CO2 bind to Hb in the erythrocytes to form protonated haemoglobin (HbH+). This binding decreases the affinity of Hb for O2, thereby facilitating O2 diffusion into tissues, as described by the following equation:HbO_2 + H^+ \rightleftharpoons HbH^+ + O_2At the same time, CO2 that has not been converted into HCO3− (~30% of total CO2 in the blood) binds with high affinity to deoxyhaemoglobin to form carbaminohaemoglobin (HbCO2). This complex is then carried to the lungs (Figure 12).In the alveoli, binding of O2 to HbH+ results in the release of free H+ ions.Question 10 Higher H+In what direction will the higher concentration of H+ push the equilibrium reaction?H_2O + CO_2 \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3 \ ^-left, towards increased CO2 productionright, towards HCO3− productionneither, the reaction will stay in equilibriumThe answer is left. It will help drive the diffusion of CO2 out of the blood and into the alveoli to be exhaled.In parallel, carbaminohaemoglobin loses its affinity for CO2 as it becomes reoxygenated. Collectively, these actions increase the PCO2 at the alveoli. The phenomenon by which O2 influences CO2 concentrations is known as the Haldane effect.The capacity of the blood to carry O2 is also greatly reduced by carbon monoxide (CO), a gas emitted by car exhausts and faulty gas appliances. CO competes with O2 for binding to Hb. Because the affinity of Hb for CO is higher than its affinity for O2, CO molecules will bind preferentially and irreversibly to form carboxyhaemoglobin (HbCO), which is cherry red in colour. Inhaling CO will therefore progressively reduce the amount of Hb available to bind O2 and lead to CO poisoning. If the source of CO is not removed, death could result due to the total lack of oxygen (asphyxiation). 5 Inherited disorders of haemoglobin In the previous section, you saw that erythrocytes and the haemoglobin they contain play a crucial role in mediating exchange of both O2 and CO2 between the tissues and the lungs. This section will use two examples, sickle cell anaemia and thalassaemia, to illustrate how genetic disorders of haemoglobin can affect gas transport and exchange in the body. 5.1 Sickle cell anaemiaSickle cell anaemia gets its name from the abnormal shape of the erythrocytes, which resemble that of an old farming tool, the sickle (Figure 13). This shape is due to a single nucleotide substitution (A to T) that converts a glutamic acid codon (GAG) into a valine codon (GUG) in the beta chains of Hb.Activity 9 RNA codon wheelAllow about 15 minutesTake a look at this interactive RNA codon wheel. If you click on an amino acid, the diagram will highlight the corresponding nucleotides. You can view some further information and chemical structures for each amino acid. When you’ve done this, use the diagram to answer the question underneath.Three concentric circles. The innermost divided into four equal sectors: G, U, A and C. Outside this circle is a second circle, with sixteen sectors, divided four times into U, C, A and G, for each of the inner circle U, C, A and G respectively. The outermost circle indicates pairs, triplets or quartets of nucleotides: outside of the circles each pair or trio or quartet of nucleotides in the outermost circle is matched with the name of an amino-acid.Which nucleotide substitution would still result in a functional Hb protein? GAG → GCGIncorrect. Substitution of A by C will produce the codon GCG which codes for the amino acid alanine.GAG → GAACorrect. Both GAG and GAA are codons for glutamic acid. Therefore, substitution of G by A will still produce a functional Hb protein.GAG → CAGIncorrect. Substitution of G by C will produce the codon CAG which codes for the amino acid glutamine.Sickle Hb is denoted as HbS. Because glutamic acid is negatively charged, these amino acids would normally repel each other and help the Hb retain its shape. However, these repulsive forces are absent in the HbS because valine is uncharged.HbS is able to bind O2 normally in the lungs and carry it to the tissues. However, as the HbS becomes deoxygenated, the valine amino acids are exposed and start to bind to each other, forming long chains of deoxyHbS. These chains distort the cell and cause it to bend out of shape. As more and more deoxyHbS molecules come in contact with each other, they can result in the formation of a chain of sickled erythrocytes, which clump together and get stuck in the capillaries (Figure 14).Sickled erythrocytes that return to the alveoli will regain their biconcave disc shape as they once again become oxygenated. Note that erythrocytes carrying normal Hb maintain this biconcave shape regardless of their O2 saturation levels.The repeated episodes of polymerisation and depolymerisation of HbS as it travels between the lungs and tissues damages both the haemoglobin molecules and the erythrocyte itself, making it rigid and unable to move through the small-diameter capillaries.Amplified many times, blockage of the capillaries can produce tissue hypoxia (i.e. low levels of oxygen), resulting in tissue pain and damage. In addition, the sickled erythrocytes are more fragile and die on average after 20 days in circulation, compared with normal erythrocytes that live for 120 days. Loss of erythrocytes leads to the anaemia (low red blood cell count) of sickle cell disease.Symptoms of sickle cell anaemia include episodes of pain (called sickle cell crises) in tissues and bones, swelling of hands and feet, frequent infections, delayed growth and problems with vision. In addition, chronic pulmonary complications are common in individuals with sickle cell disease, including asthma, pulmonary fibrosis, decreased FEV1 values and sleep apnoea (which is further explored later in the course).Sickle cell anaemia is a recessive disorder, meaning that in order for an individual to develop the disease, they must inherit two HbS alleles.5.2 ThalassaemiaThalassaemias are a group of inherited autosomal recessive disorders that cause anaemia because of the decreased or absent synthesis of a globin chain (Muncie and Campbell, 2009). Alpha thalassaemia is the result of either deficient or absent production of the alpha globin chain, which is then replaced by extra beta globin chains. Production of the alpha globin protein is slightly more complicated because it is controlled by two genes, both located on chromosome 16. This means that disease susceptibility is dependent on the inheritance pattern of four alleles – two inherited from the mother and two from the father. Alpha thalassaemia is usually due to the deletion of one of these alleles and the severity of the disease corresponds to the number of deletions:one deletion is silent and asymptomatictwo deletions result in mild anaemiathree deletions cause haemoglobin H disease and moderate to severe anaemiafour deletions cause alpha thalassaemia major, a fatal condition.Activity 10 Inheritance pattern of alpha thalassaemia Allow about 20 minutesIn this activity, you will predict the phenotype and pattern of inheritance of alpha globin genes in a family affected by alpha thalassaemia. Click below to reach the full activity.Beta thalassaemia results from deficient or absent production of the beta globin chains, leading to excess alpha chains in the Hb molecules (Figure 15).Unlike alpha thalassaemia, beta thalassaemia is usually due to a point mutation (more than 200 of which have been identified to date) in the gene that codes for beta globin. Again, the degree of disease symptomology is dependent on how many beta globin chains are functional. Beta thalassaemia minor is asymptomatic whereas beta thalassaemia major causes growth retardation, skeletal abnormalities and jaundice, and requires lifelong blood transfusions to treat.The overall effect of either alpha or beta thalassaemia is haemolysis, the rupture and destruction of the erythrocytes. Because of this, people with thalassaemia are at risk of developing pulmonary hypertension, a higher than normal pressure in the arteries that carry blood to and from the lungs. This can cause dizziness, shortness of breath and damage to the heart.Question 11 Hb mutationsWhy do you think Hb mutations that cause potentially fatal anaemias continue to exist in the human genome?The rates of both sickle cell anaemia and thalassaemias are higher in people of African, Southeast Asian and Mediterranean descent. It is not a coincidence that these are also regions where the malaria parasite is highly prevalent. Heterozygous carriers of the HbS gene or thalassaemia mutations are less likely to be infected with the Falciparum malaria parasite than people with the normal copies of those genes. Malaria can cause serious illness and over one million people die from the infection every year. Therefore, mutations in Hb lead to a trade-off between increased risk of anaemia and decreased risk of death from malaria. Malaria is a good example of how parasites (and other infectious organisms) exert evolutionary pressure on the human genome to adopt multiple polymorphisms that protect against severe disease. 6 Control of respirationGenerally, respiration is an involuntary, automatic event. You are probably not aware it is happening unless you exert voluntary control over it by holding your breath, or breathing deeply. The rate and depth of your respiration adjusts automatically according to the metabolic needs of the tissues in the body. For example, athletes will breathe much more quickly and deeply during bouts of exercise to accommodate increased aerobic activity of their muscles, as discussed from 2:13 onwards in this video about Olympic rowing. (Make sure to open the link in a new window/tab so you can easily navigate back to this page.)Link to Video 13 – Anatomy of a rower.How does the body sense and respond to changes in metabolic rate? This function is mediated by peripheral chemoreceptors in the blood vessels and heart, and central chemoreceptors in the brain that detect changes in O2 and CO2 levels in the blood. Although changes in the partial pressures of both gases are involved in the regulation of respiration, alteration in PCO2 is the principal driver of respiration rate in humans.6.1 Central chemoreceptorsChanges in PCO2, and therefore in pH, are detected largely by chemoreceptors within the respiratory centres of the brain (Figure 16). During increased metabolic activity, such as exercise, the PCO2 in the arterial blood increases.Question 12 Increased exerciseWhat happens to the P50 (the PO2 at which 50% of Hb molecules are saturated with O2) of the oxygen–haemoglobin dissociation curve during increased exercise? (see Section 4.2)it increasesit decreasesit stays the sameIncreasing exercise will shift the oxygen–haemoglobin dissociation curve to the right, so the P50 will increase.As CO2-rich blood reaches the brain, CO2 diffuses across the blood–brain barrier into the interstitial fluid and cerebrospinal fluid that surrounds the medulla.Activity 11 Reaction componentsAllow about 10 minutesPart 1Enter the components represented by x and y that complete the formula below.x + CO_2 \rightleftharpoons H_2CO_3 \rightleftharpoons y + HCO_3 \ ^-There are superscript and subscript buttons in the formatting bar. Make sure to use these to enter the correct chemical formula, including the associated positive and negative charges:
x =
y =
x = H_2Oy = H^+giving:H_2O + CO_2 \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3 \ ^-Part 2Using the completed formula above, what will happen to levels of H+ in the brain as CO2-rich blood reaches the medulla?levels of H+ will increaselevels of H+ will decreaselevels of H+ will stay the sameAdding more CO2 will increase the production of H+ and HCO3−. Increased H+ will make the tissue more acidic, meaning that the pH will decrease.Neurons within the medullary and pontine respiratory centres will fire action potentials in response to the change in pH, via activation of receptors that are sensitive to protons (Guyenet and Bayliss, 2015). These neurons synapse onto the phrenic and intercostal nerves which innervate the diaphragm and intercostal muscles (see Section 1.2) and stimulate increased breathing (Figure 16).As the pH returns to homeostatic levels, the chemoreceptors stop being activated and the breathing rate returns to normal. Therefore, the respiratory centres act as the ‘pacemakers’ of respiration during both resting and stimulated conditions, via communication with the muscles that control the expansion and contraction of the lungs (McKay et al., 2003). Fine-tuning of the breathing pattern is controlled by inputs from the pontine respiratory group (Figure 16). Information from stretch receptors in the lungs is also used by the respiratory centres to determine when the lungs have expanded to full capacity.Some neurodegenerative diseases, such as motor neurone disease, are characterised by respiratory problems that are caused by the gradual loss of innervation to the diaphragm and intercostal muscles, despite the fact that the respiratory centres are intact. In other cases, when the respiratory centres of the medulla are damaged, individuals may require artificial ventilation of the lungs to regulate their breathing rate.6.2 Peripheral chemoreceptorsBefore the blood reaches the chemoreceptors in the brain, changes in PO2 are detected by specialised cells – called type 1 glomus cells – that are located in the carotid artery (carotid bodies) and aorta (aortic bodies) of the heart.Glomus cells are derived from the same tissue as neurons and therefore have similar properties, including electrical excitability and release of neurotransmitters. The cells express O2-sensitive potassium channels; when the PO2 falls, the K+ channels close and the resting potential of the cell becomes less negative.Glomus cells release dopamine across the neuromuscular junction, which causes the postsynaptic sensory neurons to send an afferent signal to the medullary respiratory centres. The respiratory centres will then send action potentials to the phrenic and intercostal nerves to increase the respiration rate.6.3 Additional neuronal controlThe lungs also receive innervation from the autonomic nervous system (Figure 17). The sympathetic innervation originates from the thoracic portion of the spinal cord and synapses onto the bronchiolar smooth muscle. Stimulation of these nerves causes bronchodilation.Question 13 BronchodilationWhat happens to airway resistance during bronchodilation?it increasesit decreasesit stays the sameIt decreases. Dilation will increase the diameter of the bronchioles, so the resistance to airflow will decrease.In parallel, the vagus nerves (or cranial nerve X) synapse onto the bronchi and pulmonary blood vessels as part of the parasympathetic innervation. Activity of these neurons counterbalances the sympathetic response by stimulating constriction of the bronchi. Activation of these pathways is involved in the ‘fight or flight’ response.Question 14 HyperventilationSarah has a panic disorder and frequently experiences panic attacks that cause her to hyperventilate (i.e. breathe more rapidly than normal) and feel dizzy. What branch of the autonomic nervous system is activated during the panic attack?parasympatheticsympatheticentericActivation of the sympathetic nervous system will cause the bronchioles to dilate to meet the demands of increased inspiration and expiration.What will happen to the PCO2 levels in the alveoli during hyperventilation?they will dropthey will increasethey will stay the sameThey will drop. The rapid breathing causes more CO2 to be expired, so the PCO2 in the alveoli will be lower than normal.Sarah finds that if she breathes into a paper bag during hyperventilation, her breathing returns to normal more quickly than when she just waits for the attack to pass. Why do you think this is?During hyperventilation, PCO2 in the alveoli will be lower than normal. Decreased CO2, in combination with the decreased acidity of the blood, will shift the oxygen–haemoglobin dissociation curve to the left, increasing the affinity of Hb for O2 and making it harder for O2 to diffuse into the tissue (which partly explains why she feels dizzy). Breathing into a bag concentrates the gases that are breathed out, including CO2. Re-breathing the expired, concentrated CO2 will lower the pH, reduce the activity of the respiratory neurons and restore the homeostatic breathing rate. Finally, if you play a musical wind instrument, you know that some aspects of breathing can be controlled voluntarily. This ‘override’ of the autonomic breathing system involves the motor cortex, thalamus and cerebellum, which are also involved in breath control during speech and behavioural tasks that modify breathing by learning and experience.6.4 Sleep apnoeaSleep apnoea occurs when airflow is disrupted during sleep. It can arise due to abnormalities in the medullary respiratory centres that result in a failure to regulate the contraction of the diaphragm and intercostal muscles (called central apnoea).However, the most common form of sleep apnoea is caused by an obstruction of the pharynx (termed obstructive sleep apnoea) by the muscles and soft tissues in the throat, which relax during sleep. A reduction in airflow (due to increased airway resistance) is termed hypopnoea, whereas a complete blockage of airflow (interruption for more than 10 seconds) is called apnoea. Symptoms of obstructive sleep apnoea include snoring (caused by the vibration of the soft tissues in the pharynx), struggling to breathe (or cessation of breathing) during sleep, and fatigue or falling asleep in the daytime. An instance of apnoea is shown in Video 14 below.